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Archive for the ‘Stem Cell kidney Failure’ Category

COVID Drug Given to Trump Developed From Aborted Fetus Cells – Quint Fit

Saturday, October 10th, 2020

Embryonic stem cell research has been always disputed by the 2020 Republican party. In 2019, Trumps administration paused funding for government scientists to work on studies involving embryonic stem cells, affecting about $31m in research, according to Science Magazine.

Regeneron, on the other hand, doesnt consider these cells fetal tissue because the HEK-293T line of cells has been immortalized and they divide and regenerate themselves in the laboratory.

The investigational drug has been in clinical trials since June. Even though early results from a trial with around 300 non-hospitalised COVID patients showed the drug was safe and could reduce viral levels and improve symptoms, the data is yet to be peer-reviewed.

According to CNN, the treatment is not yet approved for any use from the US FDA. The company, however, is in talks for an emergency approval. Regeneron has also confirmed that it had provided the drug under a compassionate use request for President Trump from the doctors.

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Laid off from ImmunoGen, an ex-Genzyme and Shire exec heads to an ARCH upstart – Endpoints News

Saturday, October 10th, 2020

ImmunoGen CBO Blaine McKee got laid off after the company had a big Phase III failure last March, but by the time his official exit came around in December, he already landed a plum new gig. ARCH Venture Partners had tapped the longtime executive to run a biotech willing to spend a lot of cash in an area that had gone under-invested: kidney disease.

Now that biotech is emerging from stealth mode with 12 employees, $51 million in Series A funding from ARCH and UCB Venture and two new methods of directly attacking a disease and an organ that drug developers have long only tried to mitigate from the side. Theyve also got a new name: Walden Biosciences.

Its horribly served, poorly served, there hasnt been much innovation for years, McKee told Endpoints News. Were not looking to slow the progression of renal diseases, were not looking to make a modest impact on renal disease, we want to full on stop or reverse the progression of renal disease.

Although a couple recent upstarts have altered the picture, for years the majority of drugs in biotech pipelines have treated the chronic conditions that often trigger kidney diseases, CSO Alex Duncan noted. Thats been on particularly acute display over the past year, as AstraZeneca gradually rolled out what theyve billed as unprecedented data on their SGLT2 diabetes drug Farxiga. Those data showed a 40% reduction in risk of kidney progression or cardiovascular death, but that was in patients regardless of diabetes status and in some ways an outlier.

Pharma has tended to focus on, well, lets treat the diabetes and we should be able to treat the kidney disease, Duncan, a Medimmune and AstraZeneca vet who last worked at the cancer biotech Agenus, told Endpoints. Well, that hasnt happened.

McKee, a longtime Genzyme executive who ran corporate development for Shire before the Takeda buyout, will direct a platform culled from the labs of Jochen Reiser and Sanja Sever at Massachusetts General Hospital and Harvard. Although they have yet to nominate lead candidates, their approach can be split into two different biological mechanisms.

In one path, theyll look to target a protein known as soluble urokinase plasminogen activator receptor, or simply: suPAR. Researchers have known for years that the protein, when overproduced elsewhere in the body, can flow through the blood and cause harmful inflammation in the kidney. Theyve subsequently largely used it as a biomarker. But Walden says they can use antibodies to basically neutralize suPARs before they reach the kidney, returning it to normal levels an approach akin to the antibodies now being developed to neutralize SARS-CoV-2 before it enters cells.

In the second path, theyll look to activate a protein called dynamin. The protein helps support the physical structure of the kidney itself, and in a 2015 Nature Medicine paper, Sever and Reiser describe how a small molecule that continually activates the receptor can help maintain the kidneys structure and ameliorate disease in animals. The approach, Duncan said, could allow patients to keep on meds they would have discontinued because of renal side effects.

Even with the damage that might be being caused from conditions outside of the kidney, we can make the proper filtration apparatus inside, Duncan said.

As they look to push the two programs, Walden will be boosted by a key regulatory change, McKee said. The FDA in 2018 changed their guidelines to allow companies to use the reduction of protein in the urine as an acceptable endpoint for accelerated approval. That, he said, could shave off years of development time.

He said thats what helped other VCs enter the field over the last 5 years, including Third Rock with GoldFinch in 2016 and Versant with Chinook in 2019.

Theyll be looking to put their first drug into the clinic in 2022.

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Lars Jaeger: The Future is Veggie, With 3D Printing – finews.asia

Saturday, October 10th, 2020

The energy market as well as political have changed strongly in recent years. In many countries around the world, the cards on the energy mix are being reshuffled. Lars Jaeger writes in an essay for finews.first.

This article is published on finews.first, a forum for authors specialized in economic and financial topics.

The latest example is China, where President Xi Jinping announced a few days ago that his country aims to be CO2-neutral by 2060. Political decision-makers seem to have finally started on their mission to stop climate change. But is enough when politicians pay lip service?

What about our individual responsibilities for greenhouse gas emissions? What have we personally done to curb those? Many residents of industrialized countries still drive around in large cars as a matter of course, eat large quantities of meat, eat avocados from Thailand and wear T-shirts from Bangladesh. Even the corona crisis has done little to change us from wanting to take airplanes not only for our summer vacations but increasingly also for our spring and fall vacation.

Animal husbandry accounts for a particularly large proportion of the emissions

A significant amount of greenhouse gases emission is also caused by our food consumption. What we eat is cultivated, harvested, transported, stored, processed, before it finally ends up on the market and is then consumed by us, again after storage, cooling, and preparation.

Animal husbandry accounts for a particularly large proportion of the emissions. According to the Food and Agriculture Organization of the United Nations (FAO) the keeping and processing of animals account for almost 15 percent of greenhouse gas emissions worldwide. Estimates for total food production go up to 30 percent.

To produce one kilogram of beef (approx. 2,500 kcal nutritional value) the greenhouse effective equivalent of approx. 13 kilograms of CO2 is emitted, one kilo of butter (approx. 7,000 kcal nutritional value) even comes to 24 kilograms of CO2, one kilo of lamb (approx. 3,000 kcal nutritional value) to no less than 39 kg CO2, cheese (approx. 3,000 kcal nutritional value) to an average of 8.5 kilograms of CO2 per kilo. For potatoes (approx. 860 kcal nutritional value) this value stands at just 0.4 kilograms of CO2, and the production of one kilo of fresh vegetables (approx. 400 kcal nutritional value) produces on average only 0.15 kilo CO2. Vegetables, therefore, have the best CO2 balance among the basic foodstuffs.

Transportation and packaging of the finished food products play a rather minor role in the environment

Here, methods of genetic engineering, even if they are controversial in Europe, could bring further improvements. For example, there is genetically modified rice, the production of which emits fewer greenhouse gases and which at the same time yields more. The prerequisite for this is that behind these methods stands not only the greed of companies for profit, but that they are also proven by nutritional scientists to be perfectly beneficial to our health and by environmental experts to be not harmful to the biosphere.

Transportation and packaging of the finished food products play a rather minor role in the environment (as long as they are not transported by air). Relying on regional products alone only improves the food footprint by about 4 percent (some products can even be produced overseas at lower CO2 emissions). It is more important to pay attention to seasonal foods: Apples that are stored for months in cold stores are far from being as good as fresh apples in terms of their climate balance. After six months, the energy required for cooling amounts to about 22 percent of the total energy input.

According to the WWF, the CO2 footprint of a Central Europeans diet is reduced by around 25 percent if he or she switches to a vegetarian diet. With a vegan diet, it is even 40 percent. No wonder that the Intergovernmental Panel on Climate Change (IPCC) in its Special Report on Climate Change and Land Systems of August 2019 calls for a radical change in human meat consumption. In order to feed the growing world population, we need further improved methods of food production. We simply can no longer afford to keep animals for 10 billion people.

Will we there have to do without our steak or chops in the future?

In addition, it has been well-known for a long time that meat consumption, in particular that of processed meat, is not necessarily health-promoting. It significantly increases the risk of developing colon cancer (because of the proliferation of potentially aggressive bacteria in the microbiome, the bacterial intestinal flora, which causes inflammation and cells to mutate), as well as pancreatic and prostate cancer. Further consequences of heavy meat-eating are diabetes, cardiovascular diseases, kidney failure, chronic inflammation, arthrosis and rheumatism, doctors, therefore, advise reduced meat consumption.

Will we there have to do without our steak or chops in the future? No, because also in food production we will experience dramatic technological changes. They will enable us to eat healthier and more ecological food which will at the same time be tastier than what we eat today.

The production of artificial meat in the laboratory reduces greenhouse gas emissions by up to 95 percent

Food is really just a combination of protein, fat and carbohydrates plus vitamins and trace elements. These can also be put together technically with suitable processes, and this even more efficient and nutritionally more valuable than nature does. In addition, its creation in sterile cell cultures is much more suitable for industrial meat production, because it is easier to control pathogens and toxins. In addition, the time-consuming and appetizing removal of offal, hair and bones is no longer necessary. The fat content of the meat can also be controlled. And last but not least: The production of artificial meat in the laboratory reduces greenhouse gas emissions by up to 95 percent.

As early as 2013 scientists at Maastricht University produced an artificial meatball. They took muscle stem cells from cattle, mixed those with nutrients, salts, pH buffers and growth factors and left them to reproduce. The cells became cell strands, about 20,000 of which were needed for a 140-gram meatball. Almost like meat, not quite as juicy, but the consistency is perfect, test eaters commented. The effort for this prototype was immense, however, the meatball cost 250,000 euros.

Seven years later, in-vitro meat is almost ready for the market. Appropriate 3D bio-printers serially assemble the cultured cell strands into muscle tissue. In 2020, prices were around 8 to 10 euros per burger (about 140 grams). Today, a number of start-ups are striving to bring their products to market soon at competitive prices.

Farms are also significant virus spinners

Anyone who thinks that artificially produced in-vitro meat is not very appetizing or that a diet of artificially produced meat would take people too far away from nature should spend a few hours in a large slaughterhouse or watch a large agricultural producer.

In the summer of 2020 with the Tnnies crisis in Germany, we became involuntary witnesses of the terrible conditions of todays industrial meat production. The mass production of animals in todays large farms is hardly more appetizing.

Next to wild animals, farms are also significant virus spinners. And the monocultures of todays plant food production, including those for animal feed, are coming with such massive damage to nature (soil compaction, soil erosion, fertilizers and pesticides in the groundwater, bee deaths due to pesticides) that the call for an agricultural turnaround is becoming ever louder. Instead of being a step away from nature, artificial meat production is a powerful step for its protection, i.e. a step towards nature!

Diet becomes healthier without having to sacrifice taste

And as far as palatability is concerned, probably the most important criterion for what we eat, apart from health, the alternative meat producers work together with gourmet chefs and butchers, but also with food technicians, taste experts and manufacturers of flavors and fragrances to optimize juiciness, texture and mouthfeel. Their aim is to simulate the taste of the steak deceptively realistically and by adding appropriate flavors even improve it. First testers unanimously certify that the printed steaks taste like real meat, tasty, firm to the bite and fibrous like the original.

The food market is facing a revolution. Plant food stands up quite favorably in terms of climate balance, in contrast to meat from animal production. Meat and seafood grown from cells and printed by 3D printers will dramatically reduce industrial animal husbandry and even increase our gourmet pleasure. It is estimated that by 2040 35 percent of all meat will be produced in this way.

The popular German philosopher Richard David Precht already paints the picture of a society without livestock farming, but with meat that we print out ourselves instead of it coming from pasture. In this way, we ensure the nutrition of the growing world population and reduce the ecological footprint of our diet. At the same time, our diet becomes healthier without having to sacrifice taste.

Lars Jaeger is a Swiss-German author and investment manager. He writes on the history and philosophy of science and technology and has in the past been an author on hedge funds, quantitative investing, and risk management.

