StemCell Therapy

Ipsen Cattle Company, Dingle, Idaho, recently re-enrolled in the American Angus Association whole-herd reporting system MaternalPlus as a commitment to making genetic improvements in lifetime cow herd productivity. Breeders participating in MaternalPlus are keenly focused to better evaluate herd reproductive performance, the number one profit driver in the cow-calf industry.

MaternalPlus is a voluntary, inventory-based reporting system that collects additional reproductive trait data to provide Angus breeders and their customers the information they need to make effective selection decisions. To date, more than 140 breeders have completed MaternalPlus enrollment.

The program allows producers to capture cow herd and reproductive performance data, gain faster access to preweaning EPDs as a selection tool, characterize females through heifer pregnancy EPDs tied directly to herd genetics, expand new trait development for Angus reproductive and longevity measures, and streamline their ability to track heifer and cow reproductive records through AAA Login.

In addition, MaternalPlus lays the groundwork for selection tools related to cow longevity in the herd. Gathering these records will allow the Association to cultivate research related to cow herd productivity and make improvements similar to what the Angus breed has witnessed in other economically relevant traits.

For more information on MaternalPlus, visit the Association website or access AAA Login.Ipsen Cattle Company, Dingle, Idaho, recently re-enrolled in the American Angus Association whole-herd reporting system MaternalPlus as a commitment to making genetic improvements in lifetime cow herd productivity. Breeders participating in MaternalPlus are keenly focused to better evaluate herd reproductive performance, the number one profit driver in the cow-calf industry.

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MaternalPlus is a voluntary, inventory-based reporting system that collects reproductive trait data to provide Angus breeders and their customers the information they need to make effective selection decisions. To date, more than 140 breeders have completed MaternalPlus enrollment.

The program allows producers to capture cow herd and reproductive performance data, gain faster access to preweaning EPDs as a selection tool, characterize females through heifer pregnancy EPDs tied directly to herd genetics, expand new trait development for Angus reproductive and longevity measures.

In addition, MaternalPlus lays the groundwork for selection tools related to cow longevity in the herd. Gathering these records will allow the Association to cultivate research related to cow herd productivity and make improvements similar to what the Angus breed has witnessed in other economically relevant traits.

For more information on MaternalPlus, visit the Association website or access AAA Login.

Link:
Local Angus Breeder Recognized for Sustained Efforts to Improve Cow Productivity - The Herald Journal

When it comes to ensuring that the body stays healthy, the liver is definitely at the forefront. Often referred to as the bodys personal detoxing system, the liver helps to keep your body healthy and clean by removing toxins from the body. If thats not enough, this vital organ is also responsible for destroying old blood cells, ensuring that nutrients are more easily absorbed, storing minerals, iron, and vitamin A, as well as producing essential proteins and cholesterol and produce bile to break down and digest fats. That said, its no wonder that people are concerned with maintaining the health of the liver, and as such if theres one trend that will never die, its a liver detox.

Before we get into the effectiveness of a liver detox, its best to first discuss what would bring someone to it. As mentioned, the liver is the bodys personal detox system, and if its compromised, then youre definitely going to feel the effects. That said, below are signs that your liver may need a little help;

Now while the average person may associate poor liver function with excessive alcohol consumption which is fair there are other facts that can compromise your bodys liver function. These include;

A liver detox, or cleanse, often takes the shape of fasting on cayenne-infused lemon water for a week, in hopes of cleaning your liver and even losing weight. Now, while this health fad is often featured on every health website known to men, there are a few concerns when it comes to liver detoxes and cleanses.

For one, these cleanses can be dangerous as they often encourage people to go on diets and fasts that may deprive them of essential nutrients, leading to deficiencies and malnutrition. Whats more, there have yet to be any scientific studies that support the benefits of liver detoxes. Whats more, the products that claim to help to detox the liver are not regulated. Essentially, there is a low chance of an unhealthy liver getting better because of a liver cleanse.

Liver detox may not necessarily be the best way to protect liver health. However, there are other ways that can help to protect it particularly through dietary measures. That said, below is a list of liver-friendly foods that you can add to your diet, boosting your bodys personal detoxing system.

Rich in antioxidants, green tea can do wonders for your health, and that includes your liver as well.

For instance, a Japanese study published in the British Medical Journal found a strong association between drinking 510 cups ofgreen teaper day and improved blood markers of liver health.

Additionally, separate research published in the International Journal of Molecular Medicine found that after drinking green tea for 12 weeks, patients with non-alcoholic fatty liver disease (NAFLD) noted an improvement in their liver enzyme levels. Researchers also noted that green tea may have helped to reduce oxidative stress and fat deposits in the liver.

Lastly, findings published in the Nutrition and Cancer journal revealed that drinking four or more cups a day of green tea can help to reduce your risk of developing liver cancer.

With that said, if youre looking to boost your liver health, its preferable to stick to buying green tea as opposed to green tea extracts. This is because some supplements have been found to damage the liver, as opposed to helping it.

A food group that consists of broccoli, cauliflower, brussels sprouts, and cabbage. These vegetables can help to boost liver health because they are rich in the compound glutathione.

While human studies are limited, animal studies have found that eating cruciferous vegetables may help the body remove toxins, and it may even slow down the progression of fatty liver disease in mice (1).

That said, a 2015 study published in the World Journal of Gastroenterology found that broccoli sprout extract helped to improve liver enzyme levels and decrease oxidative stress in men with fatty liver disease.

If youre looking for the ultimate snack food, then look no further than nuts. High in omega 3 fatty acids, as well as antioxidants and vitamin E, nuts are exactly what your health, and your liver, need.

For one, findings published in the World Journal of Gastroenterology found that, over a six-month period, 106 people with non-alcoholic fatty liver disease experienced improved levels of liver enzymes following their regular consumption of nuts.

Whats more, an observational study published in the Journal ofGastroenterologyandHepatology found a link between men who ate small amounts of nuts and seeds and an increased risk of developing NAFLD.

Olive oil is considered one of the best sources of healthy fat in the world, and this can help to benefit your liver.

Fat accumulation in the liver is one of the first signs of liver disease. That said, research published in the journal Diabetes Care found that consuming a teaspoon of olive oil a day helped not only improve liver enzymes, but also fat levels.

Berries, particularly the deep-hued ones like blueberries, blackberries, and raspberries, are rich in antioxidants known as polyphenols, and these plant compounds may help to protect the liver from damage.

According to an animal study published in the World Journal of Gastroenterology, the antioxidants commonly found in berries helped to slow down the development of scar tissue in the livers of rats.

Additionally, a test-tube study found in the Food Chemistry journal revealed that blueberry extract helped to inhibit the growth of human liver cancer cells.

Thats right. Believe it or not, your morning cup of coffee may be whats keeping your liver so healthy, as a result of its protective properties.

For instance, a study published in the Journal of Clinical Gastroenterologysuggested that coffee helps to reduce fat buildup in the liver. If thats not enough, the same study found that drinking coffee helps to lower the risk of permanent liver damage in people with chronic liver disease. Additionally, a separate study saw that drinking coffee can help reduce the risk of death in people with chronic liver disease (2).

As there are foods that can help to keep your liver healthy, there are also those that may affect its health. These include:

Your liver is a vital organ thats needed for various processes, in order to keep your body healthy. Now, while the efficiency of a traditional liver detox or cleanse is still up for debate, there are foods that can help protect its health.

Read the original post:
Liver Detox: 6 Foods To Boost and Cleanse Your Liver - Longevity LIVE

Your enjoyment of FIFA 20 depended on your patience, longevity with the series and whether or not you do anything with the game other than open Ultimate Team packs.

It was just another year for EA's footy machine, but it didn't roll past without serious flak on YouTube and social media from angry gamers who demanded to know why everything was so stale. Bugs and glitches were popping up all over the place too, and the whole project became 2019's latest reminder that annual franchises might not be worth the cash every time they're pumped out onto store shelves.

At this stage, a year off would be a blessing. That's not going to happen though, and it leads many to worry about what FIFA 21 will bring. This will be the dawn of yet another new era for EA's uncompromising juggernaut, and they're not the only ones vying to make it special. Those who venture beyond FIFA's limits know there's stiff competition for the football gaming crown.

Start chewing those fingernails, FIFA lovers, because there are loads of reasons to fret about what 21 will be like...

Read the original:
FIFA 21: 10 Reasons To Be Worried - WhatCulture

Microsoft co-founder Bill Gates makes a point during a Q&A with Margaret Hamburg, board chair for the American Association for the Advancement of Science. (GeekWire Photo / Alan Boyle)

Microsoft co-founder Bill Gates has been working to improve the state of global health through his nonprofit foundation for 20 years, and today he told the nations premier scientific gathering that advances in artificial intelligence and gene editing could accelerate those improvements exponentially in the years ahead.

We have an opportunity with the advance of tools like artificial intelligence and gene-based editing technologies to build this new generation of health solutions so that they are available to everyone on the planet. And Im very excited about this, Gates said in Seattle during a keynote address at the annual meeting of the American Association for the Advancement of Science.

Such tools promise to have a dramatic impact on several of the biggest challenges on the agenda for the Bill & Melinda Gates Foundation, created by the tech guru and his wife in 2000.

When it comes to fighting malaria and other mosquito-borne diseases, for example, CRISPR-Cas9 and other gene-editing tools are being used to change the insects genome to ensure that they cant pass along the parasites that cause those diseases. The Gates Foundation is investing tens of millions of dollars in technologies to spread those genomic changes rapidly through mosquito populations.

Millions more are being spent to find new ways fighting sickle-cell disease and HIV in humans. Gates said techniques now in development could leapfrog beyond the current state of the art for immunological treatments, which require the costly extraction of cells for genetic engineering, followed by the re-infusion of those modified cells in hopes that theyll take hold.

For sickle-cell disease, the vision is to have in-vivo gene editing techniques, that you just do a single injection using vectors that target and edit these blood-forming cells which are down in the bone marrow, with very high efficiency and very few off-target edits, Gates said. A similar in-vivo therapy could provide a functional cure for HIV patients, he said..

The rapid rise of artificial intelligence gives Gates further cause for hope. He noted that that the computational power available for AI applications has been doubling every three and a half months on average, dramatically improving on the two-year doubling rate for chip density thats described by Moores Law.

One project is using AI to look for links between maternal nutrition and infant birth weight. Other projects focus on measuring the balance of different types of microbes in the human gut, using high-throughput gene sequencing. The gut microbiome is thought to play a role in health issues ranging from digestive problems to autoimmune diseases to neurological conditions.

This is an area that needed these sequencing tools and the high-scale data processing, including AI, to be able to find the patterns, Gates said. Theres just too much going on there if you had to do it, say, with paper and pencil to understand the 100 trillion organisms and the large amount of genetic material there. This is a fantastic application for the latest AI technology.

Similarly, organs on a chip could accelerate the pace of biomedical research without putting human experimental subjects at risk.

In simple terms, the technology allows in-vitro modeling of human organs in a way that mimics how they work in the human body, Gates said. Theres some degree of simplification. Most of these systems are single-organ systems. They dont reproduce everything, but some of the key elements we do see there, including some of the disease states for example, with the intestine, the liver, the kidney. It lets us understand drug kinetics and drug activity.

The Gates Foundation has backed a number of organ-on-a-chip projects over the years, including one experiment thats using lymph-node organoids to evaluate the safety and efficacy of vaccines. At least one organ-on-a-chip venture based in the Seattle area, Nortis, has gone commercial thanks in part to Gates support.

High-tech health research tends to come at a high cost, but Gates argues that these technologies will eventually drive down the cost of biomedical innovation.

He also argues that funding from governments and nonprofits will have to play a role in the worlds poorer countries, where those who need advanced medical technologies essentially have no voice in the marketplace.

If the solution of the rich country doesnt scale down then theres this awful thing where it might never happen, Gates said during a Q&A with Margaret Hamburg, who chairs the AAAS board of directors.

But if the acceleration of medical technologies does manage to happen around the world, Gates insists that could have repercussions on the worlds other great challenges, including the growing inequality between rich and poor.

Disease is not only a symptom of inequality, he said, but its a huge cause.

Other tidbits from Gates talk:

Read Gates prepared remarks in a posting to his Gates Notes blog, or watch the video on AAAS YouTube channel.

Excerpt from:
Why Bill Gates thinks gene editing and artificial intelligence could save the world - GeekWire

In recent years, promising start-ups have faced almost no obstacles to raising capital, so long as they pursued growth at all costs. Investors accepted significant losses in the present on the premise that these would translate to incredible market share in the future. The environment of easy money created many questionable valuations (see: WeWork), and even rare instances of outright fraud (see: Theranos).

But the market shifted in 2019. Investors are thinking more objectively about the stories presented by start-ups and emerging companies, and are much more interested in profitable growth, or at least progress toward it, than empty promises of a big payoff down the road.

