StemCell Therapy

With the help of Howell, weve put together some tips to help you deal with the holiday season.

Theres something about the holidays that makes us want to indulge a little, and rightly so. Its a time for fun, frivolity and enjoying quality time with good friends and good food. But, as tempting as it is, snacking on fruit mince pies or digging into a festive pudding is a big no-no.

Howell says arthritis sufferers should be really careful about what they eat during the festive period, adding that the types of food traditionally eaten at or associated with Christmas aggravate arthritis symptoms.

Every Christmas meal Ive ever had has been packed with ham, sausages, alcohol, chocolate, soft drink and bread, he says. Christmas lunches around Australia are full of sugar, saturated fats, refined carbohydrates, gluten and alcohol all of which are an arthritis sufferers worst nightmare.

Howell adds poor food choices can cause painful arthritis flare-ups, and even more serious health issues in the long-term.

If youre visiting family or friends overseas during the Christmas break and take arthritis medication, make sure you have a doctors certificate with you, Howell advises. You dont want to be caught in a situation where you cant take your meds with you.

A change in weather or humidity can also affect arthritis. Plan ahead and ensure you dress appropriately for the trip.

Howells biggest piece of advice for arthritis sufferers is to stay positive during the Christmas period.

Arthritis may stop you from doing a lot of things at Christmas, he says. You may not be able to eat exactly what you want or be able to participate in the family backyard cricket tournament. But its important to stay positive, especially during Christmas!

Howell recommends talking with your loved ones and suggesting activities that everyone can join in on, such as board games or cards.

Important information: The information provided on this website is of a general nature and information purposes only. It does not take into account your personal health requirements or existing medical conditions. It is not personalised health advice and must not be relied upon as such. Before making any decisions about your health or changes to medication, diet and exercise routines you should determine whether the information is appropriate in terms of your particular circumstances and seek advice from a medical professional.

Link:
How to manage arthritis flare-ups during the holidays - Starts at 60

The "Pain Management Drugs Market - Forecasts from 2019 to 2024" report has been added to ResearchAndMarkets.com's offering.

The pain management drugs market was valued at US$101.189 billion in 2018 and is anticipated to grow at a CAGR of 5.61% to reach a market size of US$140.371 billion by 2024.

The growing geriatric population suffering from pain related to joints and chronic diseases are driving the growth of the global pain management market in the forecast period. Other factors include the prevalence of chronic diseases, rising healthcare expenditures, an increase in the number of accidents and increasing surgical procedures. However, the availability of substitutes such as pain relief devices is hampering the growth of the global pain management drugs market in the forecast period.

Geographically, North America is expected to hold a significant market share owing to the highest health expenditure of the United States in addition to effective disease management owing to the prevalence of chronic diseases in this region.

Report Scope

This report is an exhaustive study that aims to present the key market trends through various chapters focusing on different aspects of the market. The study provides a detailed market overview through the market dynamics sections which detail key market, drivers, restraints, and opportunities in the current market. The report analyzes key opportunity regional markets, and the current technology penetration through lifecycle analysis. The report also analyzes the market through comprehensive market segmentation by drug type, by indication, and by geography.

The pain management drugs market has been segmented based on drug type, indication, and geography. Based on drug type, the market has been segmented into nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, acetaminophen, antidepressants, and anticonvulsant drugs. On the basis of indication, the market has been segmented into cancer, rheumatoid arthritis, chronic back pain, post-operative pain, and others.

Regional analysis has been provided with detailed analysis and forecast for the period 2018 to 2024. The global market has been broken down into North America, South America, Europe, Middle East and Africa (MEA), and the Asia Pacific regions. The report also analyzes 15 major countries across these regions with thorough analysis and forecast along with prevailing market trends and opportunities which each of these countries present for the manufacturers.

Major players in the pain management drugs market have been covered along with their relative competitive position and strategies. The report also mentions recent deals and investments of different market players over the last year. The company profiles section details the business overview, financial performance for the past three years, key products and services being offered along with the recent developments of these important players in the pain management drugs market.