Previous contributions: Rudi Bogni, Peter Kurer, Rolf Banz, Dieter Ruloff, Werner Vogt, Walter Wittmann, Alfred Mettler, Robert Holzach, Craig Murray, David Zollinger, Arthur Bolliger, Beat Kappeler, Chris Rowe, Stefan Gerlach, Marc Lussy, Nuno Fernandes, Richard Egger, Maurice Pedergnana, Marco Bargel, Steve Hanke, Urs Schoettli, Ursula Finsterwald, Stefan Kreuzkamp, Oliver Bussmann, Michael Benz, Albert Steck, Martin Dahinden, Thomas Fedier, Alfred Mettler,Brigitte Strebel, Mirjam Staub-Bisang, Nicolas Roth, Thorsten Polleit, Kim Iskyan, Stephen Dover, Denise Kenyon-Rouvinez, Christian Dreyer, Kinan Khadam-Al-Jame, Robert Hemmi,Anton Affentranger,Yves Mirabaud, Katharina Bart, Frdric Papp, Hans-Martin Kraus, Gerard Guerdat, MarioBassi, Stephen Thariyan, Dan Steinbock, Rino Borini,Bert Flossbach, Michael Hasenstab, Guido Schilling, Werner E. Rutsch,Dorte Bech Vizard, Adriano B. Lucatelli, Katharina Bart, Maya Bhandari, Jean Tirole, Hans Jakob Roth,Marco Martinelli, Thomas Sutter,Tom King,Werner Peyer, Thomas Kupfer, Peter Kurer,Arturo Bris,Frederic Papp,James Syme, DennisLarsen, Bernd Kramer, Ralph Ebert, Armin Jans,Nicolas Roth, Hans Ulrich Jost, Patrick Hunger, Fabrizio Quirighetti,Claire Shaw, Peter Fanconi,Alex Wolf, Dan Steinbock, Patrick Scheurle, Sandro Occhilupo, Will Ballard, Michael Bornhaeusser, Nicholas Yeo, Claude-Alain Margelisch, Jean-Franois Hirschel, Jens Pongratz, Samuel Gerber, Philipp Weckherlin, Anne Richards, Antoni Trenchev, Benoit Barbereau, Pascal R. Bersier, Shaul Lifshitz, Klaus Breiner, Ana Botn, Martin Gilbert, Jesper Koll, Ingo Rauser, Carlo Capaul, Claude Baumann, Markus Winkler, Konrad Hummler, Thomas Steinemann, Christina Boeck, Guillaume Compeyron, Miro Zivkovic, Alexander F. Wagner, Eric Heymann, Christoph Sax, Felix Brem, Jochen Moebert, Jacques-Aurlien Marcireau, Ursula Finsterwald, Claudia Kraaz, Michel Longhini, Stefan Blum, Zsolt Kohalmi, Karin M. Klossek, Nicolas Ramelet, Sren Bjnness, Lamara von Albertini, Andreas Britt, Gilles Prince, Darren Willams, Salman Ahmed, Stephane Monier, and Peter van der Welle, Beat Wittmann, Ken Orchard, Christian Gast, Didier Saint-Georges, Jeffrey Bohn, Juergen Braunstein, Jeff Voegeli, Fiona Frick, Stefan Schneider, Matthias Hunn, Andreas Vetsch, Fabiana Fedeli, Marionna Wegenstein, Kim Fournais, Carole Millet, Ralph Ebert, Lars Jaeger, Swetha Ramachandran, Brigitte Kaps, Thomas Stucki, Teodoro Cocca, Neil Shearing, Claude Baumann, Guy de Blonay, Tom Naratil, Oliver Berger, Robert Sharps, Tobias Mueller, Florian Wicki, Jean Keller, Fabrizio Pagani, Niels Lan Doky, Michael Welti, Karin M. Klossek, Ralph Ebert, Johnny El Hachem, Judith Basad, Katharina Bart, Thorsten Polleit, Beat Wittmann,Bernardo Brunschwiler, Peter Schmid, Karam Hinduja, Stuart Dunbar, Zsolt Kohalmi, Lars Jaeger, Raphal Surber, Santosh Brivio, Grard Piasko, Mark Urquhart, Olivier Kessler, Bruno Capone, and Peter Hody.

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5 Deadly Pre-existing Conditions You Could Have Due To COVID-19 – Brumpost – Brumpost

Saturday, October 10th, 2020

The COVID-19 is a respiratory disease caused by SARS-COV-2 virus which is a strain of virus that came from Wuhan in China late December of the year 2019 and has caused a devastating effect on almost everyone on earth forcing businesses to be closed, events to be canceled and economies to be completely shattered since its spread earlier this year 2020.

This is a very new disease and because of that, there is much to learn about the disease which scientists ae constantly working on in order to understand more about it so as to be able to fight it even much more efficiently. Meanwhile in their researches, scientists have been able to realize the roles played by pre-existing conditions in determining the severity of the disease on patients who contracts the coronavirus.

In order to assess the situations which can determine the fatality of the coronavirus infection, scientists have been able to further carry out much more researchers on pre-existing conditions which can cause serious complications.

The research was recently carried out by Penn State University which published in the journal PLOS One took a look at a variety of pre-existing conditions.

A team of researchers reviewed data on almost 500 COVID-19 cases and determined the following five cases are the deadliest pre-existing conditions when it comes to the coronavirus disease.

While an early diagnose of cancer might mean catching the malignant cells when theyre still fresh out, the American Cancer Society writes that doctors are still learning about the possible risks of COVID-19 infection for cancer patients.

The body further warned that all patients who are undergoing chemotherapy or stem cell (bone marrow) treatments should be extra careful and avoid infections at all cost because their immune system can be severely weakened by the treatment.

And for more specific information on cancer and coronavirus, be aware thatThis Type of Cancer Increases Your Risk of Severe COVID by 60 Percent.

While some diabetes can be lifelong, having the illness doesnt mean youre susceptible to catching the COVID-19 but the problem people with diabetes face is primarily a problem of worse outcomes stated the American Diabetes Association.

If your diabetes is being manage safely and regularly that puts you in a much better position but if the blood sugar level are constantly fluctuating or other diabetes-related complications can happen.

Since COVID-19 is a viral disease, this makes it also risky for diabetic patients as it can cause inflammation or internal swelling which is an already risky situation of above-target blood sugars.

Viruses also make patients more likely to experiencediabetic ketoacidosis(DKA). And if youre concerned about this condition,This Quick Trick Can Determine Your Diabetes Risk, Study Says.

Having a high blood pressure can be risky to your lifestyle causing stress and doctors have described this as the silent killer because it can often be present with no symptoms at all.

Meanwhile, early analysis of data from the outbreak of COVID-19 both in the US and China showed that having high blood pressure is the most commonly shared pre-existing condition among those hospitalized with 3- to 50 percent of patients havign it.

Hypertension is very deadly as it can weaken the patients immune system and because of this, patients hit by the COVID-19 are likely to exhibit more severe symptoms.

Patients with congestive heart failure which is a progressive, chronic weakening of the heart which causes the ventricles to lose their strength and their ability to pump sufficient blood throughout the body are 2.03 times more likely to die from COVID-19.

Studies carried out in China suggested that about 20% of the COVID-19 patients in Wuhan which is the epicenter of the original outbreak in December demonstrated a cardiac effect called myocardial injury.

However, analysis by the University of Oxford also stresses that its important thatheart failure patientsare not written off. For patients with known heart failure, continuation of current therapy is crucial, the experts warn.

Those who are constant smokers as well as older people or those living with obesity and diabetes are at a much more higher risk for chronic kidney disease and this disease also runs as an heredity which is more common in African-Americans, Native Americans and Asian-Americans.

COVID aside, chronic kidney disease is especially dangerous as it doesnt cause any symptoms untilmost of your kidney is destroyed.

As many cases of COVID-19 is being reported, patients with this disease are much more vulnerable and can lead to fatal severity if they contract the COVID-19.

Patients with chronic kidney disease (CKD) have ahigher rate of all-type infectionsand cardiovascular disease than the general population, a June paper in theClinical Kidney Journalsums up. A markedly altered immune system and immunosuppressed state may predispose CKD patients to infectious complications. Likewise, they have a state of chronic systemic inflammation that may increase their morbidity and mortality. This research found that the risk for severe COVID-19 is three times higher in those with CKD than those without it.

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The Crypto Daily Movers and Shakers October 10th, 2020 – Sports Grind Entertainment

Saturday, October 10th, 2020

Photograph: Rex/Shutterstock

Rebekah Powers was 11 when members of her faith group, the People of Praise, gathered around as she sat on a chair and laid their hands on her to pray. Powers sister had shown a gift for speaking in tongues, a defining trait of the followers of the small charismatic Christian community, and Rebekah was expected to do the same.

Related: McConnell hits out at Guardian and other media over Amy Coney Barrett scrutiny

But after what seemed like an eternity, she proved unable to produce a sound.

I couldnt get it, and I stayed there an hour and a half before they gave up and finally said, You just have blockage. You need to just work on your sin and be more open, she said.

The 41-year-old had a rebellious spirit and left People of Praise when she turned 18. It has taken decades of therapy and hard work to overcome the intense feelings of shame and fear of damnation that she said marked her childhood. The Christian faith group, based in South Bend, Indiana, dominated every aspect of her early life, she said.

Next week, Amy Coney Barrett, a conservative appellate court judge who is a prominent member of the 1,700-member strong People of Praise, will sit before the Senate judiciary committee to face questions about her judicial philosophy as part of her controversial confirmation to take a seat on the supreme court. A successful appointment, replacing the liberal Ruth Bader Ginsburg, will cement a conservative dominance on the powerful body.

Democrats have already stated that neither Barretts Catholic faith nor her membership in the People of Praise which has never publicly been discussed or disclosed, but has been examined in press reports will be raised in their questioning of the nominee.

Mitch McConnell, the Senate majority leader who is seeking to confirm Barrett before the end of October, has nevertheless said that media reports and some remarks by senators about a newly discovered public statement by Barrett in opposition to Roe v Wade, were disgusting attacks on faith. He said they risked a return to the tropes of the 1960s, when it was feared by some anti-Catholic bigots that John F Kennedy would act in the interest of the pope instead of the US.

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Our coastal elites are so disconnected from their own country that they treat religious Americans like strange animals in a menagerie, McConnell said in a statement.

But Powers, who is one of a handful of former People of Praise members who contacted the Guardian to describe their difficult experience in the group (using her married name), and some religious scholars who have studied charismatic Christian communities, say Barretts membership in this specific religious community does raise legitimate questions. They want to examine how views that are integral to the groups core beliefs from its treatment of women to the separation of church and state might influence her. They are also distinct from most mainstream Catholic faith.

In the bi-weekly and hours-long meetings that defined Powers childhood, intense prayer and discussions centered on obedience and driving out sin. Powers, who does not know Barrett, frequently witnessed people speaking in tongues and frenzied calls for evil spirits to be expelled, episodes that usually led to exorcisms.

The brainwashing and the groupthink, the female subjugation it was so devaluing

Rebekah Powers

In the strict hierarchy exercised by the group, Powers parents were often asked to take in other members into their home, even though her own family were using food stamps to get by. As a child and teenager, Powers father served as her spiritual head and worked multiple jobs, including being asked to tend to the lawns of the communitys properties, free of charge.

Women who are married, like Barrett, count their husbands as their heads.

We were Catholic, but the Catholicism was on the side. Our life, all of our friends, all of the randoms who were living in our household, were the [People of Praise] community. It was God, she said. The brainwashing and the groupthink, the female subjugation of being there to serve and listen to your spiritual head. It was so devaluing. To me, it instilled such problems.

Powers experiences are in line with a handbook called The Spirit and Purpose of the People of Praise, which was obtained by the Guardian and confirms that people who seek to be members of the group are prayed with for the release of charismatic gifts specifically, speaking in tongues and the gift of prophecy. It also states: Obedience to authority and submission to headship are active responses to the gifts of God.

Although Barrett has not discussed the issue, there is evidence that the former Notre Dame law professor served as a trustee for a school affiliated with the group; lived in the home of a prominent co-founder when she was in law school; and announced the birth of her children in People of Praises magazine, which has removed references to Barrett and her family since she joined the federal bench in 2017.

The Washington Post reported this week that Barrett served as a handmaid as late as 2010, a leadership position for women in the community, according to a directory.

Barretts father, Mike Coney, who has served in a leadership position in the People of Praise, described his own decision to join the group in a 2018 testimonial at his Catholic church, describing how he had initially unwillingly attended a charismatic seminar as a young man. When prayed with for a greater outpouring of the Holy Spirit, nothing happened. Then later that night I began to speak in tongues. More importantly, I was filled with an insatiable appetite for reading scripture and spiritual books, he wrote.

Thomas Csordas, an anthropology professor at the University of California San Diego who has studied the issues around communities like People of Praise, said it was wrong to focus attention on whether the group could be a considered a cult in the spirit of Jim Joness Peoples Temple. It was much more appropriate, he said, to examine what he called the intentional community of People of Praise and its nature of being conservative, authoritarian, hierarchical, and patriarchal.

I think theyre potentially more dangerous and much more sophisticated [than a cult], he said. It is not the kind of group where submission of women to men means that they have to stay barefoot and pregnant. Instead, they have to be lawyers and judges and submissive to men at the same time. They have to be able to have a career and seven kids at the same time.

Far from taking her cues from the People of Praise, Csordas said, Barretts biography showed she was not a mindless devotee of a cult, but rather part of the elite of the intentional charismatic covenant community, reflecting her previous status as a handmaiden and trustee of the school, and her fathers leadership role.

Related: Revealed: Amy Coney Barrett lived in home of secretive Christian groups co-founder

Contrary to a situation in which people might worry she might be told what to think or told by her husband. Being that far into the community means, no, she is going to be teaching other people. She already knows what to think because of the patriarchal structure she was raised in, which mirrors conservative Catholic views and the views of her judicial mentor, Antonin Scalia.

Massimo Faggioli, a professor of theology at Villanova University, said that even if senators declined to question Barrett about her faith, the issues deserved to be aired in other forums because groups like People of Praise, he said, does reject a secular view of separation between church and state.

I dont think we should put her Catholicism on trial, but the Catholic conservative legal movement is putting liberalism on trial. They want to change a certain understanding of the liberal order of individual rights, and that is coming from the religious worldview of Catholic groups, he said.

Maybe not in the Senate, but in the public square.

A spokesman for People of Praise has said it would be inappropriate to discuss Barrett. He has also said the organization is an ecumenical community that strives to allow men and women with a wide variety of political and religious views to live together in harmony.

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Coronavirus Tracker: Bexar Co. cases surpass 59,000; Texas hospitalizations trending in the wrong direction – KENS5.com

Saturday, October 10th, 2020

Facts, not fear: KENS 5 is tracking the latest numbers from the coronavirus (COVID-19) pandemic in San Antonio and across Texas.