While tech companies such as WeWork, Uber, Slack Technologies, and others have been hit by this newfound skepticism, even swearing off the growth-at-all-costs mantra of years past, the field of synthetic biology has yet to (publicly) face its reckoning. If and when it does, Twist Bioscience (NASDAQ:TWST) might be the first to fall.

Image source: Getty Images

Twist Bioscience wields the leading technology platform for synthesizing DNA, which can be used in genetic engineering experiments to create reference probes for DNA sequencing applications and to store digital data. The company is often associated with synthetic biology, or engineered biology, which is the intentional design of living technologies with reproducible functionality.

The company recently reported fiscal first-quarter 2020 operating results for the three-month period ending Dec. 31, and announced it had settled a long-standing legal dispute with Agilent Technologies. The settlement avoided a costly jury trial, but cost the synthetic DNA pioneer $22.5 million. Investors were just pleased to be rid of the headache, and to have removed the largest source of uncertainty hanging over the stock. Shares soared on the announcement.

The immediate interpretation of this event is that the settlement will allow Twist Bioscience and Wall Street to focus entirely on growth and financial performance. A deeper dive, however, suggests investors might want to be careful what they wish for.

While the company touts impressive growth in revenue and gross profit, that means little when losses attributed to shareholders are growing even faster in absolute dollar amounts. Operating losses have now grown sequentially for eight consecutive quarters.

Metric

Fiscal Q1 2020

Fiscal Q1 2019

Change (YoY)

Revenue

$17.2 million

$11.5 million

49%

Gross profit

$3.3 million

($0.4 million)

N/A

Operating expenses

$59.2 million

$22.5 million

163%

Operating expenses excluding Agilent settlement

$36.7 million

$22.5 million

63%

Operating income

($55.8 million)

($22.9 million)

N/A

Operating income excluding Agilent settlement

($33.3 million)

($22.9 million)

N/A

Data source: Twist Bioscience press release. YoY = Year over Year.

When the Agilent legal settlement is excluded, normal day-to-day operations resulted in fiscal first-quarter 2020 operating expenses of $36.7 million. That was $14.2 million greater than in the year-ago period, which easily offset the $3.7 million improvement in gross profit in that span.

Swelling losses have had a real impact on shareholders: dilution. Twist Bioscience has tapped into the public markets multiple times since conducting its initial public offering (IPO) in late 2018, including an offering in late January that raised $48.2 million in net proceeds. Investors now know that was largely conducted to pay for the Agilent legal settlement, which will consume roughly half of the proceeds.

In a little over 15 months as a publicly traded company, multiple stock offerings from Twist Bioscience have increased the number of shares outstanding from 26.6 million to 35.4 million. That's an increase of 33%. Considering the business reported $103 million in cash at the end of December and expects to report a net loss of at least $129.5 million in fiscal 2020, investors should expect additional public stock offerings or convertible debt offerings -- and, therefore, additional dilution -- in the near future.

It might be tempting to think the company could just flip a switch and focus on profitable growth, but a closer look at SEC filings suggests that might not be possible.

Image source: Getty Images

Investors know Twist Bioscience as the company that makes synthetic DNA. It serves industrial and pharmaceutical customers that require (relatively) large amounts of DNA for high-throughput genetic engineering research. It's by far the best in the industry -- even supplying some of its competitors.

However, most of the company's growth and profits come from an entirely different market: next-generation sequencing (NGS) tools. In fact, NGS tools are expected to generate nearly as much revenue in fiscal 2020 as synthetic genes. It's a bit ironic that the company known for writing DNA is increasingly dependent on companies that read DNA, but there are two primary reasons for that.

First, despite all of the hype, the market for synthetic DNA is simply not very large and isn't very profitable (if it's profitable at all). Roughly 25% of the company's synthetic gene revenue in fiscal 2020 will come from a single customer. It's also worth noting that the business didn't begin generating gross profit until it ramped up sales of NGS tools.

Second, Twist Bioscience's technology platform is well suited for designing NGS tools. The company uses its ability to synthesize accurate DNA sequences to create high-quality target enrichment probes, which allow researchers to detect specific genetic sequences in biological samples.

But investors cannot conflate early success in the NGS market with being on the path to profitability. Sales of target enrichment probes are far from sufficient to offset losses from the remainder of the business. The company expects roughly half of fiscal full-year 2020 revenue to come from money-losing or low-margin products related to synthetic genes; the other half will comprise NGS tools.

Revenue Category

Fiscal Full-Year 2020 Revenue Guidance

Fiscal Full-Year 2019 Revenue, Actual

Change (YoY)

Synthetic genes and related products

$42 million to $43 million

$33.3 million

26% to 29%

NGS tools

$37 million to $40 million

$21.0 million

67% to 76%

Biopharma collaboration

$1 million

N/A

N/A

Total revenue

$80 million to $84 million

$54.4 million

47% to 54%

Data source: Twist Bioscience. YoY = Year over Year.

Despite impressive revenue growth, Twist Bioscience expects to report a net loss of at least $107 million from day-to-day operations in the current fiscal year. That's exactly the same net loss reported in fiscal 2019, and it jumps to at least $129.5 million when the Agilent legal settlement is included.

That also suggests that Twist Bioscience might be stuck financially for the foreseeable future. In order toremain relevant in a money-losing market for synthetic genes and a very competitive market for NGS tools, it must spend significant sums of money on sales and marketing expenses, which are the main driver of operating losses.

In other words, although NGS products are responsible for most of the company's gross profit, they're also responsible for much of the company's operating losses. If the company stopped marketing its products as heavily in an attempt to pare losses, then it might not grow quickly enough to achieve breakeven operations. That suggests Twist Bioscience is pursuing growth at all costs because it doesn't really have any other options. That's not a very secure position for individual investors.

Image source: Getty Images

Investors might be drawn to Twist Bioscience because of its industry-leading technology platform for synthesizing DNA. It can create products today for high-throughput genetic engineering experiments or NGS tools, while tomorrow's opportunities could span digital data storage in DNA or rational design of biologic drugs.

But, to be blunt, publicly traded synthetic biology companies have a downright awful track record of living up to their lofty promises. The best product from the field to date has been hype, and that's led to terrible outcomes for individual investors who invested on storytelling alone. Shares of Twist Bioscience have rewarded investors with solid gains since the IPO, but swelling losses make it reasonable to question if and when the sentiment will turn negative.

Continued here:
Twist Bioscience Pursues Growth at All Costs. How Long Will Investors Tolerate It? - Motley Fool

(KTSDESIGN/Science Photo Library)

Science issues whether connected with climate, childhood vaccines or new techniques in biotechnology are part of the fabric of civic life, raising a range of social, ethical and policy issues for the citizenry. As members of the scientific community gather at the annual meeting of the American Association for the Advancement of Science (AAAS) this week, here is a roundup of key takeaways from our studies of U.S. public opinion about science issues and their effect on society. If youre on Twitter, follow @pewscience for more science findings.

The data for this post was drawn from multiple different surveys. The most recent was a survey of 3,627 U.S. adults conducted Oct. 1 to Oct. 13, 2019. This post also draws on data from surveys conducted in January 2019, December 2018, April-May 2018 and March 2016. All surveys were conducted using the American Trends Panel (ATP), an online survey panel that is recruited through national, random sampling of residential addresses. This way nearly all U.S. adults have a chance of being selected. The survey is weighted to be representative of the U.S. adult population by gender, race, ethnicity, education and other categories. Read more about the ATPs methodology.

Following are the questions and responses for surveys used in this post, as well as each surveys methodology:

1Some public divides over science issues are aligned with partisanship, while many others are not. Science issues can be a key battleground for facts and information in society. Climate science has been part of an ongoing discourse around scientific evidence, how to attribute average temperature increases in the Earths climate system, and the kinds of policy actions needed. While public divides over climate and energy issues are often aligned with political party affiliation, public attitudes on other science-related issues are not.

For example, there are differences in public beliefs around the risks and benefits of childhood vaccines. Such differences arise amid civic debates about the spread of false information about vaccines. While such beliefs have important implications for public health, they are not particularly political in nature.

In fact, Republicans and independents who lean to the GOP are just as likely as Democrats and independents who lean to the Democratic Party to say that, overall, the benefits of the measles, mumps and rubella vaccine outweigh the risks (89% and 88% respectively).

2Americans have differing views about some emerging scientific and technological developments. Scientific and technological developments are a key source of innovation and, therefore, change in society. Pew Research Center studies have explored public reactions to emergent developments from genetic engineering techniques, automation and more. One field at the forefront of public reaction is the use of gene editing of babies or genetic engineering of animals. Americans have mixed views over whether the use of gene editing to reduce a babys risk of serious disease that could occur over their lifetime is appropriate (60%) or is taking medical technology too far (38%), according to a 2018 survey. Similarly, about six-in-ten Americans (57%) said that genetic engineering of animals to grow organs or tissues for humans needing a transplant would be appropriate, while four-in-ten (41%) said it would be taking technology too far.

When we asked Americans about a future where a brain chip implant would give otherwise healthy individuals much improved cognitive abilities, a 69% majority said they were very or somewhat worried about the possibility. By contrast, about half as many (34%) were enthusiastic. Further, as people think about the effects of automation technologies in the workplace, more say automation has brought more harm than help to American workers.

One theme running through our findings on emerging science and technology is that public hesitancy often is tied to concern about the loss of human control, especially if such developments would be at odds with personal, religious and ethical values. In looking across seven developments related to automation and the potential use of biomedical interventions to enhance human abilities, Center studies found that proposals that would increase peoples control over these technologies were met with greater acceptance.

3Most in the U.S. see net benefits from science for society, and they expect more ahead. About three-quarters of Americans (73%) say science has, on balance, had a mostly positive effect on society. And 82% expect future scientific developments to yield benefits for society in years to come.

The overall portrait is one of strong public support for the benefits of science to society, though the degree to which Americans embrace this idea differs sizably by race and ethnicity as well as by levels of science knowledge.

Such findings are in line with those of the General Social Survey on the effects of scientific research. In 2018, about three-quarters of Americans (74%) said the benefits of scientific research outweigh any harmful results. Support for scientific research by this measure has been roughly stable since the 1980s.

4The share of Americans with confidence in scientists to act in the public interest has increased since 2016.

Public confidence in scientists to act in the public interest tilts positive and has increased over the past few years. As of 2019, 35% of Americans report a great deal of confidence in scientists to act in the public interest, up from 21% in 2016.

About half of the public (51%) reports a fair amount of confidence in scientists, and just 13% have not too much or no confidence in this group to act in the public interest.

Public trust in scientists by this measure stands in contrast to that for other groups and institutions. One of the hallmarks of the current times has been low trust in government and other institutions. One-in-ten or fewer say they have a great deal of confidence in elected officials (4%) or the news media (9%) to act in the public interest.

5Americans differ over the role and value of scientific experts in policy matters. While confidence in scientists overall tilts positive, peoples perspectives about the role and value of scientific experts on policy issues tends to vary. Six-in-ten U.S. adults believe that scientists should take an active role in policy debates about scientific issues, while about four-in-ten (39%) say, instead, that scientists should focus on establishing sound scientific facts and stay out of such debates.

Democrats are more inclined than Republicans to think scientists should have an active role in science policy matters. Indeed, most Democrats and Democratic-leaning independents (73%) hold this position, compared with 43% of Republicans and GOP leaners.

More than four-in-ten U.S. adults (45%) say that scientific experts usually make better policy decisions than other people, while a similar share (48%) says such decisions are neither better nor worse than other peoples and 7% say scientific experts decisions are usually worse than other peoples.

Here, too, Democrats tend to hold scientific experts in higher esteem than do Republicans: 54% of Democrats say scientists policy decisions are usually better than those of other people, while two-thirds of Republicans (66%) say that scientists decisions are either no different from or worse than other peoples.

6Factual knowledge alone does not explain public confidence in the scientific method to produce sound conclusions. Overall, a 63% majority of Americans say the scientific method generally produces sound conclusions, while 35% think it can be used to produce any result a researcher wants. Peoples level of knowledge can influence beliefs about these matters, but it does so through the lens of partisanship, a tendency known as motivated reasoning.

Beliefs about this matter illustrate that science knowledge levels sometimes correlate with public attitudes. But partisanship has a stronger role.

Democrats are more likely to express confidence in the scientific method to produce accurate conclusions than do Republicans, on average. Most Democrats with high levels of science knowledge (86%, based on an 11-item index of factual knowledge questions) say the scientific method generally produces accurate conclusions. By comparison, 52% of Democrats with low science knowledge say this. But science knowledge has little bearing on Republicans beliefs about the scientific method.

7Trust in practitioners like medical doctors and dietitians is stronger than that for researchers in these fields, but skepticism about scientific integrity is widespread. Scientists work in a wide array of fields and specialties. A 2019 Pew Research Center survey found public trust in medical doctors and dietitians to be higher than that for researchers working in these areas. For example, 48% of U.S. adults say that medical doctors give fair and accurate information all or most of the time. By comparison, 32% of U.S. adults say the same about medical research scientists. And six-in-ten Americans say dietitians care about their patients best interests all or most of the time, while about half as many (29%) say this about nutrition research scientists with the same frequency.