Key Topics Covered

1. INTRODUCTION

2. RESEARCH METHODOLOGY

2.1. Research Design

2.2. Secondary Sources

3. EXECUTIVE SUMMARY

4. MARKET DYNAMICS

4.1. Market Segmentation

4.2. Market Drivers

4.3. Market Restraints

4.4. Market Opportunities

4.5. Porter's Five Forces Analysis

4.5.1. Bargaining Power of Suppliers

4.5.2. Bargaining Power of Buyers

4.5.3. Threat of New Entrants

4.5.4. Threat of Substitutes

4.5.5. Competitive Rivalry in the Industry

4.6. Life Cycle Analysis - Regional Snapshot

4.7. Market Attractiveness

5. PAIN MANAGEMENT DRUGS MARKET BY DRUG TYPE

5.1. Nonsteroidal anti-inflammatory drugs (NSAIDs)

5.2. Corticosteroids

5.3. Acetaminophen

5.4. Antidepressants

5.5. Anticonvulsant drugs

6. PAIN MANAGEMENT DRUGS MARKET BY INDICATION

6.1. Cancer

6.2. Rheumatoid Arthritis

6.3. Chronic Back Pain

6.4. Post-Operative Pain

6.5. Others

7. PAIN MANAGEMENT DRUGS MARKET BY GEOGRAPHY

7.1. North America

7.1.1. USA

7.1.2. Canada

7.1.3. Mexico

7.2. South America

7.2.1. Brazil

7.2.2. Argentina

7.2.3. Others

7.3. Europe

7.3.1. Germany

7.3.2. United Kingdom

7.3.3. France

7.3.4. Spain

7.3.5. Others

7.4. Middle East and Africa

7.4.1. Saudi Arabia

7.4.2. Israel

7.4.3. Others

7.5. Asia Pacific

7.5.1. China

7.5.2. Japan

7.5.3. India

7.5.4. South Korea

7.5.5. Others

8. COMPETITIVE INTELLIGENCE

8.1. Competitive Benchmarking and Analysis

8.2. Strategies of Key Players

Story continues

8.3. Recent Investments and Deals

9. COMPANY PROFILES

9.1. Novartis Pharmaceuticals Corporation

9.2. Eli Lilly and Company

9.3. Amgen Inc.

9.4. GlaxoSmithKline plc

9.5. AbbVie Inc.

9.6. Merck & Co., Inc.

9.7. Sanofi

9.8. F. Hoffmann-La Roche Ltd.

9.9. Pfizer Inc.

9.10. Purdue Pharma L.P.

For more information about this report visit https://www.researchandmarkets.com/r/yq0q5w

View source version on businesswire.com: https://www.businesswire.com/news/home/20191223005511/en/

Contacts

ResearchAndMarkets.comLaura Wood, Senior Press Managerpress@researchandmarkets.com For E.S.T Office Hours Call 1-917-300-0470For U.S./CAN Toll Free Call 1-800-526-8630For GMT Office Hours Call +353-1-416-8900

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Analysis on the World's $140+ Billion Pain Management Drugs Market, 2019-2024 - Featuring Novartis, Eli Lilly, Amgen, GSK, AbbVie, and More -...

"When you become something on the internet and not something in real life," Clairo explains, "It's this very strange cognitive dissonance where you're like, 'Well, is something actually happening, or am I dreaming that people know who I am?' "

Clairo wasn't dreaming. She started college shortly after uploading a song called "Pretty Girl" to YouTube that same week, her bedroom music video reached a million views. Today, it has over 40 million views, and she's launched an entire music career from her viral success. She's appeared on late night television stages, played Coachella and is going on tour with Tame Impala in 2020. Clairo even produced her debut full-length album, Immunity, with a little help from Rostam Batmanglij.

We'll talk about how the former Vampire Weekend member reached out to Clairo on Instagram after hearing her 2017 song, "Flaming Hot Cheetos," how "Sinking" is a sexy song about rheumatoid arthritis ("Which is hilarious," she adds) and how she keeps up with her fans in relation to her rapidly rising profile. Hear the conversation in the player above, starting off with a live in-studio performance of "Bags."

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From 'Pretty Girl' To 'Immunity': Clairo On Her Rapid Rise : World Cafe - NPR

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The monthly joint mixer for the Coral Gables Bar Association and the Rotary Club of Coral Gables, held the second Wednesday of every month, had a twist in December.

That get together, held at Tapeo Eatery & Bar on Giralda, also served as a toy drive for three different organizations: the Marines Toys for Tots, Lighthouse for the Blind and the Coral Gables Free Childrens Dental Clinic for its holiday kids party. Among the many enjoying the event were RCCG president-elect Kelly Garces, Hadley Williams, Greg Martini, Walter Alvarez and Carol Brock.

Speaking of toy drives, Scott and Belinda Sime held their annual holiday party and toy drive, which is where many of the toys collected from the mixer were dropped off. The Simes party always is one that collects several hundred toys every year and is one of the best parties of the season for a cause. In addition to the Simes home. Toys were dropped off as Channel 10s Big Bus Toys for Tots caravan traveled the county with Jacey Birch and Eric Yutzy.