SAN ANTONIO We're tracking the latest numbers from the coronavirus pandemic in San Antonio and across Texas. Here are the latest numbers reported by Bexar and surrounding counties:

How Bexar County is trending

We've tracked how many coronavirus cases have been confirmed in Bexar County from the time officials began reporting cases in March 2020. The graphic below shows the number of cases since June and charts those daily case numbers along a 7-day moving average to provide a more accurate picture of the overall coronavirus case curve in our area and the direction we're trending amid the pandemic.

On Wednesday, San Antonio Mayor Ron Nirenberg announced 214 additional coronavirus cases in Bexar County, sending the local total over 59,000. In all, 59,153 residents have been diagnosed with COVID-19.

Nirenberg also said there were no additional virus-related deaths in the county. In all, 1,168 county residents have died from coronavirus complications.

Hospitalizations in the county dropped ever so slightly on Wednesday. 203 residents were receiving treatment for coronavirus symptoms, which is three fewer than on Tuesday. And the number of patients using ventilators (39) and in ICU (84) are also slight drops from Tuesday's numbers.

Coronavirus in Texas

The number of Texans who have tested positive for the coronavirus since the pandemic began grew by 4,121 cases on Wednesday, according to the Texas Department of State Health Services.

3,776 of those are new diagnoses over the last 24 hours, while the other 345 cases stem from a number of backlogs in several counties and groups of previously unreported cases in some areas. More details can be found at the top of this page.

In total, 777,556 coronavirus cases have been confirmed in Texas.

State health authorities, meanwhile, reported an additional 119 virus-related deaths on Wednesday. At least 16,230 Texans have passed away from COVID-19 complications.

The state also saw a sharp uptick in hospitalizations on Wednesday. There were 125 more Texans receiving treatment for coronavirus symptoms in the last 24 hours, for a total of 3,519 currently hospitalized; it's been nearly a month since the figure was that high.

The state estimates that 692,123 Texans have recovered, while 70,813 Texans remain ill with COVID-19.

Meanwhile, the Texas Education Agency updated its online coronavirus database to show that there have been 9,857 cumulative cases among staff and students across the state as of Sept. 27. More information can be found here.

Latest Coronavirus Headlines

Coronavirus symptoms

The symptoms of coronavirus can be similar to the flu or a bad cold. Symptoms include fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell sore throat, congestion or runny nose, nausea or vomiting and diarrhea, according to the Centers for Disease Control.

Most healthy people will have mild symptoms. A study of more than 72,000 patients by the Centers for Disease Control in China showed 80 percent of the cases there were mild.

But infections can cause pneumonia, severe acute respiratory syndrome, kidney failure, and even death, according to the World Health Organization. Older people with underlying health conditions are most at risk.

But infections can cause pneumonia, severe acute respiratory syndrome, kidney failure, and even death, according to the World Health Organization. Older people with underlying health conditions are most at risk.

Experts determined there was consistent evidence these conditions increase a person's risk, regardless of age:

The CDC believes symptoms may appear anywhere from two to 14 days after being exposed.

Human coronaviruses are usually spread...

Help stop the spread of coronavirus

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Ligand Announces its Captisol Business is Positioned for Major Growth and Forecasts 2021 Captisol Material Sales of $200 Million – Business Wire

Thursday, September 24th, 2020

SAN DIEGO--(BUSINESS WIRE)--Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces that recent new contracting with partners and investments in manufacturing capacity have contributed to its Captisol business operating at the highest levels in the history of the technology and position Captisol for major growth. Significant new clinical and regulatory developments with Evomela and Kyprolis, among other drugs, are reinforcing the role the proprietary technology serves in enabling important medicines. During 2020, Ligand has facilitated the successful installation of equipment to allow production at significantly higher levels to support anticipated demand. In addition to manufacturing at partner Hoviones facilities in Ireland and Portugal, Ligand has now added final step processing capacity for Captisol in both the United States and England. Ligand also introduces guidance for 2021 Captisol material sales of approximately $200 million.

The global medical need for Captisol-enabled drugs has never been higher, said John Higgins, Chief Executive Officer of Ligand. Our recently expanded operating team has successfully positioned our Captisol technology for the substantial growth we now expect in 2021 and beyond. There is significant ongoing investment by our partners for over 30 Captisol-enabled medicines in clinical development. We have entered into more contracts this year than any other year and are proud to be working closely with Gilead under our recently extended 10-year supply contract. We continue to be pleased with the momentum relating to Captisol, as it is a critical component in multiple life-saving medicines.

Recent Captisol technology business highlights include the following:

Ligands forecast for 2021 Captisol material sales of approximately $200 million is based on information it has on anticipated demand from its major partners given growth in existing and new markets, clinical requirements for Captisol-enabled development programs and binding orders from certain commercial or pre-commercial partners. The 2021 Captisol outlook compares with the Companys guidance for 2020 Captisol material sales of approximately $90 million.

About Captisol

Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella, University Distinguished Professor at the University of Kansas Higuchi Biosciences Center for specific use in drug development and formulation. This unique technology has enabled several FDA-approved products, including Gileads VEKLURY, Amgens KYPROLIS, Baxter Internationals NEXTERONE, Acrotech Biopharma L.L.C.s and CASI Pharmaceuticals EVOMELA, Melinta Therapeutics BAXDELA and Sage Therapeutics ZULRESSO. There are many Captisol-enabled products currently in various stages of development. Ligand maintains a broad global patent portfolio for Captisol with more than 400 issued patents worldwide relating to the technology (including 37 in the U.S.) and with the latest expiration date in 2033. Other patent applications covering methods of making Captisol, if issued, extend to 2040.

About Ligand Pharmaceuticals

Ligand is a revenue-generating biopharmaceutical company focused on developing or acquiring technologies that help pharmaceutical companies discover and develop medicines. Our business model creates value for stockholders by providing a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable, diversified and lower-risk business than a typical biotech company. Our business model is based on doing what we do best: drug discovery, early-stage drug development, product reformulation and partnering. We partner with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) to ultimately generate our revenue. Ligands OmniAb technology platform is a patent-protected transgenic animal platform used in the discovery of fully human mono- and bispecific therapeutic antibodies. The Captisol platform technology is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. The Vernalis Design Platform (VDP) integrates protein structure determination and engineering, fragment screening and molecular modeling, with medicinal chemistry, to help enable success in novel drug discovery programs against highly challenging targets. Ab Initio technology and services for the design and preparation of customized antigens enable the successful discovery of therapeutic antibodies against difficult-to-access cellular targets. Icagen has established deep biological expertise focused on ion channels and transporters and has a strong track record in ion channel drug discovery from screening to lead optimization. Ligand has established multiple alliances, licenses and other business relationships with the worlds leading pharmaceutical companies including Amgen, Merck, Pfizer, Sanofi, Janssen, Takeda, Servier, Gilead Sciences and Baxter International. For more information, please visit http://www.ligand.com.

Follow Ligand on Twitter @Ligand_LGND.

Forward-Looking Statements

This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Words such as plans, believes, expects, anticipates, and will, and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding: Ligands expectation that Captisol demand will increase significantly in 2021 and beyond (particularly for sales to Gilead and to partners in Gileads consortium) and Ligands ability to supply Captisol to Gilead and other partners, including Ligands ability to increase supply capacity; the timing of initiation, enrollment and expected results with respect to the planned clinical trial of CE-Iohexol; and guidance regarding Ligands 2020 and 2021 Captisol material sales. Actual events or results may differ from Ligand's expectations due to risks and uncertainties inherent in Ligands business, including, without limitation: Ligand may not receive expected revenue from Captisol sales; the COVID-19 pandemic has disrupted Ligands and its partners business, including delaying manufacturing, preclinical studies and clinical trials and product sales, and impairing global economic activity, all of which could materially and adversely impact Ligands results of operations and financial condition; Ligand may not achieve its Captisol material sales guidance for 2020 and/or 2021; remdesivir may be later shown to not be effective or safe for the treatment of COVID-19 and/or the FDA (and/or equivalent agencies in other countries) may revise or revoke its emergency use authorization for remdesivir for the treatment of COVID-19 in patients hospitalized with moderate or severe disease if the FDA (and/or another such agency) determines that authorization no longer meets the statutory criteria for issuance; alternative COVID-19 therapies or vaccines may be approved or the risk of coronavirus infection could significantly diminish, any of which could materially and adversely affect the commercial opportunity for remdesivir; Gilead may terminate the supply agreement without cause upon 30 days prior written notice; Ligand may be unable to scale-up the supply of Captisol or at acceptable prices; Ligand is currently dependent on Hovione as a single source sole supplier for certain Captisol manufacturing functions and failures by such supplier may result in delays or inability to meet the Captisol demands of its partners; Amgen, Acrotech Biopharma or other Ligand partners may not execute on their sales and marketing plans for marketed products for which Ligand has an economic interest; Ligand or its Captisol partners may not be able to protect their intellectual property and patents covering certain products and technologies may be challenged or invalidated; Ligand's Captisol partners may terminate agreements or development or commercialization of products; Ligand may not generate expected revenues under its existing license agreements and may experience significant costs as the result of potential delays under its supply agreements; Ligand and its Captisol partners may experience delays in the commencement, enrollment, completion or analysis of clinical testing for product candidates, or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, which could result in increased costs and delays, or limit the ability to obtain regulatory approval; unexpected adverse side effects or inadequate therapeutic efficacy of Ligand's or its Captisol partners product(s) could delay or prevent regulatory approval or commercialization; and ongoing or future litigation could expose Ligand to significant liabilities and have a material adverse effect on the company. The failure to meet expectations with respect to any of the foregoing matters may reduce Ligand's stock price. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases available at http://www.ligand.com as well as in Ligand's public periodic filings with the Securities and Exchange Commission available at http://www.sec.gov. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

a Monahan, et al. Biology of Blood and Marrow Transplantation, September 2020

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Ligand Announces its Captisol Business is Positioned for Major Growth and Forecasts 2021 Captisol Material Sales of $200 Million - Business Wire

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Seattle Genetics and Merck Announce Two Strategic Oncology Collaborations – BioSpace

Tuesday, September 15th, 2020

Sept. 14, 2020 10:45 UTC

BOTHELL, Wash. & KENILWORTH, N.J.--(BUSINESS WIRE)-- Seattle Genetics, Inc. (Nasdaq: SGEN) and Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced two new strategic oncology collaborations.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200914005237/en/

The companies will globally develop and commercialize Seattle Genetics ladiratuzumab vedotin, an investigational antibody-drug conjugate (ADC) targeting LIV-1, which is currently in phase 2 clinical trials for breast cancer and other solid tumors. The collaboration will pursue a broad joint development program evaluating ladiratuzumab vedotin as monotherapy and in combination with Mercks anti-PD-1 therapy KEYTRUDA (pembrolizumab) in triple-negative breast cancer, hormone receptor-positive breast cancer and other LIV-1-expressing solid tumors. Under the terms of the agreement, Seattle Genetics will receive a $600 million upfront payment and Merck will make a $1.0 billion equity investment in 5.0 million shares of Seattle Genetics common stock at a price of $200 per share. In addition, Seattle Genetics is eligible for progress-dependent milestone payments of up to $2.6 billion.

Separately, Seattle Genetics has granted Merck an exclusive license to commercialize TUKYSA (tucatinib), a small molecule tyrosine kinase inhibitor, for the treatment of HER2-positive cancers, in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. Seattle Genetics will receive $125 million from Merck as an upfront payment and is eligible for progress-dependent milestones of up to $65 million.

Collaborating with Merck on ladiratuzumab vedotin will allow us to accelerate and broaden its development program in breast cancer and other solid tumors, including in combination with Mercks KEYTRUDA, while also positioning us to leverage our U.S. and European commercial operations, said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. The strategic collaboration for TUKYSA will help us reach more patients globally and benefit from the established commercial strength of one of the worlds premier pharmaceutical companies.

These two strategic collaborations will enable us to further diversify Mercks broad oncology portfolio and pipeline, and to continue our efforts to extend and improve the lives of as many patients with cancer as possible, said Dr. Roger M. Perlmutter, President, Merck Research Laboratories. We look forward to working with the team at Seattle Genetics to advance the clinical program for ladiratuzumab vedotin, which has shown compelling signals of efficacy in early studies, and to bring TUKYSA to even more patients with cancer around the world.

Ladiratuzumab Vedotin Collaboration Details

Under the terms of the agreement, Seattle Genetics and Merck will collaborate and equally share costs on the global development of ladiratuzumab vedotin and other LIV-1-targeting ADCs. The companies have agreed to jointly develop and share future costs and profits for ladiratuzumab vedotin on a 50:50 basis worldwide. Merck will pay Seattle Genetics $600 million upfront and make a $1.0 billion equity investment in 5.0 million shares of Seattle Genetics common stock at a price of $200 per share. In addition, Seattle Genetics will be eligible to receive up to $2.6 billion in milestone payments, including $850 million in development milestones and $1.75 billion in sales milestones.

The companies will jointly develop and commercialize ladiratuzumab vedotin and equally share profits worldwide. The companies will co-commercialize in the U.S. and Europe. Seattle Genetics will be responsible for marketing applications for approval in the U.S. and Canada, and will record sales in the U.S., Canada and Europe. Merck will be responsible for marketing applications for approval in Europe and in countries outside the U.S. and Canada, and will record sales in countries outside the U.S., Europe and Canada. Including the upfront payment, equity investment proceeds and potential milestone payments, Seattle Genetics is eligible to receive up to $4.2 billion.