One factor in public trust of scientists is familiarity with their work. For example, people who were more familiar with what medical science researchers do were more trusting of these researchers to express care or concern for the public interest, to do their job with competence and to provide fair and accurate information. Familiarity with the work of scientists was related to trust for all six specialties we studied.

But when it comes to questions of scientists transparency and accountability, most Americans are skeptical. About two-in-ten or fewer U.S. adults say that scientists are transparent about potential conflicts of interest with industry groups all or most of the time. Similar shares (roughly between one-in-ten and two-in-ten) say that scientists admit their mistakes and take responsibility for them all or most of the time.

This data shows clearly that when it comes to questions of transparency and accountability, most in the general public are attuned to the potential for self-serving interests to skew science findings and recommendations. These findings echo calls for increased transparency and accountability across many sectors and industries today.

8What boosts public trust in scientific research findings? Most say its making data openly available. A 57% majority of Americans say they trust scientific research findings more when the data is openly available to the public. And about half of the U.S. public (52%) say they are more likely to trust research that has been independently reviewed.

The question of who funds the research is also consequential for how people think about scientific research. A 58% majority say they have lower trust when research is funded by an industry group. By comparison, about half of Americans (48%) say government funding for research has no particular effect on how much they trust the findings; 28% say this decreases their trust and 23% say it increases their trust.

Originally posted here:
Key findings about Americans' confidence in science and their views on scientists' role in society - Pew Research Center

Lee Greenberger, chief scientific officer at the Leukemia and Lymphoma Society, discusses the use of immunotherapy in blood cancer treatment.

BY Kristie L. Kahl and Lee Greenberger

Transcript:

Kristie L. Kahl: Can you give us a background on what immunotherapy is and how it works?

Lee Greenberger: Immunotherapy has a long history in blood cancer. It goes all the way back to transplantations where you take the immune cells from one patient and put it into the other. It actually can end up being curative in that transplant situation. We now know the molecular basis of that, and immunotherapy has evolved considerably, specifically in the last 10 years where we have sort of brought it out of the lab and now moving it forward.

The story begins with monoclonal antibodies and (Rituxan [rituximab]), which is a monoclonal antibody to CD20, which sits on the surface of tumor cells. It was one of the first antibodies approved, along with (Herceptin [trastuzumab]) for breast cancer. Rituxan is used for blood cancers and used widely. So, the concept that you can make antibodies in the laboratory, manufacture them, bring them out to patients and it has shown that it is highly effective in multiple lymphomas. Since that time, there are multiple antibodies that have come out.

Beyond that, in the last 10 years in particular, we now know that there are all sorts of mechanisms control the immune system, and in fact, the immune system is highly effective at getting rid of tumor cells. For example, in the late 1980s, there was an investigator in Israel who figured out how to actually manufacture from scratch, a gene and put it into T cells, which would allow the T cells, which are part of the immune system, to home on the tumor cells and kill those cells. That evolved into something called chimeric antigen receptor-therapy, or CAR-T. CAR-T has gone through multiple evolutions, but there are now two CAR-T products on the market, and basically what this is a genetic engineering of the T cells.

You take the T cells out of the patient, genetically engineer that gene, put it into those T cells, and now that T cell can home on the tumor cell. When it arrives at the tumor cell, it is recognizing something very specific on those tumor cells. It will dramatically expand. So, instead of having one T cell, now youll have a million cells. And those cells can very effectively kill tumor cells for certain patients. For example, its been used very effectively in children with B-cell type leukemia. Its also used in certain types of lymphoma, most notably diffuse large B cell lymphoma and recently mantle cell lymphoma.

So, thats one type. The cells have to come out of the patient. Manufacturing takes about 14-21 days, and put back into the patient. That can be a very effective solution for treating patients with relapsed disease.

Along with CAR-T cell therapy, there is bi-specific antibodies. These are antibodies that are capable of taking the T cells of the patient and making them recognize the tumor cells. So, instead of a linker that will move these cells together, hence the notion of bi-specific: one to the tumor cells, one to the T cells, bring them together and it makes the T cells capable of killing the tumor cells.

You also have antibody drug conjugates. In that case, you take an antibody which is going to home in on the surface of the tumor cells, and you link it to a toxin. This technology is actually quite fascinating because it actually grew up about the same time that monoclonal antibodies were developed. We had a bunch of super toxins discovered from products. They were so toxic they couldnt even be used by themselves, but if you take that toxin and link it to an antibody, now you have a guided missile. The antibody arrives at the tumor cell, brings the toxin into the tumor cell. Antibody drug conjugates have been on the market since the late 1990s.

Bottom line is, the reason why immunotherapy is so attractive is because it specifically homes on the tumor cell, its highly effective at killing the tumor cell, and it doesnt have some of the harsh, toxic side effects that cytotoxic drugs typically do. Thats not to say they are devoid of toxicity, but its of a different nature and it in general can be managed well.

Kristie L. Kahl: What are some of the more notable side effects?

Lee Greenberger: For CAR-T cell therapy, which is among the most advanced, you get something called cytokine release syndrome. These T cells basically become so revved up, that they secrete a lot of cytokine products that can make you feel ill, cause fever, and in rare cases can be lethal if you cant control them. So, they can compromise organs. Physicians nowadays with CAR-T cell therapy are well aware of some of these cytokine release syndrome (symptoms). They tend to appear a few days after therapy, and dont last for very long but you have to recognize that theyre there. Its a very common event for CAR-T cell therapy. Were getting better at these things. They used to be grade 3, which is serious, now some of the new CAR-T cell therapies are having low-grade (side effects), which do not require observation.

Neurotoxicity is another, where the patient may be disoriented. This also comes up as the T cell numbers increase dramatically, the neurotoxicity could manifest as confusion, disorientation, and then it will die away over time, generally over a couple of weeks.

So, those are two things to watch out for for CAR-T cell therapy. Theyre manageable, but it can be of a serious nature.

Kristie L. Kahl: How does the multidisciplinary approach play a role?

Lee Greenberger:CAR-T cell therapy requires the involvement of many people in the treatment. There are cells that have to come out of the patient, where you take the blood out of the patient and harvest the cells, so there are technicians involved harvesting the cells. Then they go out to a laboratory, and they will make them in their labs. The cells go back into the patient, and that requires careful observation, typically for the next week after you get these cells. This can require an in-hospital stay or outpatient. It requires a physician overseeing it, nurses who are qualified to recognize some of the early symptoms, careful monitoring. We can monitor these things because we know we have biomarkers to know how aggressive these T cells are expanding. So, for example, for cytokine release syndrome, IL6 levels can shoot way high. So, if you are analyzing the blood, and can get these results back quickly, we now have therapies to knock down the IL6 levels and block those effects.

Kristie L. Kahl: What are some questions patients can ask their doctors so that they can become better informed about their treatment decisions?

Lee Greenberger: The road to treating these blood cancers is actually a long, involved road. In some cases, some blood cancers require watch-and-wait and we dont do anything. In other cases, a newly diagnosed patient will begin to get treatment, which depends on (the type of blood cancer). The treatments are all quite different. In some of those cases, the initial treatment will keep the patient in check for years. Dont forget that many of these blood cancers happen in older patients (60-70 years old). So, if you can keep the disease in check for 20 years, youre doing fine. In other cases, these lymphomas will come back. Even with CAR-T therapy, where we can control the disease long-term as best as we can, we can expect that a certain number of these patients, the disease will return. So, with relapsed or refractory disease, these are the ones that are going to require additional treatments.

Transcript Edited for Clarity

Link:
The Use of Immunotherapy in Blood Cancer Treatment - Curetoday.com

2/13/20

Hannah Boucher | Staff Columnist

Mass-produced bananas are dying at an increasingly faster rate and are at risk of one day going extinct.

Genetically modified organisms (GMOs) are not as new of a concept as many would like to believe. While it has been a controversial scientific advancement since the 1970s, when Herbert Boyer and Stanley Cohen invented modern-day genetic engineering, artificial selection has been used to cultivate crops and animals for over 30,000 years.

The misconception that GMOs are dangerous has derived from a misunderstanding of the definition. In fact, agriculture exists because humans selectively bred organisms to cater to their needs. This is the definition of agriculture.

Genetic engineering the true controversial topic falls under the umbrella of genetic modification, which is what has brought society its big, red tomatoes, giant ears of yellow corn and sweet bananas.

The technology used to genetically engineer common produce can also be used on animals and bacteria. Cloning and gene transfer have been successfully carried out in scientific labs, however, these successes have been met with much concern.

While humans possess the power to multiply livestock by the masses, or create an entirely new species in a lab, that does not mean it should be done. These processes violate certain ethical standards because they are seen as being humane which is technically true.

An example of this issue is the banana industry. The Cavendish banana which is actually the second species commercially grown fell victim to Panama disease, a fungus that spreads quickly and kills the entire plant. Bananas are mass produced by corporations such as Dole and Chiquita to appeal to the millions but at a cost.

Scientists are struggling to find a banana plant that carries the gene that fights the disease to breed with the Cavendish. Banana plants are now dying at a faster rate than can be produced, meaning that they may go extinct. This is not the first occurrence of this issue either. In the 1950s, the first species of banana, the Gros Michael, was completely wiped out from a strain of the Panama disease.

The main difference between normal cultivation and monoculture is that monoculture decreases the variability within a population. Cultivation has been successfully practiced for thousands of years. Some of the most commonly consumed vegetables are actually all derived from the same species. Broccoli, cabbage, kale, brussel sprouts and a few other popular greens are all cultivated forms of Brassica oleracea, or, wild cabbage.

Although there are major risks associated with selective breeding, there are also major benefits. By selective the most favorable traits within a species, the fitness, or the species ability to produce viable offspring, increases.

This has helped the farming industry keep up with the growing pool of consumers that continues to increase as the population rises. Certain modifications reduce the need for pesticides and increase the overall crop yield, which also increases the overall income for farmers.

Another big issue with GMOs is that not all of the health risks are currently known. Before any new modified products are released to consumers, they must undergo a series of tests assessing the possible hazards posed from consumption. However, the regulations put in place by the Center for Food Safety [CFS] require all products that contain genetically engineered ingredients to be clearly labeled so people are aware of its contents.

It is important to consider though that many technological advancements pose risks to the general public. It is not the act of genetically manipulating an organism that is the problem, but rather the lack of consideration of the possible issues. Scientists must be careful not to cross a line because they hold the fate of species in their hands. There is nothing to fear when it comes to GMOs. Civilization would be nonexistent without the cultivation of crops and animals.

Related

Visit link:
Public fears and anxieties over GMOs growing old - The Duquesne Duke

Such is the extent of our dominion on Earththat the answers to questions around whether we are still part of nature and whether we even need some of it rely on an understanding of what we want as Homo sapiens. And to know what we want, we need to grasp what we are.

It is a huge question but they are the best. And as a biologist, here is my humble suggestion to address it, and a personal conclusion. You may have a different one, but what matters is that we reflect on it.

Perhaps the best place to start is to consider what makes us human in the first place, which is not as obvious as it may seem.

Sharing the full story, not just the headlines

Many years ago, a novel written by Vercors called Les Animaux Dnaturs (Denatured Animals) told the story of a group of primitive hominids, the Tropis, found in an unexplored jungle in New Guinea, who seem to constitute a missing link. However, the prospect that this fictional group may be used as slave labour by an entrepreneurial businessman named Vancruysen forces society to decide whether the Tropis are simply sophisticated animals or whether they should be given human rights. And herein lies the difficulty.

Human status had hitherto seemed so obvious that the book describes how it is soon discovered that there is no definition of what a human actually is. Certainly, the string of experts consulted anthropologists, primatologists, psychologists, lawyers and clergymen could not agree. Perhaps prophetically, it is a layperson who suggested a possible way forward.

She asked whether some of the hominids habits could be described as the early signs of a spiritual or religious mind. In short, were there signs that, like us, the Tropis were no longer at one with nature, but had separated from it, and were now looking at it from the outside with some fear.

Pluto has a 'beating heart' of frozen nitrogen that is doing strange things to its surface, Nasa has found.The mysterious core seems to be the cause of features on its surface that have fascinated scientists since they were spotted by Nasa's New Horizons mission."Before New Horizons, everyone thought Pluto was going to be a netball - completely flat, almost no diversity," said Tanguy Bertrand, an astrophysicist and planetary scientist at NASA's Ames Research Center and the lead author on the new study."But it's completely different. It has a lot of different landscapes and we are trying to understand what's going on there."