The closing of the equity investment is contingent on completion of review under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act).

TUKYSA Collaboration Details

Under the terms of the agreement, Merck has been granted exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. Seattle Genetics retains commercial rights and will record sales in the U.S., Canada and Europe. Merck will be responsible for marketing applications for approval in its territory, supported by the positive results from the HER2CLIMB clinical trial.

Merck will also co-fund a portion of the TUKYSA global development plan, which encompasses several ongoing and planned trials across HER2-positive cancers, including breast, colorectal, gastric and other cancers set forth in a global product development plan. Seattle Genetics will continue to lead ongoing TUKYSA global development planning and operational execution. Merck will solely fund and conduct country-specific clinical trials necessary to support anticipated regulatory applications in its territory.

Seattle Genetics will receive from Merck $125 million as an upfront payment and is eligible to receive progress-dependent milestones of up to $65 million. Seattle Genetics will also receive $85 million in prepaid research and development payments to be applied to Mercks global development funding obligations. In addition, Seattle Genetics would receive tiered royalties on sales of TUKYSA in Mercks territory.

The financial impact of these collaborations is not included in Seattle Genetics 2020 guidance.

Seattle Genetics Conference Call Details

Seattle Genetics management will host a conference call to discuss these collaborations today at 6:00 a.m. Pacific Time (PT); 9:00 a.m. Eastern Time (ET). The event will be simultaneously webcast and available for replay from the Seattle Genetics website at http://www.seattlegenetics.com, under the Investors section. Investors may also participate in the conference call by calling 844-763-8274 (domestic) or +1 412-717-9224 (international). The conference ID is 10147850.

About Ladiratuzumab Vedotin

Ladiratuzumab vedotin is a novel investigational ADC targeted to LIV-1. Most metastatic breast cancers express LIV-1, which also has been detected in several other cancers, including lung, head and neck, esophageal and gastric. Ladiratuzumab vedotin utilizes Seattle Genetics proprietary ADC technology and consists of a LIV-1-targeted monoclonal antibody linked to a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE) by a protease-cleavable linker. This novel ADC is designed to bind to LIV-1 on cancer cells and release the cell-killing agent into target cells upon internalization. Ladiratuzumab vedotin may also cause antitumor activity through other mechanisms, including activation of an immune response by induction of immunogenic cell death.

About TUKYSA (tucatinib)

TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth. TUKYSA in combination with trastuzumab and capecitabine was approved by the U.S. Food and Drug Administration (FDA) in April 2020 for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In addition, TUKYSA received approval in Canada, Singapore, Australia and Switzerland under the Project Orbis initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology products among international partners. A marketing application is under review in the European Union.

TUKYSA is being evaluated in several ongoing clinical trials and additional studies are planned. Current trials include the following:

For additional information, visit http://www.clinicaltrials.gov.

TUKYSA Important Safety Information

Warnings and Precautions

If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

Adverse Reactions

Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in 2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in 1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in 2% of patients were hepatotoxicity (8%) and diarrhea (6%).

The most common adverse reactions in patients who received TUKYSA (20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Lab Abnormalities

In HER2CLIMB, Grade 3 laboratory abnormalities reported in 5% of patients who received TUKYSA were: decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

Drug Interactions

Use in Specific Populations

For more information, please see the full Prescribing Information for TUKYSA here.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

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Seattle Genetics and Merck Announce Two Strategic Oncology Collaborations - BioSpace

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Alexion and Caelum Biosciences Announce Start of Phase 3 Studies of CAEL-101 in AL Amyloidosis – Business Wire

Tuesday, September 15th, 2020

BOSTON & BORDENTOWN, N.J.--(BUSINESS WIRE)--Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) and Caelum Biosciences today announced the initiation of the Cardiac Amyloid Reaching for Extended Survival (CARES) Phase 3 clinical program to evaluate CAEL-101, a first-in-class amyloid fibril targeted therapy, in combination with standard-of-care (SoC) therapy in AL amyloidosis. The CARES clinical program includes two parallel Phase 3 studies one in patients with Mayo stage IIIa disease and one in patients with Mayo stage IIIb disease and will collectively enroll approximately 370 patients globally. Enrollment is underway in both studies. The primary objective of the clinical program is to assess overall survival.

In AL amyloidosis, misfolded amyloid proteins can build up in many organs throughout the body, including the heart and kidneys, causing significant damage to these organs and impairing their function. While current treatments address the bone marrow disorder that creates the misfolded amyloid proteins, there are no approved therapies for the significant organ damage the disease causes, said John Orloff, M.D., Executive Vice President and Head of Research and Development at Alexion. CAEL-101 has the potential to be the first treatment to target and remove the amyloid deposits from these organs. Data from Phase 1 studies suggest that this treatment approach may improve organ function and long-term survival. We look forward to investigating this further in the Phase 3 clinical program.

AL amyloidosis is particularly devastating when it affects the heart, with median survival in these patients of less than one year following diagnosis, said Michael Spector, President and Chief Executive Officer of Caelum. Long-term survival data from AL amyloidosis patients treated with CAEL-101 in the Phase 1a/1b study showed that 78 percent were still alive after a median follow-up time of more than three years. We recognize the urgent need for new treatments that address the organ damage caused by AL amyloidosis and are working together with the AL amyloidosis community and Alexion to advance the Phase 3 clinical program as quickly as possible.

About the CARES Phase 3 Clinical Program

The CARES clinical program consists of two parallel double-blind, randomized, event-driven global Phase 3 studies, which are evaluating the efficacy and safety of CAEL-101 in AL amyloidosis patients who are newly diagnosed and nave to standard of care (SoC) treatment (cyclophosphamide-bortezomib-dexamethasone (CyBorD) chemotherapy). One study is enrolling approximately 260 patients with Mayo stage IIIa disease and one study is enrolling approximately 110 patients with Mayo stage IIIb disease. The studies will be conducted at approximately 70 sites across North America, the United Kingdom, Europe, Israel, Japan, and Australia.

In each study, participants are being randomized in a 2:1 ratio to receive either CAEL-101 plus SoC or placebo plus SoC once weekly for four weeks. This will be followed by a maintenance dose administered every two weeks until the last patient enrolled completes at least 50 weeks of treatment. Patients will continue follow-up visits every 12 weeks.

The primary study objectives are overall survival and the safety and tolerability of CAEL-101. Key secondary objectives will assess functional improvement in the six-minute walk test (6MWT), quality of life measures (Kansas City Cardiomyopathy Questionnaire Overall Score & Short Form 36 version 2 Physical Component Score) and cardiac improvement (Global Longitudinal Strain, or GLS).

Phase 2 Study Results

The Phase 2 open-label dose escalation study was conducted to investigate higher doses of CAEL-101 than had been evaluated in Phase 1 studies with a primary objective to identify the best dose to advance into Phase 3 development. The study evaluated the safety and tolerability of CAEL-101 in 13 AL amyloidosis patients at three study sites who received up to 1000 mg/m2 of CAEL-101 (two times the Phase 1 dose) administered in combination with SoC treatment. The study met its primary objectives, supporting the safety and tolerability of CAEL-101 and the selection of the 1000 mg/m2 dose for the Phase 3 study.

Phase 1a/1b Long-Term Follow-Up Results Presented at ISA 2020

As previously reported, the Phase 1a/1b study of CAEL-101 was the first clinical trial to demonstrate improvement in cardiac function via GLS after treatment with an amyloid fibril targeted therapy in AL amyloidosis patients with amyloid cardiac involvement. New long-term follow-up data from the Phase 1a/1b study will be presented at the virtual International Symposium on Amyloidosis (ISA), September 14 to 18, 2020, in the poster titled, Long term follow-up of patients with AL amyloidosis treated on a phase 1 study of Anti-Amyloid Monoclonal Antibody CAEL-101 (Abstract #342, Divaya Bhutani, M.D., et. al, Columbia University Medical Center). These data demonstrate 78 percent survival (15/19) at a median follow-up of more than three years (37 months) in AL amyloidosis patients treated with CAEL-101 as well as durable organ response among evaluable patients, further supporting the advancement of CAEL-101 into Phase 3 development.

About CAEL-101

CAEL-101 is a first-in-class monoclonal antibody (mAb) designed to improve organ function by reducing or eliminating amyloid deposits in the tissues and organs of patients with AL amyloidosis. The antibody is designed to bind to misfolded light chain protein and amyloid and shows binding to both kappa and lambda subtypes. In a Phase 1a/1b study, CAEL-101 demonstrated improved organ function, including cardiac and renal function, in 27 patients with relapsed and refractory AL amyloidosis who had previously not had an organ response to standard of care therapy. CAEL-101 has received Orphan Drug Designation from both the U.S. Food and Drug Administration and European Medicine Agency as a therapy for patients with AL amyloidosis.

About AL Amyloidosis

AL amyloidosis is a rare systemic disorder caused by an abnormality of plasma cells in the bone marrow. Misfolded immunoglobulin light chains produced by plasma cells aggregate and form fibrils that deposit in tissues and organs. This deposition can cause widespread and progressive organ damage and high mortality rates, with death most frequently occurring as a result of cardiac failure. Current standard of care includes plasma cell directed chemotherapy and autologous stem cell transplant, but these therapies do not address the organ dysfunction caused by amyloid deposition, and up to 80 percent of patients are ineligible for transplant.

AL amyloidosis is a rare disease but is the most common form of amyloidosis. There are approximately 22,000 patients across the United States, France, Germany, Italy, Spain and the United Kingdom. AL amyloidosis has a one-year mortality rate of 47 percent, 76 percent of which is caused by cardiac amyloidosis.

About Alexion

Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialization of life-changing medicines. As a leader in rare diseases for more than 25 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D) as well as the first and only approved Factor Xa inhibitor reversal agent. In addition, the company is developing several mid-to-late-stage therapies, including a copper-binding agent for Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain (AL) amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, metabolic disorders and cardiology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. This press release and further information about Alexion can be found at: http://www.alexion.com.

[ALXN-P]

About Caelum Biosciences

Caelum Biosciences, Inc. (Caelum) is a clinical-stage biotechnology company developing treatments for rare and life-threatening diseases. Caelums lead asset, CAEL-101, is a novel antibody for the treatment of patients with amyloid light chain (AL) amyloidosis. In 2019, Caelum entered a collaboration agreement with Alexion under which Alexion acquired a minority equity interest in Caelum and an exclusive option to acquire the remaining equity in the company based on Phase 3 CAEL-101 data. Caelum was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.caelumbio.com.

Forward-Looking Statement

This press release contains forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Alexion and Caelum, including statements related to: the safety and efficacy CAEL-101 as a treatment for AL amyloidosis; CAEL-101 has the potential to be the first treatment to target and remove the amyloid deposits from the heart, kidney and other organs; data from the Phase 1 studies suggest that the treatment approach may improve organ function and long-term survival and enrollment of the Phase 3 trials. Forward-looking statements are subject to factors that may cause Alexion's and Caelums results and plans to differ materially from those expected by these forward looking statements, including for example: the anticipated safety profile and the benefits of the CAEL-101 may not be realized (and the results of the clinical trials may not be indicative of future results); the inability to enroll and complete the Phase 3 trial; results of clinical trials may not be sufficient to satisfy regulatory authorities; results in clinical trials may not be indicative of results from later stage or larger clinical trials (or in broader patient populations); the possibility that results of clinical trials are not predictive of safety and efficacy and potency of our products (or we fail to adequately operate or manage our clinical trials) which could cause us to discontinue sales of the product (or halt trials, delay or prevent us from making regulatory approval filings or result in denial of approval of our product candidates); the severity of the impact of the COVID-19 pandemic on Alexions or Caelums business, including on commercial and clinical development programs; unexpected delays in clinical trials; unexpected concerns regarding products and product candidates that may arise from additional data or analysis obtained during clinical trials or obtained once used by patients following product approval; future product improvements may not be realized due to expense or feasibility or other factors; delays (expected or unexpected) in the time it takes regulatory agencies to review and make determinations on applications for the marketing approval of our products; inability to timely submit (or failure to submit) future applications for regulatory approval for our products and product candidates; inability to timely initiate (or failure to initiate) and complete future clinical trials due to safety issues, IRB decisions, CMC-related issues, expense or unfavorable results from earlier trials (among other reasons); future competition from biosimilars and novel products; decisions of regulatory authorities regarding the adequacy of our research, marketing approval or material limitations on the marketing of our products; delays or failure of product candidates to obtain regulatory approval; delays or the inability to launch product candidates due to regulatory restrictions, anticipated expense or other matters; interruptions or failures in the manufacture and supply of our products and our product candidates; failure to satisfactorily address matters raised by regulatory agencies regarding our products and product candidates; uncertainty of long-term success in developing, licensing or acquiring other product candidates or additional indications for existing products; the adequacy of our pharmacovigilance and drug safety reporting processes; failure to protect and enforce our data, intellectual property and proprietary rights and the risks and uncertainties relating to intellectual property claims, lawsuits and challenges against us; the risk that third party payors (including governmental agencies) will not reimburse for the use of our products at acceptable rates or at all; delay of collection or reduction in reimbursement due to adverse economic conditions or changes in government and private insurer regulations and approaches to reimbursement; adverse impacts on supply chain, clinical trials, manufacturing operations, financial results, liquidity, hospitals, pharmacies and health care systems from natural disasters and global pandemics, including COVID-19 and a variety of other risks set forth from time to time in Alexion's filings with the SEC, including but not limited to the risks discussed in Alexion's Quarterly Report on Form 10-Q for the period ended June 30, 2020 and in their other filings with the SEC. Alexion disclaims any obligation to update any of these forward-looking statements to reflect events or circumstances after the date hereof, except when a duty arises under law.

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Braunstein Reflects on the Rise of Quadruplet Therapies in Multiple Myeloma – OncLive

Wednesday, September 9th, 2020

Triplet therapies have become the accepted standard of care in multiple myeloma, according toMarc J. Braunstein, MD, PhD, who added that emerging quadruplet therapies are also generating excitement in the field.

As seen in the up-front setting, there has been an explosion of therapies, not just for patients with relapsed/refractory multiple myeloma who progress after induction therapy, but also for patients who progress after multiple lines of therapy, said Braunstein, an assistant professor in the Department of Medicine at NYU Long Island School of Medicine. In the field, we appreciate that clonal resistance is truly what leads to shorter remission over time. Now that we have more therapies to offer, we are seeing several new combinations.

In a special episode of OncLiveOn Air, Braunstein, who is also the course co-director of the Hematology-Oncology System and co-director of the Autologous Stem Cell Transplant Program at NYU Winthrop Hospital of NYU Langone Healths Perlmutter Cancer Center, highlighted pivotal research on the use of triplet and quadruplet regimens in the up-front and relapsed/refractory settings presented during the 2020 ASCO Virtual Scientific Program.

VRd Remains the Standard of Care in Newly Diagnosed Multiple Myeloma

Carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) did not improve progression-free survival (PFS) in patients with newly diagnosed multiple myeloma, according to results of the phase 3 ENDURANCE (E1A11) trial (NCT01863550).1

In the randomized analysis, investigators compared the use of KRd with that of bortezomib (Velcade), lenalidomide, and dexamethasone (VRd) in treatment-nave patients with multiple myeloma who had an ECOG performance score of 0, 1, or 2. Patients also had to have acceptable hematological parameters and organ function and measurable disease in serum, urine, or bone marrow to be included. If they had grade 2 or higher peripheral neuropathy or New York Heart Association III or IV heart failure or myocardial infarction less than 6 months before study start, they could not participate.

The first co-primary end point of the trial was PFS for the induction randomization and the second co-primary end point was overall survival (OS) for the second randomization. Key secondary end points included overall response rate, minimal residual disease negativity rate per flow cytometry, time to progression, OS, and toxicity.

In the field, this trial was patiently awaited for some time because we were eager to see the head-to-head comparison of a triplet regimen that includes either the protostome inhibitor bortezomib or carfilzomib in combination with lenalidomide and dexamethasone, the 2 most common up-front regimens in the space, explained Braunstein.

A total of 1087 patients were randomized 1:1 to receive VRd (n = 542) or KRd (n = 545). Patients on the VRd arm received 1.3 mg/m2of bortezomib on days 1, 4, 8, and 11 for cycles 1-8 and the same dose on days 1 and 8 for cycles 9-12; 25 mg of daily lenalidomide on days 1-14; and 20 mg of dexamethasone in on days 1, 2, 4, 5, 8, 9, 11, and 12 for cycles 1-4, and then 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 for cycles 5-8, followed by 10 mg on days 1, 2, 8, and 9 for cycles 9-12. Treatment cycles were repeated every 3 weeks for 12 cycles.

Patients on the KRd arm received 20 mg/m2of carfilzomib on days 1 and 2 and 36 mg/m2on days 8, 9, 15, and 16 of cycle 1 followed by 36 mg/m2on days 1, 2, 8, 9, 15, and 16 for cycles 2-9; 25 mg of lenalidomide on days 1-21, and 40 mg of dexamethasone on days 1, 8, 15, and 22 for cycles 1-4 and 20 mg on days 1, 8, 15, and 22 for cycles 5-12. This treatment cycle was repeated every 4 weeks for 9 total cycles.

Results showed a median PFS of 34.4 months (95% CI, 30.1not evaluable) in the VRd arm compared with 34.6 months (95% CI, 28.8-37.8) in the KRd arm (HR, 1.04; 95% CI, 0.83-1.31; P = .742). In addition, on the VRd arm, 21 patients (4.0%) experienced a stringent complete response (sCR), 57 (10.8%) achieved a CR, 263 had a very good partial response (VGPR), and 103 patients had a partial response (PR). On the KRd arm, 31 patients (5.9%) achieved a sCR, 65 (12.4%) had a CR, 292 patients (55.5%) experienced a VGPR, and 68 (12.9%) had a PR. The median OS from induction randomization was not yet reached in either arm.

Moreover, treatment-related adverse effects (TRAEs) were mostly grade 3-5 and consisted of peripheral neuropathy, dyspnea, hypertension, heart failure, and acute kidney injury. The TRAEs of interest were cardiac, pulmonary, and renal, as well as peripheral neuropathy.

One of the criticisms of this study is that it did not include patients with high-risk multiple myeloma who, in prior studies, showed a benefit with carfilzomib, Braunstein noted. Notably, approximately 27% of patients in each group went on to receive autologous stem cell transplant, which was not planned according to the design of the study.

Based on these data, the investigators concluded that VRd should remain the standard of care.

Isatuximab/KRd for Newly Diagnosed, High-Risk Multiple Myeloma

Isatuximab-irfc (Sarclisa) plus KRd can be safely administered in patients with high-risk multiple myeloma, inducing deep responses, according to results from the interim analysis of the GMMG-concept trial presented during the meeting; this was the first study to investigate the quadruplet regimen in this patient population.2

In the multicenter, open-label, phase 2 analysis, investigators evaluated the efficacy of isatuximab, an anti-CD38 monoclonal antibody, in combination with KRd in patients with high-risk, newly diagnosed multiple myeloma. Patients could have received up to 1 cycle of anti-myeloma treatment prior to inclusion. They had to show acceptable organ function in order to participate.

The primary end point of the trial was minimal residual disease (MRD) negativity by flow cytometry to a sensitivity of 10-5and the secondary end point was PFS. Tertiary end points included ORR, duration of MRD negativity, OS, and quality-of-life (QOL) assessment.

This was an investigator-initiated study that ultimately evaluated a quadruplet regimen, which is the trend that we are pursuing these days in terms of up-front therapy, noted Braunstein.

In the analysis, 153 patients were randomized 1:1 based on transplant eligibility. In arm A, 117 transplant-eligible patients received 6 cycles of isatuximab plus KRd induction, 4 cycles of isatuximab plus KRd consolidation, and isatuximab plus KR maintenance. In arm B, 36 transplant-ineligible patients received the same course of treatment with 2 additional cycles of isatuximab plus KRd induction.

The interim analysis reported on a total of 50 patients: 46 in arm A and 4 in arm B. Results showed an ORR of 100% with the quadruplet, a VGPR or greater of 90%, a CR/sCR of 46%. In arm A, 41 of 46 patients achieved a VGPR or greater, while all patients in arm B achieved a VGPR. MRD was assessed in a total of 33 patients in arm A during induction and results showed that 20 patients were MRD negative, 11 were MRD positive, and 2 were not evaluable.

With regard to safety, the most common hematologic treatment-emergent AEs (TEAEs) reported were grade 3 or 4 and consisted of leukopenia (26%), neutropenia (34%), lymphopenia (28%), anemia (10%), and thrombocytopenia (14%).

Any-grade nonhematologic TEAEs included upper-respiratory tract infections (18%), pyrexia (12%), rash (16%), peripheral sensory neuropathy (16%), nasopharyngitis (10%), hypertension (12%), cardiac failure (4%), and infusion reaction (32%). No deaths were reported on the study.

We now have doublet, triplet, and quadruplet up-front regimens for patients with newly diagnosed multiple myeloma, Braunstein said. The more agents you combine synergistically to target the plasma cell clones, the deeper response rates you can achieve and that consistently correlates with longer remissions.

Belantamab Mafodotin Triplet for Relapsed/Refractory Multiple Myeloma

Belantamab mafodotin in combination with bortezomib and dexamethasone (B-Vd) demonstratedan acceptable safety profile, according to preliminary findings from a cohort of the phase 1/2 DREAMM-6 trial also presented during the meeting.3

In the 2-part, open-label, phase 1/2 study, investigators evaluated the safety and efficacy of the addition of belantamab mafodotin to B-Vd, 2 standard-of-care doublet regimens, in patients with relapsed/refractory multiple myeloma who have previously received at least 1 line of therapy. To be eligible for the trial, patients had to have measurable disease, acceptable organ function, and an ECOG performance status of 0 to 2. Those who underwent previous autologous stem cell transplant and those who were not candidates for transplant were permitted, along with those who were refractory to bortezomib.

The primary end points of the trial were safety, tolerability, and ORR as defined by the International Myeloma Working Group Uniform Response Criteria. Key secondary end points included preliminary clinical activity, further safety/tolerability examination, pharmacokinetic assessments, and the health-related QOL impact of the combination.

In arm A, belantamab mafodotin was combined with lenalidomide and dexamethasone (B-Rd) and, in arm B, belantamab mafodotin was combined with B-Vd.Part 1 was a dose-escalation phase and part 2 is an ongoing dose-expansion phase for each of the arms with either single (day 1) or split dosing (day 1 and 8) for belantamab mafodotin at 2.5 mg/kg or 3.4 mg/kg.

Results on 18 patients who received the 2.5-mg/kg dose of B-Vd experienced an ORR of 78% (95% CI, 52.4%-93.6%). In addition, patients demonstrated a clinical benefit rate of 83% (95% CI, 58.6%-96.4%) and the VGPR was 50%. The duration of response with the combination had not yet been reached.

Moreover, 89% of patients experienced grade 3 or 4 AEs. Dose reductions were required in 72% of patients because of AEs and all patients experienced a dose interruption or delay due to keratopathy and/or thrombocytopenia. Notably, all toxicities were found to be clinically manageable.

I believe belantamab mafodotin offers a unique therapeutic approach, which is very much needed in [patients with] refractory multiple myeloma, Braunstein concluded.

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Roche receives FDA clearance for BK virus quantitative test on cobas 6800/8800 Systems to support better care for transplant patients – GlobeNewswire

Wednesday, September 9th, 2020

Basel, 8 September 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced U.S. Food and Drug Administration (FDA) 510k clearance for the cobas BKV Test on the cobas 6800 and 8800 Systems. The test was previously granted FDA Breakthrough Device designation demonstrating the improved treatment or diagnosis of life-threatening diseases or conditions for transplant patients. The test provides standardised, high-quality results that can help healthcare professionals better assess the risk of complications caused by the BK virus in transplant patients and identify effective treatment options.

BK virus (BKV) is a member of the polyomavirus family that can cause severe transplant-associated complications. Infection can occur without symptoms and happen early in life. After primary infection, the virus can remain inactive, only to possibly reactivate in immunocompromised individuals such as transplant recipients.

Our diagnostic tests can help clinicians greatly improve patient treatment plans and make quick adjustments for personalised healthcare, said Thomas Schinecker, CEO Roche Diagnostics. This FDA clearance allows Roche to offer healthcare professionals a transplant testing portfolio that includes Cytomegalovirus, Epstein-Barr virus and BK virus so they can simultaneously monitor and improve care for transplant patients who are at risk for these common infections or viral reactivations which can cause further illness or death.

The cobas BKV Test is a polymerase chain reaction (PCR) viral load test that runs on the fully automated and widely available cobas 6800 and cobas 8800 Systems. Along with the previously approved cobas EBV and CMV Tests, the cobas BKV Test has been calibrated to the World Health Organization (WHO) International Standard. This means that test results are reported in international units, making it possible for laboratories anywhere in the U.S. to obtain comparable results when measuring levels of BKV DNA.

About the cobas BKV TestThe cobas BKV Test was previously granted Breakthrough Device Designation by the FDA, together with the cobas EBV Test.

The cobas BKV Test is a real-time polymerase chain reaction (PCR) test with dual-target technology that provides quantitative accuracy and guards against the risk of sequence variations that may be present in the BK virus. The cobas BKV Test has robust coverage with a limit of detection of 21.5 IU/mL and an expanded linear range from 21.5 IU/mL to 1E+08 IU/mL in EDTA plasma.

The test offers an alternative to lab-developed tests (LDTs) or Analyte Specific Reagent (ASR) combinations, potentially minimising variability and complexity in testing, reducing workload and alleviating risk for laboratories. The test supports the goal of result standardisation across institutions by providing reproducible, high-quality results for clinical decision-making.

The fully automated cobas BKV Test and the cobas CMV and cobas EBV Tests can run on the cobas 6800/8800 Systems simultaneously, providing absolute automation with proven performance and flexibility, leading to time savings and increased efficiency.