Getty

The ancient invertabrate worm-like species rhenopyrgus viviani (pictured) is one of over 400 species previously unknown to science that were discovered by experts at the Natural History Museum this year

PA

Jackdaws can identify dangerous humans from listening to each others warning calls, scientists say. The highly social birds will also remember that person if they come near their nests again, according to researchers from the University of Exeter. In the study, a person unknown to the wild jackdaws approached their nest. At the same time scientists played a recording of a warning call (threatening) or contact calls (non-threatening). The next time jackdaws saw this same person, the birds that had previously heard the warning call were defensive and returned to their nests more than twice as quickly on average.

Getty

The sex of the turtle is determined by the temperatures at which they are incubated. Warm temperatures favour females.But by wiggling around the egg, embryos can find the Goldilocks Zone which means they are able to shield themselves against extreme thermal conditions and produce a balanced sex ratio, according to the new study published in Current Biology journal

Ye et al/Current Biology

African elephant poaching rates have dropped by 60 per cent in six years, an international study has found. It is thought the decline could be associated with the ivory trade ban introduced in China in 2017.

Reuters

Scientists have identified a four-legged creature with webbed feet to be an ancestor of the whale. Fossils unearthed in Peru have led scientists to conclude that the enormous creatures that traverse the planets oceans today are descended from small hoofed ancestors that lived in south Asia 50 million years ago

A. Gennari

A scientist has stumbled upon a creature with a transient anus that appears only when it is needed, before vanishing completely. Dr Sidney Tamm of the Marine Biological Laboratory could not initially find any trace of an anus on the species. However, as the animal gets full, a pore opens up to dispose of waste

Steven G Johnson

Feared extinct, the Wallace's Giant bee has been spotted for the first time in nearly 40 years. An international team of conservationists spotted the bee, that is four times the size of a typical honeybee, on an expedition to a group of Indonesian Islands

Clay Bolt

Fossilised bones digested by crocodiles have revealed the existence of three new mammal species that roamed the Cayman Islands 300 years ago. The bones belonged to two large rodent species and a small shrew-like animal

New Mexico Museum of Natural History

Scientists at the University of Maryland have created a fabric that adapts to heat, expanding to allow more heat to escape the body when warm and compacting to retain more heat when cold

Faye Levine, University of Maryland

A study from the University of Tokyo has found that the tears of baby mice cause female mice to be less interested in the sexual advances of males

Getty

The Intergovernmental Panel on Climate Change has issued a report which projects the impact of a rise in global temperatures of 1.5 degrees Celsius and warns against a higher increase

Getty

The nobel prize for chemistry has been awarded to three chemists working with evolution. Frances Smith is being awarded the prize for her work on directing the evolution of enzymes, while Gregory Winter and George Smith take the prize for their work on phage display of peptides and antibodies

Getty/AFP

The nobel prize for physics has been awarded to three physicists working with lasers. Arthur Ashkin (L) was awarded for his "optical tweezers" which use lasers to grab particles, atoms, viruses and other living cells. Donna Strickland and Grard Mourou were jointly awarded the prize for developing chirped-pulse amplification of lasers

Reuters/AP

The Ledumahadi Mafube roamed around 200 million years ago in what is now South Africa. Recently discovered by a team of international scientists, it was the largest land animal of its time, weighing 12 tons and standing at 13 feet. In Sesotho, the South African language of the region in which the dinosaur was discovered, its name means "a giant thunderclap at dawn"

Viktor Radermacher / SWNS

Scientists have witnessed the birth of a planet for the first time ever. This spectacular image from the SPHERE instrument on ESO's Very Large Telescope is the first clear image of a planet caught in the very act of formation around the dwarf star PDS 70. The planet stands clearly out, visible as a bright point to the right of the center of the image, which is blacked out by the coronagraph mask used to block the blinding light of the central star.

ESO/A. Mller et al

Layers long thought to be dense, connective tissue are actually a series of fluid-filled compartments researchers have termed the interstitium. These compartments are found beneath the skin, as well as lining the gut, lungs, blood vessels and muscles, and join together to form a network supported by a mesh of strong, flexible proteins

Getty

Working in the Brazilian state of Mato Grosso, a team led by archaeologists at the University of Exeter unearthed hundreds of villages hidden in the depths of the rainforest. These excavations included evidence of fortifications and mysterious earthworks called geoglyphs

Jos Iriarte

More than one in 10 people were found to have traces of class A drugs on their fingers by scientists developing a new fingerprint-based drug test.Using sensitive analysis of the chemical composition of sweat, researchers were able to tell the difference between those who had been directly exposed to heroin and cocaine, and those who had encountered it indirectly.

Getty

The storm bigger than the Earth, has been swhirling for 350 years. The image's colours have been enhanced after it was sent back to Earth.

Pictures by: Tom Momary

Pluto has a 'beating heart' of frozen nitrogen that is doing strange things to its surface, Nasa has found.The mysterious core seems to be the cause of features on its surface that have fascinated scientists since they were spotted by Nasa's New Horizons mission."Before New Horizons, everyone thought Pluto was going to be a netball - completely flat, almost no diversity," said Tanguy Bertrand, an astrophysicist and planetary scientist at NASA's Ames Research Center and the lead author on the new study."But it's completely different. It has a lot of different landscapes and we are trying to understand what's going on there."

Getty

The ancient invertabrate worm-like species rhenopyrgus viviani (pictured) is one of over 400 species previously unknown to science that were discovered by experts at the Natural History Museum this year

PA

Jackdaws can identify dangerous humans from listening to each others warning calls, scientists say. The highly social birds will also remember that person if they come near their nests again, according to researchers from the University of Exeter. In the study, a person unknown to the wild jackdaws approached their nest. At the same time scientists played a recording of a warning call (threatening) or contact calls (non-threatening). The next time jackdaws saw this same person, the birds that had previously heard the warning call were defensive and returned to their nests more than twice as quickly on average.

Getty

The sex of the turtle is determined by the temperatures at which they are incubated. Warm temperatures favour females.But by wiggling around the egg, embryos can find the Goldilocks Zone which means they are able to shield themselves against extreme thermal conditions and produce a balanced sex ratio, according to the new study published in Current Biology journal

Ye et al/Current Biology

African elephant poaching rates have dropped by 60 per cent in six years, an international study has found. It is thought the decline could be associated with the ivory trade ban introduced in China in 2017.

Reuters

Scientists have identified a four-legged creature with webbed feet to be an ancestor of the whale. Fossils unearthed in Peru have led scientists to conclude that the enormous creatures that traverse the planets oceans today are descended from small hoofed ancestors that lived in south Asia 50 million years ago

A. Gennari

A scientist has stumbled upon a creature with a transient anus that appears only when it is needed, before vanishing completely. Dr Sidney Tamm of the Marine Biological Laboratory could not initially find any trace of an anus on the species. However, as the animal gets full, a pore opens up to dispose of waste

Steven G Johnson

Feared extinct, the Wallace's Giant bee has been spotted for the first time in nearly 40 years. An international team of conservationists spotted the bee, that is four times the size of a typical honeybee, on an expedition to a group of Indonesian Islands

Clay Bolt

Fossilised bones digested by crocodiles have revealed the existence of three new mammal species that roamed the Cayman Islands 300 years ago. The bones belonged to two large rodent species and a small shrew-like animal

New Mexico Museum of Natural History

Scientists at the University of Maryland have created a fabric that adapts to heat, expanding to allow more heat to escape the body when warm and compacting to retain more heat when cold

Faye Levine, University of Maryland

A study from the University of Tokyo has found that the tears of baby mice cause female mice to be less interested in the sexual advances of males

Getty

The Intergovernmental Panel on Climate Change has issued a report which projects the impact of a rise in global temperatures of 1.5 degrees Celsius and warns against a higher increase

Getty

The nobel prize for chemistry has been awarded to three chemists working with evolution. Frances Smith is being awarded the prize for her work on directing the evolution of enzymes, while Gregory Winter and George Smith take the prize for their work on phage display of peptides and antibodies

Getty/AFP

The nobel prize for physics has been awarded to three physicists working with lasers. Arthur Ashkin (L) was awarded for his "optical tweezers" which use lasers to grab particles, atoms, viruses and other living cells. Donna Strickland and Grard Mourou were jointly awarded the prize for developing chirped-pulse amplification of lasers

Reuters/AP

The Ledumahadi Mafube roamed around 200 million years ago in what is now South Africa. Recently discovered by a team of international scientists, it was the largest land animal of its time, weighing 12 tons and standing at 13 feet. In Sesotho, the South African language of the region in which the dinosaur was discovered, its name means "a giant thunderclap at dawn"

Viktor Radermacher / SWNS

Scientists have witnessed the birth of a planet for the first time ever. This spectacular image from the SPHERE instrument on ESO's Very Large Telescope is the first clear image of a planet caught in the very act of formation around the dwarf star PDS 70. The planet stands clearly out, visible as a bright point to the right of the center of the image, which is blacked out by the coronagraph mask used to block the blinding light of the central star.

ESO/A. Mller et al

Layers long thought to be dense, connective tissue are actually a series of fluid-filled compartments researchers have termed the interstitium. These compartments are found beneath the skin, as well as lining the gut, lungs, blood vessels and muscles, and join together to form a network supported by a mesh of strong, flexible proteins

Getty

Working in the Brazilian state of Mato Grosso, a team led by archaeologists at the University of Exeter unearthed hundreds of villages hidden in the depths of the rainforest. These excavations included evidence of fortifications and mysterious earthworks called geoglyphs

Jos Iriarte

More than one in 10 people were found to have traces of class A drugs on their fingers by scientists developing a new fingerprint-based drug test.Using sensitive analysis of the chemical composition of sweat, researchers were able to tell the difference between those who had been directly exposed to heroin and cocaine, and those who had encountered it indirectly.

Getty

The storm bigger than the Earth, has been swhirling for 350 years. The image's colours have been enhanced after it was sent back to Earth.

Pictures by: Tom Momary

It is a telling perspective. Our status as altered or denatured animals creatures who have arguably separated from the natural world is perhaps both the source of our humanity and the cause of many of our troubles. In the words of the books author:

All mans troubles arise from the fact that we do not know what we are and do not agree on what we want to be

We will probably never know the timing of our gradual separation from nature although cave paintings perhaps contain some clues. But a key recent event in our relationship with the world around us is as well documented as it was abrupt. It happened on a sunny Monday morning, at precisely 8.15am.

A new age

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The atomic bomb that rocked Hiroshima on 6 August 1945 was a wake-up call so loud that it still resonates in our consciousness many decades later.

The day the sun rose twice was not only a forceful demonstration of the new era that we had entered buta reminder of how paradoxically primitive we remained: differential calculus, advanced electronics and almost godlike insights into the laws of the universe helped build, well a very big stick. Modern Homo sapiens seemingly had developed the powers of gods, while keeping the psyche of a stereotypical Stone Age killer.

We were no longer fearful of nature, but of what we would do to it, and ourselves. In short, we still did not know where we came from but began panicking about where we were going. We now know a lot more about our origins but we remain unsure about what we want to be in the future or, increasingly, as the climate crisis accelerates, whether we even have one.

Arguably, the greater choices granted by our technological advances make it even more difficult to decide which of the many paths to take. This is the cost of freedom. I am not arguing against our dominion over nature nor, even as a biologist, do I feel a need to preserve the status quo. Big changes are part of our evolution. After all, oxygen was first a poison which threatened the very existence of early life, yet it is now the fuel vital to our existence.

Similarly, we may have to accept that what we do, even our unprecedented dominion, is a natural consequence of what we have evolved into, and by a process nothing less natural than natural selection itself. If artificial birth control is unnatural, so is reduced infant mortality.

I am also not convinced by the argument against genetic engineering on the basis that it is unnatural. By artificially selecting specific strains of wheat or dogs, we had been tinkering more or less blindly with genomes for centuries before the genetic revolution. Even our choice of romantic partner is a form of genetic engineering. Sex is natures way of producing new genetic combinations quickly.

Even nature, it seems, can be impatient with itself.

Changing our world

Continue reading here:
Have humans evolved beyond nature? - The Independent

The world is watching with alarm as China struggles to contain a dangerous new virus, now being called SARS-CoV-2. It has quarantined entire cities, and the US has put a blanket ban on travellers whove been there. Health officials are scrambling to understand how the virus is transmitted and how to treat patients.

But in one University of North Carolina lab, theres a different race. Researchers are trying to create a copy of the virus. From scratch.

Led by Ralph Baric, an expert in coronaviruseswhich get their name from the crown-shaped spike they use to enter human cellsthe North Carolina team expects to recreate the virus starting only from computer readouts of its genetic sequence posted online by Chinese labs last month.

The remarkable ability to boot up viruses from genetic instructions is made possible by companies that manufacture custom DNA molecules, such as Integrated DNA Technology, Twist Bioscience, and Atum. By ordering the right genes, which cost a few thousand dollars, and then stitching them together to create a copy of the coronavirus genome, its possible to inject the genetic material into cells and jump-start the virus to life.

The ability to make a lethal virus from mail-order DNA was first demonstrated 20 years ago. Its enough of a bioterrorism concern that companies carefully monitor who is ordering which genes. But its also an important way to respond to a sudden outbreak, since synthetic virus recipes give researchers powerful ways to study treatments, vaccines, and how mutations could make it more dangerous.