About BK polyomavirus BK polyomavirus (BKV) is a member of the polyomavirus family that can cause transplant-associated complications including nephropathy in kidney transplantation and hemorrhagic cystitis in hematopoietic stem cell transplantation. Infection can occur early in life, often with no symptoms. After primary infection, the virus can remain inactive throughout life, only to possibly reactivate in immunocompromised individuals, such as patients who receive solid-organ transplants. For kidney transplant patients, BKV infection is considered the most common viral complication, causing polyomavirus nephropathy (PVN) in up to 10 percent of kidney transplant recipients, and about 50 percent of PVN-affected patients will experience transplant graft failure.1 BKV is also associated with hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.2

About the cobas 6800/8800 SystemsWhen every moment matters, the fully automated cobas 6800/8800 Systems offer the fastest time to results with the highest throughput and the longest walk-away time available among automated molecular platforms. The systems provide up to 96 results in about three hours and 384 results for the cobas 6800 System and 1,056 results for the cobas 8800 System in an eight hour shift.*

Both systems make it possible for labs to perform up to three tests in the same run with no pre-sorting required. The systems also enable up to eight hours (cobas 6800 System) and four hours (cobas 8800 System) of walk-away time with minimal user interaction.*

These real-time PCR systems serve the areas of infectious disease, donor screening, sexual health, transplant, respiratory and antimicrobial stewardship.

Through an ever-increasing worldwide install base of cobas 6800/8800 Systems, labs are quickly and easily processing millions of tests per month to meet the changing demands of their communities, their customers, and the patients relying on the results of each assay. Globally, labs know and trust that a Roche assay guarantees high precision, accuracy, and traceability to World Health Organization standards.

Today, rapid advancements in healthcare technology, a shortage of skilled workers, industry-wide consolidation, and the proven need to be ready for the next outbreak have health systems looking to lay a reliable foundation for the future. With proven performance, absolute automation, and unmatched flexibility delivering unparalleled throughput 24/7cobas 6800/8800 Systems are designed to ensure a labs long-term sustainability and success now, more than ever.

Learn more now: http://www.cobas68008800.com or http://diagnostics.roche.com.*May vary based on workflow demands

About RocheRoche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve peoples lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the worlds largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References[1] Jamboti, J. S. (2016) BK virus nephropathy in renal transplant recipients. Nephrology, 21: 647 654. doi: 10.1111/nep.12728. [2] Hirsch HH, Randhawa PS; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13528. doi:10.1111/ctr.13528

Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com

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ASX Biotechs Surfing The Covid Story – FN Arena News

Sunday, August 16th, 2020

Weekly Reports | Aug 10 2020

By Tim Boreham, Editor, The New Criterion

The ASX biotechs surfing the COVID-19 story

Normally investors shun speculative plays in times of market uncertainties, but thats not been the case with ASX-listed life sciences stocks across the drug, diagnostics and device sectors.

Naturally, the biotechs drawing a connection with fighting or detecting the virus spurious or otherwise have seen their valuations soar. Not that investor interest is limited to the Covid cluster, with capital raisings in the sector supported across the board.

A notable winner valuation-wise is Genetic Signatures ((GSS)), which markets molecular diagnostics tests for bacterial and viral conditions including superbugs, sexually transmitted diseases and norovirus (the number one plague of cruise ships before the coronavirus hopped on board).

Sold under the Easyscreen brand, the kits allow for rapid and accurate detection in large volumes. The tests take the genetic information of the targeted organism and change the genetic sequence to reduce the number of variables.

And, yes, the company is a COVID-19 story as well. Before the plague descended, the companys Easyscreen tests had not been able to distinguish Sars-cov-2 from say, Severe Acute Respiratory Syndrome (SARS), but the company has devised a variant to do just that.

Reporting a 278% revenue surge to $4.7m for the June quarter, management called out demand for the COVID-19 tests as a growth driver.

Broker Bell Potter notes the global molecular diagnostics market was worth more than $US6bn in 2018 and is expected to grow to $US10bn by 2026.

The sectors also been a hotbed of acquisitions, such as Thermo Fishers recently-lobbed $US11.5bn offer for Dutch diagnostic group Qiagen and Danaher Corps $US4bn acquisition of US counterpart Cepheid in 2018.

We expect merger and acquisition activity to continue in the space and Genetic Signatures is strategically well positioned to attract interest as it further expands into key US and European markets and grows is product suite, Bell Potter says.

While Genetic Signatures is a case of building incremental revenues, stem cell developer Mesoblast ((MSB)) is on the cusp of company-moving announcements pertaining to several late-stage clinical trials and expected US approval of its therapy for graft versus host disease (a common affliction for transplant patients).

Naturally, most investors are focused on the COVID-19 trial which involves treating critical-care patients with its off the shelf therapy remestemcel-L (branded Ryoncil).

Most coronavirus victims die from acute respiratory distress syndrome (ARDS), an inflammatory condition caused by the immune systems response to the virus.

Mesoblast aimed to enrol 300 patients across 30 US hospitals a moving target given the disease epicentre is moving from region to region.

Nonetheless, the first patients were dosed in May, with an interim analysis is due when at least 30% of the patients have been treated for 30 days.

In other words, investors should soon know whether the company is on the cusp of a major treatment breakthrough.

And if thats not enough excitement, Mesoblast expects to announce results from two phase III studies: a 566-patient effort for chronic heart failure and a 404-patient trial for chronic lower back pain caused by disc degeneration.

Also in the stem-cell space, Cynata Therapeutics ((CYP)) is planning to carry out its own COVID-19 clinical trials not just in relation to ARDS, but sepsis and cytokine release syndrome (all causes of COVID-19 deaths).

The company is encouraged by pre-clinical modelling and has regulatory approval to carry out a trial.

The company planned to enrol 24 intensive care patients in NSW but perhaps it should refocus efforts south of the Murray.

It was fairly clear that Australias prevention measures effectively flattened the curve and we quickly ran out of available patients, Cynata chief Ross Macdonald said before the Victorian resurgence.

Tackling the cause of COVID-19 mortalities is one thing, but what if the risk of contracting the diseases could be more accurately predicted beyond the clinical factors of age and co-morbidities such as heart disease and diabetes?

That way, the denizens of locked down geographies such as Victoria could discard their masks and emerge from isolation.

Meanwhile, shares in kidney disease house Dimerix ((DXB)) last week soared on positive clinical results pertaining to a rare condition called focal segmental glomerusclerosis (FSGS).

But the drug candidate in question, DMX-200 has also been selected for appraisal in a global trial to treat ARDS, the common element between ARDS and FSGS being fibrosis.

Known in shorthand as REMAP-CAP, the World Health Organisation endorsed trial aims to enrol 7000 patients across more than 200 sites. DMX-200 is one of many potential therapies being looked at, but the beauty for Dimerix is the trial costs are paid the governments that are funding REMAP-CAP.

Changing tack, molecular diagnostics house Genetic Technologies ((GTG)) has filed a provisional patent for a genetics-based assessment of the risk of developing COVID-19.

Based on third-party genomic data from 1500 COVID-19 patients, the company intends to develop a prototype model to identify patients most likely to require hospitalisation should they contract the disease.

If and when a vaccine materialises, the genetic profiling could help to prioritise who gets jabbed first.

Hitherto known for its predictive breast cancer kits, Genetic Technologies has never matched its performance to its promises.

But US investors have been willing to support the stock, with the company raising $US5.1m in a placement via its Nasdaq listing.

Disclaimer: Under no circumstances have there been any inducements or like made by the company mentioned to either IIR or the author. The views here are independent and have no nexus to IIRs core research offering. The views here are not recommendations and should not be considered as general advice in terms of stock recommendations in the ordinary sense.

Content included in this article is not by association the view of FNArena (see our disclaimer).

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ASX Biotechs Surfing The Covid Story - FN Arena News

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Merck and Eisai Receive Complete Response Letter for KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) Combination as First-Line Treatment for…

Friday, July 10th, 2020

Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding Merck’s and Eisai’s applications seeking accelerated approval of KEYTRUDA, Merck’s anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). The applications were based on data from the Phase 1b KEYNOTE-524/Study 116 trial, which showed clinically meaningful efficacy in the single-arm setting. These data were recently presented at the 2020 American Society of Clinical Oncology Annual Meeting and supported a Breakthrough Therapy designation granted by the FDA in July 2019. Ahead of the Prescription Drug User Fee Act (PDUFA) action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that KEYTRUDA in combination with LENVIMA represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination. As such, LEAP-002, the Phase 3 trial evaluating the KEYTRUDA plus LENVIMA combination as a first-line treatment for advanced HCC, is currently underway and fully enrolled. The CRL does not impact the current approved indications for KEYTRUDA or for LENVIMA.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200708005239/en/

Merck and Eisai are continuing to evaluate the KEYTRUDA plus LENVIMA combination across 13 different tumor types in 18 clinical trials, including the LEAP (LEnvatinib And Pembrolizumab) clinical program.

About KEYTRUDA® (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA® (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Endometrial Carcinoma

KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those 2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those 2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those 2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (20%) were fatigue (29%), diarrhea (24%), and rash (24%).

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Merck and Eisai Receive Complete Response Letter for KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) Combination as First-Line Treatment for...

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FDA Approves Talaris Therapeutics’ IND for Its Allogeneic Cell Therapy FCR001 to Be Evaluated in Patients With a Severe Form of Scleroderma – Business…

Friday, July 10th, 2020

BOSTON & LOUISVILLE, Ky.--(BUSINESS WIRE)--Talaris Therapeutics, Inc., a privately held biotechnology company developing transformative cell therapies that have the potential to induce durable immune tolerance across a range of indications, announced that the U.S. Food and Drug Administration (FDA) has approved the companys Investigational New Drug (IND) application for the evaluation of Talaris novel cell therapy FCR001 in the treatment of diffuse systemic sclerosis (SSc), a severe form of the rare autoimmune disease scleroderma. Approval of this IND allows Talaris to initiate a Phase 1/2a trial at sites across the U.S., including Duke University and the University of Michigan.

Were very eager to study the tolerogenic potential of FCR001 for patients with severe autoimmune disease, said Scott Requadt, Chief Executive Officer of Talaris. Individuals with diffuse cutaneous systemic sclerosis, a subset of scleroderma with high morbidity and mortality, are in great need of safe and effective, disease-modifying, treatment options. We believe FCR001 could represent an important new approach to treating this serious condition.

Scleroderma, which derives from the Greek words sclero, meaning hard, and derma, meaning skin, is a rare and potentially fatal chronic autoimmune disease which causes progressive scarring, or fibrosis, of the bodys connective tissues. Scleroderma can either be localized or systemic. Systemic scleroderma, also called systemic sclerosis (SSc), is further divided into the limited cutaneous subset and the diffuse cutaneous subset, depending on the degree of skin involvement. Both types affect the skin and vital internal organs, especially the lungs, kidneys, gut and heart, resulting in organ dysfunction. Patients with the diffuse subset generally have rapidly progressive skin and internal organ involvement and have worse outcomes than the limited subtype.

Based on encouraging data from randomized clinical trials, autologous hematopoietic stem cell transplant (HSCT) is increasingly used to treat severe cases of diffuse cutaneous SSc, where it has been shown to halt organ damage and induce clinical remission. However, because patients are transplanted with their own stem cells, there is a risk of disease recurrence, and patients typically must first undergo full myeloablative conditioning with or without total body irradiation, which is associated with direct organ toxicity and increased risk of future cancers.

Talaris allogeneic cell therapy, FCR001, is a novel, one-time treatment intended to induce immune tolerance in the recipient and which can be used across all levels of donor-recipient HLA mismatch. Treatment with FCR001 is preceded by non-myeloablative conditioning. In a Phase 2 clinical trial in de novo living donor kidney transplant recipients, FCR001 resulted in durable immune tolerance in 70% of the 37 recipients treated; these individuals were able to successfully discontinue their anti-rejection medications and no tolerized patient has had to resume immunosuppression (median follow-up of over 5 years, longest follow-up is over 10 years). Furthermore, seven of the successfully tolerized patients had kidney failure due to an underlying autoimmune disease, and none of these patients has experienced recurrence of their underlying autoimmune disease post-treatment. Based on these encouraging data and its broad therapeutic potential in autoimmune disease, FCR001 will be evaluated in a planned Phase 1/2a trial of patients with diffuse cutaneous SSc.

A safe, allogeneic stem cell transplant treatment using nonmyeloablative conditioning could offer important additional benefits over current autologous HSCT as a treatment for this severe form of systemic sclerosis, said Keith Michael Sullivan, M.D., Professor of Medicine at Duke University Medical School.

The diffuse cutaneous systemic sclerosis subset I see in my practice have very limited treatment options. Autologous stem cell transplant has demonstrated the potential to induce durable remissions in randomized clinical trials, but involves significant risks to the patients, said Dinesh Khanna, M.D., M.Sc., Director of the Scleroderma Program and Professor of Medicine at the University of Michigan Medical School. I am excited to participate in this clinical trial of FCR001, and hopeful that it could result in a safer and more durably effective treatment for these patients.

About FCR001

FCR001 is an investigational, allogeneic cell therapy developed by Talaris Therapeutics to induce or restore patients immune tolerance. FCR001 builds on over 30 years of research by the companys founder, Dr. Suzanne Ildstad, into the means by which durable immune tolerance can be induced in a patient who receives a transplanted organ or can be restored in patients with certain immune-mediated or blood disorders. FCR001 has received both Orphan Drug Designation and Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration. A Phase 3 trial of FCR001 in living donor kidney transplant recipients, FREEDOM-1, is now enrolling patients; more information can be found at: http://freedom1study.com/

About Talaris Therapeutics

Talaris Therapeutics, Inc. is a late-clinical stage biotechnology company that is developing transformative cell therapies with the potential to eliminate the burden of chronic immunosuppression for organ transplant recipients as well as induce durable remissions in patients with severe auto-immune and immune-mediated disorders. Talaris was founded on technology discovered and developed by Dr. Suzanne Ildstad and operates its own cell processing facility in Louisville, KY. Talaris is backed by leading life sciences investors Blackstone Life Sciences, Longitude Capital and Qiming Venture Partners USA and maintains corporate offices in Boston, MA and Louisville, KY. http://www.TalarisTx.com.

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FDA Approves Talaris Therapeutics' IND for Its Allogeneic Cell Therapy FCR001 to Be Evaluated in Patients With a Severe Form of Scleroderma - Business...

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Coronavirus PPP Loans In Livingston: Where The Money Went – Livingston, NJ Patch

Thursday, July 9th, 2020

LIVINGSTON, NJ Federal officials have released a list of businesses across the nation, including in Livingston, which were approved for loans under the Paycheck Protection Program (PPP).

More than 4.9 million loans worth roughly $521 billion have been approved for businesses and nonprofit organizations across the United States under the program, which was established by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act).

See a list of awardees in Livingston below.

The aid is meant to help small businesses keep workers on their payrolls during the COVID-19 crisis. Funds can also be used to pay interest on mortgages, rent, and utilities. PPP loans have an interest rate of one percent and can be fully forgiven under certain conditions. (Learn more about the program)

Roughly 22,000 entities in New Jersey were approved for loans greater than $150,000. Awards in the Garden State also included loans to higher education institutions, private schools, manufacturers, car washes, real estate agent companies and nonprofits.

Earlier this week, the U.S. Small Business Administration (SBA) and U.S. Treasury released a list of loan recipients by town, adding a big caveat about the data:

Several companies that made the list have since questioned its accuracy, claiming that they didn't apply for or receive the funds the government says they did, CNBC reported.

See a list of approved loans over $150,000 in Livingston via the searchable database below. Enter the town's name where it says "Search business name of town" to begin.

More here:
Coronavirus PPP Loans In Livingston: Where The Money Went - Livingston, NJ Patch

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Stem Cell Therapy For Kidney Failure. Learn More Now …

Tuesday, July 7th, 2020

Kidney failure (or renal failure) is a condition in which the kidneys fail to function properly. Physiologically, renal failure is described as a decrease in blood filtration (glomerular filtration rate or GFR). Clinically, this is manifested in elevated serum creatinine. Still not well understood are many of the factors that are involved in kidney failure. Researchers are studying the effects of nutritional proteins and the concentration of cholesterol in the blood.

Acute renal failure: Some kidney problems happen quickly, such as from an accident that causes kidney damage. A great loss of blood can cause sudden kidney failure, also some drugs or poisons can cause the kidneys to stop working. Such sudden drops in kidney function are called acute renal failure.Are you living with Kidney Failure? Call us today for a FREE consultation for stem cell therapy or fill out the Case Evaluation Form to begin.ProgenCells stem cell procedures are scientifically designed and professionally followed; we have one goal in mind: substantial health improvement of people with simple logistics.

We do not suggest that patients substitute their current medical doctor or abandon current treatments. Since this is a long-term protocol, is necessary that your current medical doctor continues to follow up on your case.

Information: Our medical experts study your case, your current condition as well as your health history. After a full evaluation it is decided if you could be eligible to participate in this protocol, and receive cell therapy. A multidisciplinary medical committee studies your case and honestly considers your improvement potential.

After your case is evaluated, a ProgenCell staff member will contact you regarding your particular case and potential benefits. We also answer any question you may have about the procedure or the requirements to make it happen.

Plan: Once you have consented, we can plan ahead. Because of ProgenCells high demand, it is necessary to schedule a date for your procedure at least 2 to 3 weeks in advance. Exceptions can be made when the condition of the patient requires urgent care.

Conditioning and medical procedure: When your appointment is scheduled, we will assign you an agent that will become your personal assistant related to your medical procedure. This assistant will be able to help you with administrative tasks, logistics, planning your stay, communication with the medical staff, etc. Your personal agent will provide you the proper documentation to complete your medical records and will explain the informed consent. In short, we will coordinate all thats necessary for a practical and easy stay with ProgenCell. The complete treatment from beginning to end- will take from 3 to 6 hours, depending on the case. During your recovery time you will have access to a telephone, TV and internet.Call us today for a FREE consultation or fill out the Case Evaluation Form to begin cell therapy.

Acute renal failure (ARF) is, as its name implies, a rapidly progressive loss of renal function, generally characterized by oliguria, a decreased urine production (measured as less than 400 mL per day for adults, less than 0.5 mL/kg/hour in children, or less than 1 mL/kg/hour in infants), and water imbalance of body fluids and electrolyte disorders.

Chronic renal failure (CRF) is the condition that is caused by permanent and irreversible damage to kidney function, secondary to any cause. Worldwide, the most common causes (but not the only) of chronic kidney disease include diabetes, hypertension, and obstructive diseases of the urinary tract (such as stones, tumors, etc.). It can arise from the complication of a large number of kidney diseases such as IgA nephropathy (Berger disease), inflammatory diseases of the kidney (collectively called glomerulonephritis), chronic pyelonephritis and urinary retention, and the use of toxic drugs to the kidney (particularly contrast media and some antibiotics). Terminal renal failure is the ultimate result, which usually requires dialysis until a donor can be found for a kidney transplant.

If the disease is detected early, the speed with which the damage progresses can be slowed, delaying the onset of replacement therapies and giving the patient more time to prepare for such therapy. Currently available renal replacement therapies are hemodialysis, peritoneal dialysis, and renal transplantation.

Causes of Kidney FailureIn the United States, about 80,000 people are diagnosed with kidney failure each year. This is a serious condition. Diabetes is the most common cause of kidney failure and constitutes more than forty percent of new cases. Even when drugs and diet can control diabetes, the disease can lead to nephropathy and kidney failure. There are about sixteen million diabetics in the United States and of those, about 100,000 suffer from kidney failure due to diabetes.People with kidney failure must undergo dialysis in either of two modes or transplantation to receive a kidney from a healthy donor. Blacks, American Indians, and the descendants of Hispanic Americans have diabetes, kidney disease, and renal failure in a proportion higher than the general population. Scientists have been unable to explain this phenomenon and cannot explain fully the interplay of factors leading to diabetic nephropathy. These factors include heredity, diet, and other conditions such as hypertension.

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Stem Cell Therapy For Kidney Failure. Learn More Now ...

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Anemia in chronic kidney disease – kidneyfund.org

Tuesday, July 7th, 2020

Are you at risk for anemia?

Take our short quiz to learn more about the symptoms of anemia.

There's more to chronic kidney disease than you think...

If your kidneys are not working properly, they may not be able to help your body make the red blood cells it needs. Anemia is a common side effect of kidney disease.

Anemia happens when there are not enough red blood cells in your body.

Red blood cells carry oxygen through your bloodstream, giving you energy and helping your muscles, bones, and organs work properly.

The oxygen that we breathe in passes through our lungs and into the red blood cells.

In anemia, there are not enough red blood cells to carry this oxygen around the body.

Anemia can make you feel weak and tired because you are not getting the energy you need.

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Anybody can develop anemia, but it is very common in people with CKD. People with CKD may start to have anemia in the early stages of CKD, and anemia usually gets worse as CKD gets worse. If your kidneys are not working as well as they should, you are more likely to get anemia.

Anemia in CKD is more common if you:

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Anemia can happen with or without symptoms. Many of the symptoms of anemia can also be caused by other problems. The only way be sure if you have anemia is to get tested. If you are experiencing symptoms, it is important that you talk to your doctor.

Feeling dizzy or having difficulty concentrating may be a sign that your brain is not getting enough oxygen.

Paleness is caused by reduced blood flow or a lower number of red blood cells.

Anemia in CKD can increase your risk of heart problems because the heart has to work harder to provide blood to your body. If you experience an unusually fast heart rate or are worried about your heart health, please speak to your doctor.

Your blood may not have enough red blood cells to deliver oxygen to your muscles. By increasing your breathing rate, your body is trying to bring more oxygen into your body.

Easy fatigue, loss of energy, and reduced physical capacity

Sensitivity to the cold may mean there is not enough oxygen being delivered in the blood to your body

Take our short quiz to learn more about the symptoms of anemia.

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There are two main causes of anemia in CKD:

All of the cells in your body live for a certain amount of time and then die. Your body is always working to make new cells to replace the ones that have died. Red blood cells live for about 115 days. Your kidneys help your body make red blood cells.

Healthy kidneys make a hormone called erythropoietin (EPO). EPO sends a signal to the body to make more red blood cells. If your kidneys are not working as well as they should, they cant make enough EPO. Without enough EPO, your body doesnt know to make enough red blood cells. This means fewer red blood cells are available for carrying oxygen through your body.

Iron is a mineral found in many foods, such as meats and leafy greens. Your body uses iron to make red blood cells. A common cause of anemia in people with CKD is iron deficiency. Iron deficiency means you do not have enough iron in your body. It can be caused by not getting enough iron in your diet or by losing blood, either through blood tests or during dialysis. If you dont take in enough iron through your diet, you can get anemia. Around half of people with CKD stages 2 to 5 have some kind of iron deficiency.

There are several kinds of anemia. Anemia caused by having too little EPO or too little iron in your body are the most common in people with CKD. Talk to your doctor to learn more.

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Talk to your doctor if you think you may have anemia. The only way to know if you have anemia is to have a blood test. When you have kidney disease, your doctor will want you to have blood tests often. These tests are used to check not only your kidney function, but also for signs of any other problems, such as the number of red blood cells and how much iron you have in your body.

The test for anemia is a simple blood test to check for the amount of hemoglobin in your blood. Hemoglobin is a part of your red blood cells. Figuring out the amount of hemoglobin you have in your blood can tell your doctor how many red blood cells you have.

Your doctor may also ask you if youve noticed any symptoms, such as changes in skin color or feeling unusually tired.

Take our short quiz to learn more about the symptoms of anemia.

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Getting your anemia treated can help you feel better. Depending on the cause of your anemia, your doctor may recommend one of the following treatments:

Doctors and researchers are working on potential new treatments for anemia. New treatments in development are tested in clinical trials. If youre interested in joining a clinical trial to try an investigational new treatment for anemia, visit ClinicalTrials.gov to learn about all available clinical trials for anemia.

If you have CKD, getting early treatment for your anemia can help slow the progress of your CKD. If you think you might have anemia, talk to your doctor about getting tested.

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Anemia and end-stage renal disease (ESRD), also known as kidney failure, often go hand in hand. Most people with kidney failure who are on dialysis have anemia. Kidney transplant patients are also at higher risk for anemia. Learn more.

Click here to download a copy of the Anemia in ESRD booklet.

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Talk with your doctor or another member of your health care team to find out more about your anemia symptoms and treatment options. Our Talk to Your Doctor Guide can help you get the conversation started.

Note: This survey is not a medical diagnosis. This guide is an awareness tool designed for you and your doctor to use together. The information you provide is anonymous and will not shared.

Get started

Question 1 of 7

How often do you feel tired and/or weak and dont know why?

Not often

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How much does that bother you?

Not at all

A little

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Question 2 of 7

How often do you notice your heart beating faster than normal?

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How much does that bother you?

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Question 3 of 7

How often do you have trouble breathing or catching your breath?

Not often

Sometimes

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How much does that bother you?

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Question 4 of 7

How often do you feel dizzy?

Not often

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Often

How much does that bother you?

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Question 5 of 7

How often do you have trouble concentrating?

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How much does that bother you?

Not at all

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Question 6 of 7

How often do you feel cold when others do not?

Not often

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How much does that bother you?

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Question 7 of 7

Does your skin look unusually pale or dull?

See the article here:
Anemia in chronic kidney disease - kidneyfund.org

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Dr Borehams Crucible: Mesoblast within months of 3 major trial results, key regulatory decision – Stockhead

Tuesday, July 7th, 2020

The worlds biggest listed pure-play stem cell developer has a busy slate of clinical work, notably in therapies for advanced heart failure, chronic back pain and graft-versus-host disease (GvHD).

Now these programs are approaching a thrilling denouement and, as the Demtel man enthused, theres more: Mesoblast (ASX:MSB) is also undertaking an expanded coronavirus trial after a 12-patient effort showed promising results in treating acute respiratory distress syndrome (Ards), the usual cause of death with COVID-19.

The patients received infusions of Mesoblasts allogeneic (off the shelf) mesenchymal stem cell candidate, remestemcel-L, acquired from Osiris for $106m in 2013.

Meanwhile, results from two phase III trials are expected this (September) quarter: a 566-patient effort for chronic heart failure and a 404-patient trial for chronic lower back pain caused by disc degeneration.

And in September, the US Food and Drug Administration will rule on whether or not the company can market its GvHD therapy on American shores.

Mesoblast founder and CEO Prof Silviu Itescu notes that across all its therapies the company is targeting the most severe cases where alternative therapies dont exist.

Mesoblasts proprietary process selects precursor and stem cells from the bone marrow of healthy adults, creating a master cell bank. This cell kitty is then expanded into thousands of doses for off-the-shelf use, without the need for tissue matching.

Mesoblast is targeting a common market across all its disease indications: inflammation. In the case of heart disease, tissue macrophages (cells) churn out inflammatory factors that damage heart muscle and cause fibrosis and vascular dysfunction.

The stem cells respond to severe inflammation by switching the culprit macrophages off and converting them to nice cells that actually protect the heart muscle.