When a synthetic virus is better than the real thing

Barics North Carolina lab, which specializes in engineering viruses, has previously butted heads with Washington agencies over the work, which has included synthesizing new, never before seen coronaviruses that can infect mice. In 2014, the National Institutes of Health froze funding to several labs, including Barics, over concerns that such research was too risky. The funding was later reinstated.

For the China virus, Baric said in a telephone interview, his team placed an order for matching DNA from a manufacturer last month. Their first step was to go online and look at genetic sequences of the virus. They then compared several available sequences, which differ slightly, and picked a consensus version to have manufactured.

Once Baric gets his DNA, something that could take a month, he plans to inject the genetic instructions into cells. If things go as planned, the cells should begin making actual infectious viral particles.

CDC

By rolling their own germs, scientists can get hold of viruses even if they cant obtain them directly from a country, especially one thats in the grip of an epidemic. Baric says so far samples of the live virus from patients have not been made widely available from China. This is the future in terms of how the medical research community responds to a new threat, says Baric.

The real virus and the synthetic one should be basically identical. But with the synthetic one, we have a DNA copy that we can go back to over and over and over again, to make genetically identical viruses, says Timothy Sheahan, a researcher at UNC who works with Baric. Starting from these copies, scientists can remove genes, add others, and figure out things like what makes the germ spread and how it gains access to human cells. Sheahan wants to try infecting mice with the virus and giving them various drugs to see what stops it.

Artificial copies may also help scientists keep up with the outbreaks unpredictable path. I worry this virus is going to mutate in the course of the epidemic, and this would allow me to study what effects those mutations have, says Stanley Perlman, a microbiologist who works on coronaviruses at the University of Iowa. The synthetic virus is just a substitute for the actual virus, but with the DNA clone you can manipulate it and find the weak points and develop a therapy.

During past outbreaks, scientists would have had to wait months or years to get a look at the germ behind an outbreak. But with SARS-CoV-2 it took only weeks until its genetic sequence was posted online. Immediately, some scientists began analyzing the genetic data, comparing it to viruses from bats, snakes and pangolins; they concluded it could have begun circulating last November.

Biotech companies, governments, and universities also quickly started ordering physical copies of particular genes found in the virus. DNA manufacturers say they have been deluged with orders for virus parts, including those useful for verifying diagnostic tests and others needed to make potential vaccines.

Its been a pretty dramatic uptick, starting with the publication of the genome, says Adam Clore, technical director of synthetic biology at IDT, based in Iowa, and one of the worlds largest sellers of DNA. Its high priority. There are a number of institutions that are devoting nearly all their energy working on detection or vaccines.

Still, most researchers need only one or two genes from the virus to carry forward work on tests and vaccines. Barics lab in North Carolina is the only one in the US known to be trying to re-create the virus completely from ordered DNA parts.

How to keep deadly viruses out of the wrong hands

It was in the early 2000s that scientists first showed that synthetic DNA strands could be used to resurrect viruses just from their genetic code. A team in New York State did it with polio, producing infectious material from DNA they ordered online.

The technology immediately created bio-weapon worries. What if terrorists used the technique to resurrect smallpox? That hasnt happened, but it does mean that scourges like polio, smallpoxand now the Chinese coronaviruscannot now ever be truly wiped out. Researchers at the US Centers for Disease Control and Prevention (CDC) drove that point home in 2005 when they resurrected the influenza virus that killed tens of millions in 1918-1919.

To keep the technology out of the hands of evil-doers, companies that manufacture DNA banded together a few years ago to limit access to dangerous genes. The big US players have all agreed to compare incoming DNA orders to a database of about 60 lethal germs and toxins called select agents so that only authorized labs can ever obtain the DNA needed to resurrect them.

CDC

At our request, Battelle, a scientific R&D company whose software ThreatSEQ can make those comparisons, ran the scenario of someone trying to order a copy of SARS-CoV-2. According to Craig Bartling, a senior research scientist at Battelle, the software flagged both the entire virus, and most of its genes individually, at the highest threat level. Bartling says the alerts went off because the virus is highly similar to the original SARS, a related virus that sparked a global outbreak starting in 2002.

Research into the new virus is seen as risky enough that manufacturers of DNA hurried last week to meet and formulate a policy about who should be able buy complete versions of the new germs genome. In a statement released on February 11, the International Gene Synthesis Consortium, a trade group, struck a cautious position. It said it would treat the new Chinese virus as if it were SARS, a germ added to the select agent list in 2012 and whose possession is tightly monitored by the US government.

That means anyone who wants a complete synthetic copy of SARS-CoV-2 would need to undergo specific and detailed vetting and prove they are already registered by the CDC to work with SARS, as the North Carolina researchers are.

However, companies that manufacture DNA still have discretion over what they sell and to whom, and not all of them think they should make the whole genome of this virus. Claes Gustaffson, founder and chief commercial officer of Atum, a DNA supplier in California, says hes gotten orders from eight companies for parts of the virus genome and has personally approved a request by a US government agency to make 90% of its geneslikely to create an attenuated (i.e., harmless) version of it.

They probably want to figure out how to make a vaccine as quickly as possible, says Gustaffson. But if someone wanted the whole thing, I wouldnt make it. Some things, like polio, you dont want to make, no matter who is asking.

UNC Gillings School of Public Health

Not everyone thinks synthesizing the new coronavirus is particularly dangerous. I dont really see a huge amount of risk, says Nicholas G. Evans, who studies biothreats at the University of Massachusetts, Lowell. Right now, a lot of people are spending a lot of time on how this coronavirus works. I think the risks are outweighed by the benefits.

The outbreak, which appears to have begun in a live animal market in the city of Wuhan, had caused more than 64,000 cases and 1,350 deaths in China by February 14, so its even worse than SARS, which killed 774 people.

Still, the US has not yet declared the new virus to be a select agent. According to Baric, the decision to add a new virus to the most-dangerous list is not made in the expanding outbreak, because it slows down research.

Scaring people

For now, only a very few sophisticated centers can actually re-boot a virus; theres no chance a nut working from a garage could do it. We are at the point where the best of the best can start to synthesize this new virus contemporaneously with the outbreak. But that is just a few labs, says Evans. Fortunately, we are still far from the point when lots of people can synthesize anything.

The advanced state of synthetic virus research, and the ability to genetically engineer germs, inevitably feeds fears, and conspiracy theories. Social media and some blog sites have been full of groundless speculation that the new virus was accidentally released from a Chinese bioweapon lab located outside of Wuhan. Theres no evidence that is the case, and substantial evidence it is not, but the rumor caused a diplomatic breach with China after it was repeated in the US Congress by a senator, Tom Cotton of Arkansas.

Baric says he doesnt see a particular danger to synthesizing the new virus at this stage of the outbreak, especially because the virus is still circulating in the wild. The important thing is to figure out what it does and stop it. Whether you get it from a cell or synthesize it, it ends up the same thing, says Baric.

Read the original here:
Biologists rush to re-create the China coronavirus from its DNA code - MIT Technology Review

The Insight Partners recently added Genetic Engineering market Report by manufacturers, regions, type and application, forecast to 2027 in his database. This research report focus on complete assessment of market and contains future trend, growth factors, attentive opinions, facts, historical data, statistically supported and industry validated market data. Environmental concerns & regulatory guidelines regarding release of effluents through different industries. Genetic Engineering market comprehensive coverage of underlying economic and technological factors under key trend analysis.

If your Company involved in the Genetic Engineering industry or intend to be, then this study will provide you comprehensive outlook Future Industry by Analysts and know what to expect from this along with analysis By Industry Experts. Its vital you keep your market knowledge up to date segmented by In-Depth Insight of Sales Analysis, Growth Forecast and Upcoming Trends Opportunities by Applications Manufacturing, Product Types By major Manufacturers. If you have a different set of players/manufacturers according to geography or needs regional or country segmented reports we can provide customization according to your requirement globally With Expanding Future Business Scope.

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MARKET INTRODUCTION

A gene is the basic physical and function unity of heredity. Genetic engineering is the changing the structure of the genes of a living things in order to make it healthier, stronger and more useful to human. Changing DNA in cell is to understand their biology. Genetic engineering are currently used in both animal and plant cells this modifications are helps to improve performance of cell.

MARKET DYNAMICS

The genetic engineering market is expected to grow during the forecast period due to rising use of genetic engineering in the field of medical as well as in agriculture, high prevalence of infectious disease and awareness of steam cell therapy, and increasing no of genomics project due to government raising funds in genetic engineering field and more R&D. Thus, various governments are taking initiatives to create awareness amongst people about genetic engineering.

The report also includes the profiles of key Genetic Engineering Market companies along with their SWOT analysis and market strategies. In addition, the report focuses on leading industry players with information such as company profiles, components and services offered, financial information of last 3 years, key development in past five years.

Key Competitors In Market are

Integrated DNA Technologies, Thermo Fisher Scientific, Merck KGaA, Horizon Discovery Group, Transposagen Biopharmaceuticals, New England Biolabs, Genscript Biotech Corporation, Lonza Group, Origene Technologies, Sangamo Therapeutics

TOC pointsof Market Report:

Market size & shares

Market trends and dynamics

Market Drivers and Opportunities

Competitive landscape

Supply and demand

Technological inventions in industry

Marketing Channel Development Trend

Market Positioning

Pricing Strategy

Brand Strategy

Target Client

MARKET SCOPE

The Global Genetic Engineering Market Analysis to 2027 is a specialized and in-depth study with a special focus on the global market trend analysis. The report aims to provide an overview of Genetic Engineering Market with detailed market segmentation by product type, drug class, and geography. The global genetic engineering market is expected to witness high growth during the forecast period. The report provides key statistics on the market status of the leading genetic engineering market players and offers key trends and opportunities in the market.

Market segmentation:

Genetic Engineering Market to 2027 Global Analysis and Forecasts by Technology (CRISPR, TALEN, ZFN, Antisense, Other Technologies); By Application (Cell line Engineering, Genetic Engineering, Diagnostics & Therapeutics); By End User (Pharmaceutical and Biotechnology Companies, Academic and Research Institutes, Contract Research Organizations) and Geography

By Geography North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA) and South & Central America. And 13 countries globally along with current trend and opportunities prevailing in the region.

The target audience for the report on the market

Manufactures

Market analysts

Senior executives

Business development managers

Technologists

R&D staff

Distributors

Investors

Governments

Equity research firms

Consultants

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Read more from the original source:
Genetic Engineering Market to Reflect Impressive Expansion by Integrated DNA Technologies, Thermo Fisher Scientific, Merck KGaA, Horizon Discovery...

The power of speculative fiction often lies in its ability to make us look at the world around us with fresh eyes. Mundane acts have a way of becoming extraordinarily beautiful when we are faced with the prospect of their vanishing. Here, baseball becomes a site of resistance, an emblem of humanity, an antidote to the automation and artificial intelligence that controls every other aspect of life in AutoAmerica. After all, what would be the point of automating such a thing as nine human players throwing and catching balls to the best of their physical abilities? What significance could there possibly be in a robot pitching a perfect game? We are here, one coach says late in the novel, because we believe anything can happen in a ballgame. You can get a guy and all his stats but give him a stick to swing, and you still dont know what will happen. Its a marvelously refreshing concept in a world that is otherwise dominated by algorithms.

The Resisters is a book that grows directly out of the soil of our current political moment, and much of the books unsettling pleasure lies in Jens ingenious extrapolation (or, in some cases, redescription) of contemporary problems. The book brims with EnforceBots (police robots), ThoughtCommand (next-level voice command), PermaDerms (permanent skin whitening) and SmartGuns. AutoAmerica is a nation shaped by policies like ShipEmBack, a mass deportation of immigrants, and the One Chance Policy, wherein Surplus families are permitted only one pregnancy, no matter the outcome.

Jen has such a gifted ear for the manipulative languages of tech, marketing and government that at times the sheer abundance of clever details threatens to overwhelm the stories of her characters. But perhaps this overabundance is part of the novels method, a way of swallowing the characters and the reader into AutoAmericas reality. The Resisters is aimed at many catastrophes at once: surveillance technology, government overreach, authoritarianism, automation, economic inequality, racism, sexual assault and the institutional mishandling of it, geopolitical conflict and climate change.

The central thread of the book, though, or perhaps the most lingering, is its obsession with the threats of artificial intelligence. The Resisters is full of characters who voluntarily hand over their humanity by agreeing to GenetImprovement or by mindlessly following the orders of Aunt Nettie. In one unnerving section, the narrator recounts the incremental steps that led to this all-encompassing control first, he let Aunt Nettie keep his calendar, then respond to emails on his behalf. (The Resisters might make you stop and actually read your user agreements.)

In the most devastating moment of this ultimately quite tender novel, one characters mind is surgically merged against her will with Aunt Nettie, so that the line between human and internet is no longer clear, even to herself. Crucially, it is other human beings who carry out this dreadful procedure, which suggests that even in a dystopian world dominated by artificial intelligence, people are still the ones who carry out the most atrocious acts.

We live in a moment when The Handmaids Tale is a hit television show, and Kellyanne Conways use of the term alternative facts reminded so many readers of the double talk in George Orwells classic 1984 that the novel hit the best-seller list seven decades after its original publication. The public seems to feel that the worst speculative fictions are coming true. Of course, Margaret Atwood would contend that The Handmaids Tale was true even as it was written. Perhaps Gish Jen could make a similar argument about much of The Resisters. The hope she offers, though, lies in the books title, and in the heroism of its family of Bartlebys, who resist both the lure of conveniences and the threats of the powerful, with one phrase: I would prefer not to.

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The Future Is Here, and Uncomfortably Close to Home - The New York Times

Type 2 diabetes is a condition that means insulin in the pancreas doesnt work properly. Everybody needs insulin to live and has an essential job to help keep the body healthy. Insulin allows the glucose in the blood to enter the cells and fuel the body. When a person suffers from type 2 diabetes, the impact could create a myriad of health problems. But what are the biggest symptoms to look out for when it comes to type 2 diabetes?

New research by Simplyhealth, which Dr Dawn is the ambassador of, revealed when it comes to staying healthy, only 16 percent focus on visiting the doctor when they feel unwell, while the average Briton waiting over two weeks before booking an appointment with their doctor about a minor health concerns.

This appears to be taking its toll, with one in five admitting their illnesses last longer as they cant get to the doctors due to other commitments.

For type 2 diabetes, ignoring symptoms could have a disastrous effect on ones health.

READ MORE: High blood pressure signs: The worrying symptom in your eyes that could signal your risk

Dr Harper told Express.co.uk: The biggest problems we have with type 2 diabetes is that there are literally tens of thousands of people walking around out there today with established type 2 diabetes who have no idea because they dont have symptoms.

We know that by the time an individual is diagnosed with type 2 diabetes they have about a 50 percent chance of already have started to develop some of the complications which may not have been manifested themselves but they are very serious complications with things like eye disease, kidney disease, high blood pressure, the risk of heart disease and stroke."

DONT MISS

The important issue that we have is that a lot of people wouldnt necessarily know they have type 2 diabetes," continued Dr Harper.

"One of the reasons why we are so keen that people attend things like the NHS health check to get tested because you may have no symptoms whatsoever."

When asked who is most at risk of developing type 2 diabetes, Dr Dawn replied: I think if you are a person who is putting on weight especially around your midriff then that could be a sign that you could be at risk and you need to get tested.

The NHS said: Type 2 diabetes is a common condition that causes the level of sugar in the blood to become too high.

"It can cause symptoms like excessive thirst, needing to pee a lot and tiredness.

"It can also increase your risk of getting serious problems with your eyes, heart and nerves.

"Its a lifelong condition that can affect your everyday life. You may need to change your diet, take medicines and have regular checkups. Its caused by problems with a chemical in the body called insulin.

"Its often linked to being overweight or inactive, or having a family history of type 2 diabetes.

See original here:
Type 2 diabetes warning: Dr Dawn Harper says those with condition 'may have no symptoms' - Express

A link has been found between women who have high levels of testosterone and an increased risk of type 2 diabetes, metabolic disease and cancer.

Although testosterone supplements are commonly used to treat sexual function, bone health and body composition, it is largely unknown what the long terms effects on disease risk and outcomes is. Researchers from Exeter University set out to see if there is any evidence for long term effects associated with high testosterone levels.

In their study, which involved around 425,000 people, has found evidence that females who have raised levels of the sex hormone have a 37 per cent higher risk of being diagnosed with type 2 diabetes.

Interestingly, the study revealed that for males with genetically high levels of testosterone, the risk of developing type 2 diabetes is 14 per cent lower. Although, findings suggested there was an increased chance of prostate cancer among males with high testosterone levels.

Although testosterone is usually associated with men, being the male sex hormone, women also produce small amounts of it in the ovaries and adrenal glands. This study looked at females who were genetically prone to greater testosterone levels and found, not only a higher type 2 diabetes risk, but also a 51 per cent increased risk of developing polycystic ovary syndrome a hormonal disorder that affects menstruation.

Genetics specialist Dr Katherine Ruth from Exeter University, who co-lead the study, said their findings have helped to emphasise the importance of considering men and women separately in studies, as we saw opposite effects for testosterone on diabetes.

Dr John Perry, who also worked on the trial and is from Cambridge University, added: In men, testosterone-reducing therapies are widely used to treat prostate cancer, but until now it was uncertain whether lower testosterone levels are also protective against developing prostate cancer.

The research has been published in the journal Nature Medicine.

Visit link:
High levels of testosterone linked to greater risk of type 2 diabetes in women - Diabetes.co.uk

Over the last two decades, few drugs have been approved for the treatment of AML, however increased understanding of the leukemic genome has allowed the development of targeted therapeutic agents.2,3 Between April 2017 and November 2018, eight new drugs in various different classes were approved, including: enasidenib, ivosidenib, midostaurin, glasdegib, venetoclax, and gilteritinib.4 An overview of mutations that can be targeted in AML is available on the AML Global Portal (AGP).

Some of these targeted agents are being investigated in novel combination therapies, as different lines of AML treatment, and some as monotherapy compared to standard chemotherapy. This article provides a summary of AGP content relating to novel agent-containing combinations to date and introduces the new editorial theme of Novel combination therapies using targeted agents.

The AGP were pleased to speak to Andrew Wei during the European School of Haematology (ESH) Translational Research Conference on AML, 2019, about how targeted therapies will be used in the future treatment of AML. In this interview, available below, Andrew Wei discusses whether these targeted agents should be used in combination or sequentially.

During the American Society of Clinical Oncology (ASCO) meeting in 2018, the AGP spoke to Uma Borate about how targeted therapies will impact the treatment of AML. Uma Borate discussed targeted agents, such as venetoclax, azacitidine, ivosidenib, and enasidenib.

Precision medicine may have a particular role in the treatment of older patients, since this population are often unable to receive allo-HSCT or intensive chemotherapy regimens. During the 61st American Society of Hematology (ASH) meeting, the AGP spoke to John Byrd about how precision medicine may be used to improve the outcomes of older patients with AML.

The AGP interviewed Courtney DiNardo about the treatment of elderly or frail patients with AML at the 1st National Cancer Research Institute (NCRI) AML Academy Meeting. Watch Courtney DiNardo discuss how the treatment approach for this patient group has changed in recent years with the advent of combination therapies below.

Studies have shown that epigenetic dysregulation can promote a preleukemic state that precedes leukemic transformation. Drugs targeting epigenetic dysregulation have been developed and include: azacitidine and decitabine, which are hypothesized to reverse DNA hypermethylation and reactivate repressed tumor suppressor genes; ivosidenib and enasidenib, which target IDH1 and IDH2 mutations thought to be involved in aberrant DNA hypermethylation.2 Combining these agents may improve patient outcome compared to azacitidine monotherapy.

Ivosidenib/enasidenib plus azacitidine: phase I/II study: AG221-AML-005 (NCT02677922)5,6,7

Patients with newly diagnosed AML, with either IDH1 mutations (mIDH1) or IDH2 mutations (mIDH2), were treated with azacitidine plus ivosidenib (for mIDH1) or enasidenib (for mIDH2).

Ivosidenib/enasidenib plus standard chemotherapy8

A phase III study, HOVON 150/AMLSG 29-18, is comparing enasidenib or ivosidenib (by mIDH status) plus chemotherapy (7+3) versus placebo.9 An overview of IDH inhibitors, including further information on the data from trials involving these combination therapies, is available here.

Other new targets for AML therapies are the FLT3 pathways. FLT3 is a transmembrane tyrosine kinase with two mutational subtypes: an internal tandem duplication (ITD) or point mutations in the tyrosine kinase domain (TKD).4 A third of patients with de novo AML have mutations in the FLT3 gene and patients with FLT3-ITD AML have a poor prognosis. FLT3 is therefore an attractive target for therapeutic agents, with several FLT3 inhibitors in clinical development, such as sorafenib, midostaurin, quizartinib, crenolanib, and gilteritinib.2,4

Examples of combination therapies involving FLT3 inhibitors are shown in Table 1 below. One example of a trial involving a FLT3 inhibitor is the RATIFY (NCT00651261) trial. The RATIFY trial assessed whether the addition of midostaurin to standard chemotherapy could prolong survival in newly diagnosed adult patients with FLT3-ITD AML compared to placebo + chemotherapy. The results showed midostaurin prolonged median OS and event-free survival (EFS) compared to placebo10:

However, the authors questioned if more specific FLT3 inhibitors could further improve outcomes.10

Table 1. Examples of combination therapies containing FLT3 inhibitors4,11,12

Targeted agent

In combination with/versus

Patient population

Trial name/NCT reference

Midostaurin

Induction chemo

ND AML with FLT3-ITD or TKD mutations

RATIFY

NCT00651261

Quizartinib

Induction chemo

ND AML with FLT3-ITD mutations

QuANTUM-First

NCT02668653

Crenolanib

vs midostaurin, in combination with induction chemo

ND AML with FLT3-ITD mutations

NCT03258931

Gilteritinib

Induction chemo

ND AML

NCT02310321

Sorafenib

Induction chemo

ND AML <60 years old

SORAML

NCT00893373

Learn more about FLT3 inhibitors in AML here.

During the 2019 EHA meeting, the AGP spoke to Alexander Perl about gilteritinib for the treatment of relapsed/refractory (R/R) AML.

Another example of a targeted agent for the treatment of AML is venetoclax, which is a Bcl-2 inhibitor. Venetoclax is approved by the U.S. Food & Drug Administration (FDA) for the treatment of newly diagnosed patients with AML who are not eligible for intensive induction chemotherapy, in combination with azacitidine, decitabine, or low dose cytarabine.13

Results from a phase Ib study (NCT02203773) investigating venetoclax with decitabine or azacitidine showed that these combination therapies led to a 61% complete remission or complete remission with incomplete marrow recovery rate in newly diagnosed patients with AML aged 65 and over.14 A phase III study (NCT02993523) comparing venetoclax plus azacitidine to azacitidine alone in patients with treatment-nave AML is ongoing.15

During the Acute Leukemias XVII Biology and Treatment Strategies biennial symposium, Andrew Wei gave a presentation on novel therapeutic combinations containing venetoclax for the treatment of AML.

There are a number of ongoing studies of venetoclax in combination therapies and examples of these include4:

During the 2018 ASCO meeting, the AGP spoke to Courtney DiNardo about the combination of venetoclax with hypomethylating agents (HMAs).

Subsequently, during the Society of Hematologic Oncology (SOHO) meeting in 2019, the AGP spoke to Jeffrey Lancet about the potential of venetoclax + HMAs to replace induction chemotherapy.

The AGP spoke to Marina Konopleva at the 2019 EHA meeting about Bcl-2 as a universal target in AML.

The development of targeted therapies and novel combinations holds promise for the treatment of AML, especially when compared to currently approved options. In some cases, these combinations may be more efficacious than intensive induction chemotherapy. In addition, some patients have been able to undergo allo-HSCT following treatment with a novel combination, which may indicate that the future of AML treatment will be in novel combinations and involve less chemotherapy. Additionally, these combinations appear tolerable to date.

Despite the promising results seen so far, not all patients respond equally. In order to maximize response to these therapies, it will be important to identify the right patient subgroups, with specific mutations, and may require particular combinations of agents to be used.2

Read this article:
An introduction to novel combination therapies using targeted agents in AML - AML Global Portal

Meticulous Research leading global market research company published a research report titled Medical Aesthetics Market by Product (Facial Aesthetics, Cosmetic Implants, Skin Aesthetic Devices, Thread Lift Products, Body Contouring Devices, Hair Removal Devices), End User (Hospitals, Medical Spas, Home Care Settings)Global Forecast to 2025.

According to this latest publication from Meticulous Research, the global medical aesthetics market is expected to grow at a CAGR of 11.5% from 2019 to reach $22.2 billion by 2025. The growth of this market will be driven by factors such as increasing adoption of minimally invasive and noninvasive aesthetic procedures, increasing public awareness about cosmetic procedures, and rising adoption of medical aesthetic procedures among geriatric population to improve their appearance. However, risk and complications associated with medical aesthetic procedures may hamper the growth of the market to a certain extent.

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Key questions answered in the report-Which are the high growth market segments in terms of products, technology, disease type, end user, and region/countries?What was the historical market for medical aesthetics market across the globe?What are the market forecasts and estimates for the period 2018-2025?What are the major drivers, opportunities, and challenges in the global medical aesthetics market?Who are the major players in the global medical aesthetics market?How is the competitive landscape and who are the market leaders in the global medical aesthetics market?What are the recent developments in the global medical aestheticsmarket?What are the different strategies adopted by the major players in the global medical aesthetics market?What are the geographical trends and high growth regions/ countries?Who are the local emerging players in the global medical aesthetics market and how do they compete with the global players?