This is the central mechanism in each of our disease states: heart failure, back pain, GvHD and rheumatoid arthritis, Professor Itescu says. We have the potential to make a big difference in some very big disease states where inflammation is central.

Backed by the Pratt familys listed investment vehicle Thorney Investments, Mesoblast debuted on the ASX in 2004 and reached a peak valuation of $2.5bn in 2011 before suffering a reality check.

Culprits included a phase II heart trial that failed to meet primary endpoints, a badly executed Nasdaq listing and Israel pharma house Teva Pharmaceuticals decision to walk away from a heart program partnership in 2016.

Mesoblast dual listed on the Nasdaq in November 2015, accompanied by a $US63m capital raising.

The companys Ards and GvHD programs are based on mesenchymal stem cell assets acquired from US pharma group Osiris Therapeutics in October 2013.

Mesoblasts own-developed cells are called mesenchymal precursor cells and they are being developed for rheumatoid arthritis and diabetic nephropathy, as well as the aforementioned heart failure and lower back pain programs.

Ards is bought on by an excessive immune response to the virus in the lungs. The immune cells produce inflammatory cytokines, which destroy lung tissue and can also damage the liver, kidney and heart.

Remestemcell-L has the potential to tame the cytokine storm in Ards and may offer a life-saving treatment for those unfortunate individual sufferers of COVID-19 Ards, Professor Itescu says.

Mesoblasts COVID-19 proclamations have been coming so thick and fast that its been Ard(s) just to keep up. But the core excitement cluster was around Mesoblasts April 23 disclosure of the results of the trial at New Yorks Mt Sinai Hospital, covering moderate to acute Ards cases.

Under the compassionate use protocol, the patients were treated with two infusions of remestemcel-L over the first five days.

The results? Nine of the 12 patients came off a ventilator within a median 10 days, with 83 per cent survival (the Grim Reapers spin on this is that two of them died).

In comparison, only 9 per cent of patients at one reference hospital (38 out of 445 patients) were able to come off the ventilator with standard-of-care treatment.

Another US hospital reported that only 38 patients of 320 or 12 per cent survived.

Of course, 12 people good and true are adequate numbers for a jury, but sub-optimal to comprise a statistically significant trial.

Thus, the company is enrolling 300 patients in a phase III, randomised, controlled trial of severe Ards patients at 30 sites.

The first patients were dosed in early May, with about 15 sites established as the company chases the disease from the northeast to the southern states.

Mesoblast chief medical officer Professor Fred Grossman says the company is carefully choosing hot spots such as Alabama which, as of late May had the no vacancy signs outside its intensive care wards.

The sites are recruiting quite quickly, he says. There is a tremendous interest in this study.

The trial leaders will undertake an interim analysis at 30 days, and when 30 per cent of patients have reached their primary endpoint. At that point the trial can be dumped on futility grounds, or expanded to the control group because it appears to be working.

Remestemcell-L has investigational new drug (IND) status with the US Food and Drug Administration, meaning the company swiftly can initiate trials on patients with very dismal prospects.

Long-suffering Mesoblast investors will recall that the companys shares tumbled 28 per cent in November 2018 after a 159-patient trial of Rexlemestrocel-L (Revascor) for end-stage heart failure did not meet its primary endpoint of weaning patients from left ventricle assist devices (LVADs or heart pumps).

The company claimed the endpoint was set by the independent !!! investigators and was of little real clinical interest. What really mattered was that the trial showed reduced gastrointestinal bleeding by 76 per cent and hospitalisations by 65 per cent.

Investors are now nervously awaiting the first readout of the broader 566-patient chronic heart failure trial across 59 US sites.

Mesoblast targeted patients with class three or four disease, the sickest 15 to 20 per cent of patients who have failed standard-of-care drugs.

Class three patients have a 20 per cent chance of dying within two years while with class four its a case of flip a coin that you will be around in 12 months.

At this stage, Mesoblast retains its heart treatment rights except in China, where it is partnered with Tasly Pharmaceutical.

Mesoblasts phase III back pain trial aimed to enroll 404 patients with lower back pain caused by degenerative disc disease.

The endpoint of the trial, dubbed MPC-06-ID, is an improvement in pain and function over 24 months.

As with the heart trial, results are imminent and its a toss-up as to what release will hit the ASX announcements feed first.

The company is liaising with its global back pain partner Grunenthal GmbH about the clinical protocol for a European phase III confirmatory trial.

In Japan, Mesoblast is partnered with JCR Pharmaceutical for its approved GvHD treatment called Temcell and its off and racing in that smallish but enthusiastic market.

Meanwhile, the company is angling to enter the US market for a similar GvHD treatment, branded Ryoncil.

GvHD afflicts about half of the 30,000 patients annually undergoing allogeneic bone marrow transplant, typically for blood cancers, with their bodies rejecting the alien transplant.

In March, the FDA granted priority review with a September 30 action date, but we might have a good idea of the outcome in August.

Why? Because thats when the FDAs relevant advisory committee meets to vote on the matter and the (virtual) gathering is open to the public.

A date is yet to be set. While advisory committee views are not binding on the FDA, they usually presage the final decision.

If approved, Mesoblast could be selling Ryoncil in the US by the time were carving the Christmas turkey (badly, in the case of your columnist).

Buoyed by the COVID-19 results, Mesoblast in May wasted no time tapping institutional investors for an idle $US90m ($129.6m) in a placement.

Mesoblast already had a healthy cash balance of $US60m.

The raising was struck at $3.20 a share, a modest 7 per cent discount to the prevailing price.

The funds, in the main, will be used to scale-up manufacturing of remestemcell-L and to support the phase III trial, as well as for working capital and general corporate purposes.

The company also has $US67m available through existing financing facilities and partnerships.

Mesoblast reported revenue of $US31.45m for the nine months to March 2020, up 113 per cent. The reported loss narrowed 34 per cent to $US45.3m, reflecting curtailed research and development spend by $US7.5m, or 15 per cent.

The revenue included $US5.9m of JCR royalties from Temcell sales in Japan and milestone revenue of $US25m.

The company stands to pocket up to $US150m of royalties and milestones from Grunenthal prior to any European launch of Revascor.

Successful sales could result in up to $US1bn in milestone payments.

Over the last decade, Mesoblasts ASX shares have traded as high as $9 (October 2011) and as low as $1.03 (December last year).

To the Meso-sceptics the company has promised far too much with limited commercial success, while raising $1bn since listing 16 years ago.

Dare we say that Mesoblast now looks more focused and to be getting somewhere?

When we last covered Mesoblast in March 2019, Professor Itescu said he was 95 per cent certain the company would do what no other Aussie biotech in phase III had done: win FDA drug approval.

Well, Clinuvel has stolen that Aussie first honour, but Mesoblast is well placed to get over the line with a GvHD treatment in the US, which presents a market eight times the size of Japans.

Its certainly rare for a biotech to expect results for three major trials and a key regulatory decision in the space of months.

If the heart and back pain results are definitively positive and the FDA green lights GvHD, the company hits the jackpot. If two or more of them bomb lets not go there.

Your ultra conservative columnist regards the COVID-19 stuff as the icing on the cake with an outside chance of success, especially given the hundreds of other programs in the coronavirus-busting sector.

Disclosure: Dr Boreham is not a qualified medical practitioner and does not possess a doctorate of any sort. But he hopes to become proficient in turkey carving by December 25.

This column first appeared in Biotech Daily.

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Dr Borehams Crucible: Mesoblast within months of 3 major trial results, key regulatory decision - Stockhead

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FDA Approves Merck’s KEYTRUDA (pembrolizumab) for First-Line Treatment of Patients With Unresectable or Metastatic MSI-H or dMMR Colorectal Cancer -…

Tuesday, June 30th, 2020

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Mercks anti-PD-1 therapy, as monotherapy for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. The approval is based on results from the Phase 3 KEYNOTE-177 trial, in which KEYTRUDA significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0004]) compared with chemotherapy, the current standard of care. In the study, treatment with KEYTRUDA also more than doubled median progression-free survival (PFS) compared with chemotherapy (16.5 months [95% CI, 5.4-32.4] versus 8.2 months [95% CI, 6.1-10.2]).

Todays approval has the potential to change the treatment paradigm for the first-line treatment of patients with MSI-H colorectal cancer, based on the important findings from KEYNOTE-177 that showed KEYTRUDA monotherapy demonstrated superior progression-free survival compared to standard of care chemotherapy, said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. Our commitment to pursuing biomarker research continues to help us bring new treatments to patients, particularly for those who have few available options.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see Selected Important Safety Information below.

This approval was granted less than one month following the submission of a new supplemental Biologics License Application (sBLA), which was reviewed under the FDAs Real-Time Oncology Review (RTOR) pilot program. This review also was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among its international partners. For this application, a modified Project Orbis was undertaken, and the FDA is collaborating with the Australian Therapeutic Goods Administration, Health Canada and Swissmedic on their ongoing review of the application.

Patients with unresectable or metastatic MSI-H colorectal cancer have historically faced poor outcomes, and until today, chemotherapy-containing regimens were the only FDA-approved first-line treatment options, said Luis A. Diaz, M.D., head of the division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center. In patients who were treated with KEYTRUDA and responded (n=67) in the KEYNOTE-177 trial, 43% of patients experienced a duration of response lasting two years or longer. This approval helps address the unmet need to provide a new monotherapy treatment option for patients.

Data Supporting the Approval

The approval was based on data from KEYNOTE-177 (NCT02563002), a multi-center, randomized, open-label, active-controlled trial that enrolled 307 patients with previously untreated unresectable or metastatic MSI-H or dMMR colorectal cancer. Microsatellite instability (MSI) or mismatch repair (MMR) tumor status was determined locally using polymerase chain reaction or immunohistochemistry, respectively. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible.

Patients were randomized 1:1 to receive KEYTRUDA 200 mg intravenously every three weeks or investigators choice of the following chemotherapy regimens given intravenously every two weeks:

Treatment with KEYTRUDA or chemotherapy continued until Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression of disease as determined by the investigator or unacceptable toxicity. Patients treated with KEYTRUDA without disease progression could be treated for up to 24 months. Assessment of tumor status was performed every nine weeks. Patients randomized to chemotherapy were offered KEYTRUDA at the time of disease progression. The main efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ, and overall survival (OS). Additional efficacy outcome measures were objective response rate (ORR) and duration of response (DOR).

Patients were enrolled and randomized to KEYTRUDA (n=153) or chemotherapy (n=154). The baseline characteristics of these 307 patients were: median age of 63 years (range, 24 to 93), 47% age 65 or older; 50% male; 75% White and 16% Asian; 52% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, and 48% had an ECOG PS of 1; and 27% received prior adjuvant or neoadjuvant chemotherapy. Among the 154 patients randomized to receive chemotherapy, 143 received chemotherapy per the protocol. Of these 143 patients, 56% received mFOLFOX6, 44% received FOLFIRI, 70% received bevacizumab plus mFOLFOX6 or FOLFIRI, and 11% received cetuximab plus mFOLFOX6 or FOLFIRI. The median follow-up time was 27.6 months (range, 0.2 to 48.3 months).

In this study, KEYTRUDA monotherapy significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0004]) and showed a median PFS of 16.5 months (95% CI, 5.4-32.4) compared with 8.2 months (95% CI, 6.1-10.2) for patients treated with chemotherapy. For PFS, in the KEYTRUDA arm, there were 82 patients (54%) with an event versus 113 patients (73%) in the chemotherapy arm. At the time of the PFS analysis, the OS data were not mature (66% of the required number of events for the OS final analysis). For patients treated with KEYTRUDA, the ORR was 44% (95% CI, 35.8-52.0), with a complete response rate of 11% and a partial response rate of 33%, and for patients treated with chemotherapy, the ORR was 33% (95% CI, 25.8-41.1), with a complete response rate of 4% and a partial response rate of 29%. Median DOR was not reached (range, 2.3+ to 41.4+) with KEYTRUDA versus 10.6 months (range, 2.8 to 37.5+) with chemotherapy. Based on 67 patients with a response in the KEYTRUDA arm and 51 patients with a response in the chemotherapy arm, 75% in the KEYTRUDA arm had a duration of response greater than or equal to 12 months versus 37% in the chemotherapy arm, and 43% in the KEYTRUDA arm had a duration of response greater than or equal to 24 months versus 18% in the chemotherapy arm.

Among the 153 patients with MSI-H or dMMR colorectal cancer treated with KEYTRUDA, the median duration of exposure to KEYTRUDA was 11.1 months (range, 1 day to 30.6 months). Adverse reactions occurring in patients with MSI-H or dMMR colorectal cancer were similar to those occurring in 2,799 patients with melanoma or non-small cell lung cancer treated with KEYTRUDA as a single agent.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High (TMB-H)

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

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FDA Approves Merck's KEYTRUDA (pembrolizumab) for First-Line Treatment of Patients With Unresectable or Metastatic MSI-H or dMMR Colorectal Cancer -...

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R3 International Offering Stem Cell Therapy Program for Anti Aging in Mexico – PR Web

Tuesday, June 30th, 2020

Anti Aging Stem Cell Therapy in Mexico (888) 988-0515

SAN DIEGO (PRWEB) June 24, 2020

R3 Stem Cell International announced a new program offering stem cell therapy for anti aging in Mexico. The program offers several options with stem cell counts up to 200 million and pricing starting at $2950.

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R3 International Offering Stem Cell Therapy Program for Anti Aging in Mexico - PR Web

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