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The global medical aesthetics market study presents historical market data in terms of values (2017 and 2018), estimated current data (2019), and forecasts for 2025- by product (facial aesthetics, cosmetic implants, skin aesthetic devices, physician-dispensed cosmeceuticals and skin lighteners, thread lift products, body contouring devices, hair removal devices, tattoo removal devices, and nail treatment laser devices), and end user (hospitals, clinics, and medical spas, beauty centers, and home care settings). The study also evaluates industry competitors and analyzes the market at a regional and country level.

On the basis of product type, facial aesthetics market segment is estimated to command the largest share of the global medical aesthetics market in 2019; whereas, cosmetic implants segment is expected to grow at the highest CAGR during the forecast period due to increasing growth of minimally invasive reconstruction surgeries, technological advancements such as injectable fillers and gummy bear breast implants, rising number of congenital face disorders, and increasing awareness about aesthetic appearance. A comprehensive range of cosmetic plastic surgery techniques and implants have been developed over the years for improving the appearance or restoring function to the human body. The implants used in cosmetic procedures are to enhance the aesthetic looks of an individual and rectify the deformities caused due to accidents, trauma, and congenital disorders.

On the basis of end user, hospitals, clinics, and medical spas segment is estimated to hold the largest share of the global medical aesthetics market in 2019. Hospitals, clinics, and medical spas are typically well-equipped with technologically advanced instruments/devices and have skilled professionals to provide effective cosmetic treatment to its patients. This has led to their greater share in the global medical aesthetics market. Hospital and medical spas design their services to improve the aesthetic procedures for patient well-being. Medical aesthetic services involve highly advanced technology that needs the combination of healthcare and beauty services. In aesthetic treatment, advanced technologies are increasingly being used to provide medical procedures designed to offer significant cosmetic change for patients. The growth of the hospitals, clinics, and medical spas segment in the market is primarily driven by the growing number of patients undergoing cosmetic procedures to enhance self-esteem, increasing healthcare expenditure on cosmetic procedures, growing geriatric population, and greater uptake of technologically advanced medical aesthetics devices in the hospitals and clinics to provide effective treatments to the patients.

Browse key industry insights spread across 195 pages with 185 market data tables & 18 figures & charts from the market research report:https://www.meticulousresearch.com/product/medical-aesthetics-market-5028/

Geograhic Review:

This research report analyzes major geographies and provides comprehensive analysis of North America (U.S., Canada), Europe (Germany, France, Italy, Spain, and U.K.), Asia-Pacific (China, India, South Korea, Japan, and Australia), Latin America, and Middle East & Africa. North America commanded the largest share of the global medical aesthetics market, followed by Europe and Asia Pacific. The largest share of North American region in the medical aesthetics market is primarily attributed to the growing healthcare sector, increasing awareness and adoption of aesthetic procedures among the population, growing healthcare expenditure, rising incidences of skin diseases, growing geriatric population, various technological advancements, and increase in the consciousness about physical appearances.

Asia Pacific region is expected to be the fastest growing geographic markets for medical aesthetics devices with countries, such as China, Japan, South Korea and India among others for being the largest contributors to the growth of the market. Additionally, rapid urbanization, increasing investments by healthcare providers towards infrastructure improvement, increasing awareness among the population, growing beauty consciousness, and availability of increasing range of advanced products and technologies is contributing to the growth of the medical aesthetics market in the Asia Pacific region.

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Key players:

The major players operating in the globalmedical aesthetics marketare Allergan plc (Ireland), Alma Lasers (Israel), Anika Therapeutics, Inc. (US), Cutera, Inc. (US), Cynosure Inc. (US), El.En. S.P.A. (Italy), Fotona D.O.O (Solvenia& US), Galderma Laboratories, L.P. (US), Mentor Worldwide LLC (US), and Merz Aesthetics (Germany) among others.

Related Report:

Surgical Sutures Market by Product (Suture Thread (Synthetic, Nylon, Silk, Prolene, Steel), Automatic Suture Device), Application (CVD, General, Orthopedic, Gynec, Ophthalmic, Plastic, Cosmetics), End User (Hospitals, ASC, Clinic) Global Forecast to 2024

Flow Cytometry Market by Product (Cell Analyzers, Cell Sorter, Software, Reagents), Technology (Cell Based, Bead Based), Application (Drug Discovery, Stem Cell Research, Cancer, Organ Transplant, Commercial) and by End-user Global Forecast to 2027

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Medical Aesthetics Market Is Expected To Grow At CAGR Of 11.5% From 2019 To Reach $22.2 Billion By 2 - PharmiWeb.com

DetailsCategory: Small MoleculesPublished on Wednesday, 12 February 2020 17:52Hits: 446

PLEASANTON, CA, USA I February 11, 2020 I Astex Pharmaceuticals, Inc., a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Japan, today announced that the U.S. FDA has accepted for Priority Review its NDA for oral C-DEC (cedazuridine and decitabine) as a treatment for adults with previously untreated intermediate- and high-risk MDS including CMML. The NDA submission is based on data from the ASCERTAIN phase 3 study which evaluated the 5-day decitabine exposure equivalence of oral C-DEC and IV decitabine.

We are very pleased that the FDA has accepted our NDA for Priority Review, said Dr Mohammad Azab, MD, president & chief medical officer of Astex Pharmaceuticals, Inc. Subject to FDA review and regulatory approval, oral C-DEC may offer a new option for patients with MDS and CMML that saves them the burden of 5-day IV infusions every month during their treatment period. We are grateful to all the patients, investigators and other healthcare providers, and partner research and manufacturing organizations, who contributed to the clinical development program of oral C-DEC.

The FDA grants Priority Review to applications for drugs that, if approved, would provide significant improvements in the safety and effectiveness of the treatment, diagnosis or prevention of serious conditions. The Priority Review designation means FDAs goal is to take action on an NDA application within six months (compared to the ten months under standard review).

Oral C-DEC is an investigational compound and is not currently approved in any country.

Astexs parent company, Otsuka Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd. previously announced that, subject to regulatory approvals, commercialization of oral C-DEC in the U.S. and Canada will be conducted by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc. respectively. Astex, Otsuka and Taiho are all members of the Otsuka group of companies.

About C-DEC (Cedazuridine 100 mg and Decitabine 35 mg) Fixed-Dose Combination

C-DEC is a novel, orally administered fixed dose combination of cedazuridine, an inhibitor of cytidine deaminase,1 with the anti-cancer DNA hypomethylating agent, decitabine.2 By inhibiting cytidine deaminase in the gut and the liver, C-DEC is designed to allow for oral delivery of the approved DNA hypomethylating agent, decitabine, at exposures which emulate exposures achieved with the approved intravenous form of decitabine administered over 5 days.3

C-DEC has been evaluated in a phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study in patients with MDS and CMML (see https://www.clinicaltrials.gov NCT02103478) and a pivotal phase 3 study (ASCERTAIN) (see https://www.clinicaltrials.gov NCT03306264) conducted at investigator sites in the US and Canada and designed to confirm the results from the phase 1/2 study. The phase 3 study is now being extended to include patients with acute myeloid leukemia (AML) unsuitable to receive intensive induction chemotherapy.

In September 2019 Astex announced that C-DEC had received orphan drug designation for the treatment of MDS and CMML from the U.S. FDA.

The concept of using cedazuridine to block the action of cytidine deaminase is also being evaluated in a low dose formulation of cedazuridine and decitabine for the treatment of lower risk MDS (see https://www.clinicaltrials.gov NCT03502668).

About the Phase 3 ASCERTAIN Study

The study was designed as a randomized crossover study comparing oral C-DEC (cedazuridine 100 mg and decitabine 35 mg fixed-dose combination tablet given once daily for 5 days on a 28-day cycle) to IV decitabine (20 mg/m2 administered as a daily, 1-hour IV infusion for 5 days on a 28-day cycle) in the first 2 cycles with patients continuing to receive oral C-DEC from Cycle 3 onwards. The data from the ASCERTAIN study was presented at the American Society of Hematology (ASH) Meeting in Orlando, Florida in December 2019 by Dr Guillermo Garcia-Manero, MD, professor and chief of section of myelodysplastic syndromes, Department of Leukemia at The University of Texas MD Anderson Cancer Center, on behalf of the study investigators.4 The data demonstrated that the ASCERTAIN study met the primary endpoint of total 5-Day decitabine Area-Under-The-Curve (AUC) equivalence of oral C-DEC and IV decitabine. Safety findings from the study were consistent with those anticipated with IV decitabine, with no significant differences in the incidence of most common adverse events between oral C-DEC and IV decitabine in the first 2 randomized cycles. The most common adverse events of any grade >20% regardless of causality in patients in the first 2 randomized cycles who received oral C-DEC were thrombocytopenia (43.8%), neutropenia (35.4%), anemia (36.9%), and fatigue (23.8%). The ASH presentation can be downloaded from the Astex website at https://astx.com/media-center/presentations-and-publications/ASTX727 ASCERTAIN Presentation - ASH - December 2019

About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. U.S. incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.5,6 The prevalence has been estimated to be from 60,000 to 170,000 in the U.S.7 MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.8 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML. CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the U.S. is approximately 1,100 new cases per year,9 and CMML may transform into AML in 15% to 30% of patients.10 The hypomethylating agents decitabine and azacitidine are effective treatment modalities for hematologic cancers and are FDA-approved for the treatment of higher-risk MDS and CMML. These agents are administered by IV infusion, or by large-volume subcutaneous injections.

About Astex Pharmaceuticals, Inc.

Astex is a leader in innovative drug discovery and development, committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies and has multiple partnered products in development under collaborations with leading pharmaceutical companies. Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.

Otsuka is a global healthcare company with the corporate philosophy: Otsukapeople creating new products for better health worldwide. Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

For more information about Astex Pharmaceuticals, Inc. please visit: http://www.astx.com

For more information about Otsuka Pharmaceutical, please visit: http://www.otsuka.com/en/

For more information about Taiho Pharmaceutical, please visit: https://www.taihooncology.com/

References

SOURCE: Astex Pharmaceuticals

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KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the pivotal Phase 3 KEYNOTE-355 trial investigating KEYTRUDA, Mercks anti-PD-1 therapy, in combination with chemotherapy met one of its dual primary endpoints of progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (mTNBC) whose tumors expressed PD-L1 (Combined Positive Score [CPS] 10). Based on an interim analysis conducted by an independent Data Monitoring Committee (DMC), first-line treatment with KEYTRUDA in combination with chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) demonstrated a statistically significant and clinically meaningful improvement in PFS compared to chemotherapy alone in these patients. Based on the recommendation of the DMC, the trial will continue without changes to evaluate the other dual primary endpoint of overall survival (OS). The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified.

Triple-negative breast cancer is an aggressive malignancy. It is very encouraging that KEYTRUDA in combination with chemotherapy has now demonstrated positive results as both a first-line treatment in the metastatic setting with this trial, and as neoadjuvant therapy in the KEYNOTE-522 trial, said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. We look forward to sharing these findings with the medical community at an upcoming congress and discussing them with the FDA and other regulatory authorities.

The KEYTRUDA breast cancer clinical development program encompasses several internal and external collaborative studies. In addition to KEYNOTE-355, in TNBC these include the ongoing registration-enabling studies KEYNOTE-242 and KEYNOTE-522.

About KEYNOTE-355

KEYNOTE-355 is a randomized, two-part, Phase 3 trial (ClinicalTrials.gov, NCT02819518) evaluating KEYTRUDA in combination with one of three different chemotherapies (investigators choice of either nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) compared with placebo plus one of the three chemotherapy regimens for the treatment of locally recurrent inoperable or mTNBC that has not been previously treated with chemotherapy in the metastatic setting. Part 1 of the study was open-label and evaluated the safety and tolerability of KEYTRUDA in combination with either nab-paclitaxel, paclitaxel or gemcitabine/carboplatin in 30 patients. Part 2 of KEYNOTE-355 was double-blinded, with dual primary endpoints of OS and PFS in all participants and in participants whose tumors expressed PD-L1 (CPS 1 and CPS 10). The secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and safety.

Part 2 of KEYNOTE-355 enrolled 847 patients who were randomized to receive KEYTRUDA (200 mg intravenously [IV] on day 1 of each 21-day cycle) plus nab-paclitaxel (100 mg/m2 IV on days 1, 8 and 15 of each 28-day cycle), paclitaxel (90 mg/m2 IV on days 1, 8 and 15 of each 28-day cycle) or gemcitabine/carboplatin (1,000 mg/m2 [gemcitabine] and Area Under the Curve [AUC] 2 [carboplatin] on days 1 and 8 of each 21-day cycle); or placebo (normal saline on day 1 of each 21-day cycle) plus nab-paclitaxel (100 mg/m2 IV on days 1, 8 and 15 of each 28-day cycle), paclitaxel (90 mg/m2 IV on days 1, 8 and 15 of each 28-day cycle) or gemcitabine/carboplatin (1,000 mg/m2 [gemcitabine] and AUC 2 [carboplatin] on days 1 and 8 of each 21-day cycle).

About Triple-Negative Breast Cancer (TNBC)

TNBC is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. As a result, TNBC does not respond to therapies targeting these markers, making it more difficult to treat. Approximately 15-20% of patients with breast cancer are diagnosed with TNBC.

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 1,000 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.

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).

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%).

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Original post:
Merck's KEYTRUDA (pembrolizumab) in Combination with Chemotherapy Met Primary Endpoint of Progression-Free Survival (PFS) as First-Line Treatment for...

BOTHELL, Wash. and TOKYO, Feb. 10, 2020 /PRNewswire/ --Seattle Genetics, Inc.(Nasdaq: SGEN) and Astellas Pharma Inc.(TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced updated results from the phase 1b/2 clinical trial EV-103 in previously untreated patients with locally advanced or metastatic urothelial cancer who were ineligible for treatment with cisplatin-based chemotherapy. Forty-five patients were treated with the combination of PADCEV (enfortumab vedotin-ejfv) and pembrolizumab and were evaluated for safety and efficacy. After a median follow-up of 11.5 months, the study results continue to meet outcome measures for safety and demonstrate encouraging clinical activity for this platinum-free combination in a first-line setting. Updated results will be presented during an oral session on Friday, February 14 at the 2020 Genitourinary Cancers Symposium in San Francisco (Abstract #441). Initial results from the study were presented at the European Society of Medical Oncology Congress in September 2019.

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.1,2

"Cisplatin-basedchemotherapy is the standard treatment for first-line advanced urothelial cancer; however, it isn't an option for many patients,"said Jonathan E. Rosenberg, M.D., Medical Oncologist and Chief, Genitourinary Medical Oncology Service at Memorial Sloan Kettering Cancer Center in New York."I'm encouraged by these interim results, including a median progression-free survival of a year for patients who received the platinum-free combination of PADCEV and pembrolizumab in the first-line setting."

In the study, 58 percent (26/45) of patients had a treatment-related adverse event greater than or equal to Grade 3: increase in lipase (18 percent; 8/45), rash (13 percent; 6/45), hyperglycemia (13 percent; 6/45) and peripheral neuropathy (4 percent; 2/45); these rates were similar to those observed with PADCEV monotherapy.3Eighteen percent (8/45) of patients had treatment-related immune-mediated adverse events of clinical interest greater than or equal to Grade 3 that required the use of systemic steroids (arthralgia, dermatitis bullous, pneumonitis, lipase increased, rash erythematous, rash maculo-papular, tubulointerstitial nephritis, myasthenia gravis). None of the adverse events of clinical interest were Grade 5 events. Six patients (13 percent) discontinued treatment due to treatment-related adverse events, most commonly peripheral sensory neuropathy. As previously reported, there was one death deemed to be treatment-related by the investigator attributed to multiple organ dysfunction syndrome.

The data demonstrated the combination of PADCEV plus pembrolizumab shrank tumors in the majority of patients, resulting in a confirmed objective response rate (ORR) of 73.3 percent (33/45; 95% Confidence Interval (CI): 58.1, 85.4) after a median follow-up of 11.5 months (range,0.7 to 19.2). Responses included 15.6 percent (7/45) of patients who had a complete response (CR)and 57.8 percent (26/45) of patients who had a partial response. Median duration of response has not yet been reached (range 1.2 to 12.9+ months). Eighteen (55%) of 33 responses were ongoing at the time of analysis, with 83.9% of responses lasting at least 6 months and 53.7% of responses lasting at least 12 months (Kaplan-Meier estimate).The median progression-free survival was 12.3 months (95% CI: 7.98, -) and the 12-month overall survival (OS) rate was 81.6 percent (95% CI: 62 to 91.8 percent); median OS has not been reached.

"These updated data are encouraging and provide support for the recently initiated phase 3 trial EV-302 that includes an arm evaluating PADCEV in this platinum-free combination in the first-line setting," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.

"These additional results support continued evaluation of PADCEV in combination with other agents and at earlier stages of treatment for patients withurothelial cancer," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas.

About the EV-103 TrialEV-103 is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of PADCEV alone or in combination, evaluating safety, tolerability and efficacy in muscle invasive, locally advanced and first- and second-line metastatic urothelial cancer.

The dose-escalation cohort and expansion cohort A include locally advanced or metastatic urothelial cancer patients who are ineligible for cisplatin-based chemotherapy. Patients were dosed in a 21-day cycle, receiving an intravenous (IV) infusion of enfortumab vedotin on Days 1 and 8 and pembrolizumab on Day 1. At the time of this initial analysis, 45 patients (5 from the dose-escalation cohort and 40 from the dose-expansion cohort A) with locally advanced and/or metastatic urothelial cancer had been treated with enfortumab vedotin (1.25 mg/kg) plus pembrolizumab in the first-line setting.

The primary outcome measure of the cohorts included in this analysis is safety. Key secondary objectives related to efficacy include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression free survival (PFS) and overall survival (OS). DoR,PFS and OS are not yet mature.

Additional cohorts in the EV-103 study will evaluate enfortumab vedotin:

More information about PADCEV clinical trials can be found at clinicaltrials.gov.

About Bladder and Urothelial CancerIt is estimated that approximately 81,000 people in the U.S. will be diagnosed with bladder cancer in 2020.5 Urothelial cancer accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.6 Globally, approximately 549,000 people were diagnosed with bladder cancer in 2018, and there were approximately 200,000 deaths worldwide.7

The recommended first-line treatment for patients with advanced urothelial cancer is a cisplatin-based chemotherapy. For patients who are ineligible for cisplatin, such as people with kidney impairment, a carboplatin-based regimen is recommended. However, fewer than half of patients respond to carboplatin-based regimens and outcomes are typically poorer compared to cisplatin-based regimens.8

About PADCEV PADCEV (enfortumabvedotin-ejfv) was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.9

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.2,9Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).9PADCEV is co-developed by Astellas and Seattle Genetics.

Important Safety Information

Warnings and Precautions

Adverse ReactionsSerious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

The most common adverse reactions (20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade 3 adverse reactions (5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Lab AbnormalitiesIn one clinical trial, Grade 3-4 laboratory abnormalities reported in 5% were: lymphocytes decreased, hemoglobin decreased, phosphate decreased, lipase increased, sodium decreased, glucose increased, urate increased, neutrophils decreased.

Drug Interactions

Specific Populations

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

About Seattle GeneticsSeattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in people's lives. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland and the European Union. For more information on our robust pipeline, visit https://www.seattlegenetics.comand follow @SeattleGenetics on Twitter.

About AstellasAstellas Pharma Inc., based in Tokyo, Japan, is a company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. For more information, please visit our website at https://www.astellas.com/en.

About the Astellas and Seattle Genetics CollaborationSeattle Genetics and Astellas are co-developing enfortumab vedotin-ejfv under a collaboration that was entered into in 2007 and expanded in 2009. Under the collaboration, the companies are sharing costs and profits on a 50:50 basis worldwide.

Seattle Genetics Forward-Looking StatementsCertain statements made in this press release are forward looking, such as those, among others, relating to the EV-103 and EV-302 clinical trials; clinical development plans relating to enfortumab vedotin; the therapeutic potential of enfortumab vedotin; and its possible safety, efficacy, and therapeutic uses, including in the first-line setting. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that ongoing and subsequent clinical trials of enfortumab vedotin may fail to establish sufficient efficacy; that adverse events or safety signals may occur and that adverse regulatory actions or other setbacks could occur as enfortumab vedotin advances in clinical trials even after promising results in earlier clinical trials. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2019 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

Astellas Cautionary NotesIn this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

1 PADCEV [package insert]. Northbrook, IL: Astellas, Inc.2 Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.3 Rosenberg JE, O'Donnell PH, Balar AV, et al. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol 2019;37(29):2592-600.4 ClinicalTrials.gov. A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer (EV-103). https://clinicaltrials.gov/ct2/show/NCT03288545.5 American Cancer Society. Cancer Facts & Figures 2020. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed 01-23-2020.6National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed 05-01-2019.7International Agency for Research on Cancer. Cancer Tomorrow: Bladder. http://gco.iarc.fr/tomorrow. 8 National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. Version 4; July 10, 2019. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf.9 PADCEV [package insert]. Northbrook, IL: Astellas, Inc.

SOURCE Astellas

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Seattle Genetics and Astellas Announce Updated Results from Phase 1b/2 Trial of PADCEV (enfortumab vedotin-ejfv) in Combination with Immune Therapy...

Right now, Stanford University is addressing a pressing and fascinating question:

What happens to society when everyone starts living to 100? How will we stay physically fit, financially stable and mentally sharp, especially in that back half?

Exploring these questions is the goal of the Stanford Longevity Project. To answer them, theyve partnered with major brands like Wells Fargo, Instructure, and Principal to help research key elements like financial security, lifelong learning, and healthcare.

Despite Americas average life expectancy declining the past couple years due to more overdoses, suicides and alcohol-related illnesses, people are going to be able to live longer. Strong advancements have been made in cancer. This month, the U.S. saw its sharpest one year decline in cancer death rate. That will save millions of lives alone.

But this isnt just a health and wellness conversation. What this presents are multiple opportunities in multiple verticals for marketers.

One of the biggest trends at CES this month was a new generation of healthcare wearables. There were earbuds designed to detect blood pressure for those with hypertension, temporary tattoos that tell you when to get out of the sun, smart glasses that assist people with dyslexia and watches that detect sleep apnea. These technologies are all discreet, easy to use, and built in to everyday things we already use.

We are heading toward a near future in which every human body will have a functioning check engine light. You can imagine how much better healthcare will be when a sensor will tell you something needs attention, rather than panicked scrolling through WebMD.

We will have the ability to know when something is wrong and immediately trigger tests, medication and treatment. Imagine if that sensor, using the IoT, could immediately send and fill a prescription for you.

This is all coming down the pipeline, and its going to help us live longer. Its also going to change the way marketers do their jobs and open up countless new opportunities to reach new audiences.

Heres what some of those opportunities will look like.

Cincinnati has one of the best healthcare startup scenes in the country. Cincinnati Childrens Hospital is ranked #3 nationally. CincyTech has raised nearly a billion in healthcare follow-on investment over the past ten years.

The common thread these organizations share is they are tackling high-use issues in different ways. That includes everything from small, wearable, injectable devices (Enable Injections) that can be used for a multitude of conditions, to analyzing peoples sweat to ensure proper medication dosing (Eccrine Systems).

One of the most interesting might be Sense Diagnostics because their simple device addresses a huge need: stroke detection. Right now there isnt a good way to tell which kind of stroke (transient ischemic, ischemic, or hemorrhagic) someone is having in the field. An ambulance with this non-invasive device will be able to quickly diagnose which stroke is occuring, allowing them to begin the best possible treatment immediately.

As people begin living longer, well see that the traditional approach to education and work must change. A longer living workforce will be more likely to need to reskill for second and third careers.

Private equity firm Thoma Bravo is buying Instructure (makers of the popular Canvas Learning Management System) for $2 billion, precisely because of the projected growth and opportunity in education as people extend their careers.

Of course, four-year higher education will still exist. But new avenues and approaches to learning will emerge as supplemental or alternative ways of reskilling for jobs that will target people in their 60s, 70s, and 80s.

Curricula will obviously also have to adapt, becoming more flexible, personalized, and life-long. Being able to brush up every three months on relevant skills via a subscription model may be a better future model for education than entering a full-time program. Most of the marketing opportunities will be around aiding employers, because they have the budgets and the competition for retention.

Living longer changes a persons entire financial strategy.

Most standard retirement principles assume that retirement will last a maximum of 30 years. The commonly-used "4% rule" of retirement is an example of this. However, if you live to 100 or beyond, your retirement could last 35 years, 40 years, or longer, said Nathan Hamilton, director and industry analyst at The Ascent from The Motley Fool.

A deferred annuity could be worth a look. Essentially, you put some money into an annuity when you first retire (or earlier), but that won't start paying out until a certain agesay, 80 or 85. The idea is that even if your retirement nest egg is getting low as you get older, this move guarantees you a predictable income stream for life.

How we invest may also change as we look to create steady income streams that kick in throughout retirement rather than just upfront. This also may inevitably cause people to work later and longer especially as our workforce trends farther away from physical labor to more mental and creative labor.

The biggest takeaway here isnt that living longer will impact one thing. It will impact everything.

As humans, we need to think about that for ourselves and our future generations. And as marketers and entrepreneurs, we can start thinking about ways we can make that reality better, more productive, and more secure for people.

Go here to read the rest:
Marketing To 100-Year-Olds: How Longevity Will Transform Finance, Healthcare And Education - Forbes