The Mitchell and West Family Fun 5K was one of many events held in front of Coral Gables City Hall on a picture perfect day. PJ Mitchell and Spencer West started this event years ago to raise funds for Alzheimers and now support various causes. This year the Coral Gables Womans Club Children Dental Clinic. The women of this club are everywhere and were among the many hundreds dressed in Santa and holiday attire who ran to support the Arthritis Foundation the morning of Dec. 8 at The Falls. The is the longest-running, holiday-themed 5K race series anywhere and it is no wonder why. It is hilarious. Two of the funniest were Eric Bradley and Phong Truong with their antler headpieces and colorful tutus.

CGWC had raised $1,000 for the Run at a Gringo Bongo fundraiser to match the annual $1,000 donation for a total gift of $2,000 that they presented at the race.

Representing the club that morning with this writer were board member Donna Myrill and dental clinic director Dr. Iris Torres. Club president Arely Ruiz also was on hand to emcee the event for the Foundations outgoing eecutive director and CGWC member Lisa Boccia.

The Arthritis Foundation is one close to the heart of this womans club whose past president Mireya Kilmon has been a spokesperson for the organization and has suffered with arthritis for years.

Speaking of events, Coral Gables Womans Club had two fundraisers just days before that weekend on Dec. 3, the club coordinated its monthly Gringo Bingo hosted by Clutch Burger to raise funds for the Junior Orange Bowl Festival and then two days later had a Prohibition Repeal Speakeasy Party at their clubhouse to benefit the Coral Gables Childrens Dental Clinic that serves currently 600 children of the working poor.

The Junior Orange Bowl, whose numerous events showcase our youth, and the Womans Clubs Dental Clinic and its Childrens Festival both serve our young people in their own unique ways. It was especially fun to have the JOBCs Youth Ambassadors and Jobie at Gringo Bingo to promote the festival and the JOBC Parade held Dec. 15.

Speaking of the JOBC, the festivals annual Junior Orange Bowl Parade was one of the best in years with a new date that certainly made it easier for visiting and local bands to participate. Coming off that event, the committee goes right into the JOBCs International Tennis Tournament (Dec. 14-23); the Junior Orange Bowls annual National Basketball Classic at Miami Palmetto High School on Dec. 27, 28 and 30, and the International Golf Tournament, Jan. 2-6, 2020. For more on these and other JOBC events, visit http://www.jrorangebowl.org.

Finally, save the date, Jan. 7, for the Gringo Bingo (7-9 p.m.). That night CGWC will direct the proceeds to Joshuas Heart Foundation. The Coral Gables Womans Club is extremely grateful for Clutch Burgers generous support in hosting these monthly events. As always, Clutch Burger owner Steven Bradley will entertain and call bingo while celebrity DJ Germain will once again donate his services providing music adding to the overall party atmosphere at these games.. For tickets, send email to gloria@cnews.net.

Until next time, keep making each day count.

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Gables Rotary and Bar Association mixer and toy drive benefits many - Miami's Community Newspapers

News Release

Monday, December 23, 2019

Mutations in the RIPK1 gene responsible for CRIA syndrome.

Over the last 20 years, three families have been unsuspectingly linked by an unknown illness. Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and other organizations have now identified the cause of the illness, a new disease called CRIA syndrome. The results were published in the journal Nature.

NHGRI scientific director Daniel Kastner, M.D., Ph.D., a pioneer in the field of autoinflammatory diseases, and his team discovered CRIA, which has symptoms including fevers, swollen lymph nodes, severe abdominal pain, gastrointestinal problems, headaches and, in some cases, abnormally enlarged spleen and liver.

The disorder has characteristics typical of an autoinflammatory disease, where the immune system appears to be activated without any apparent trigger. Although the condition is not life-threatening, patients have persistent fever and swollen lymph nodes from childhood to old age, as well as other symptoms that can lead to lifelong pain and disability.

When confronted by patients symptoms, who were first seen at the NIH Clinical Center, researchers looked for infections and cancer as the cause. After those were ruled out, they sought answers in the genome, a persons complete set of DNA. Kastner and his team sequenced gene regions across the genome and discovered only one gene RIPK1 to be consistently different in all patients.

Researchers identified a specific type of variation in the patients: a single DNA letter at a specific location incorrectly changed. This change can alter the amino acid added to the encoded protein. These are called "missense" mutations.

Remarkably, each of the three families had its own unique missense mutation affecting the very same DNA letter in the RIPK1 gene. Each affected person had one mutant and one normal copy of the gene, while the unaffected family members had two normal copies of the gene.

The researchers also looked at 554 people with sporadic unexplained fever, swollen glands and other symptoms or diseases, and then at over a quarter million people from public sequence databases to see if they encountered the same RIPK1 mutations. When they did not find such mutations elsewhere, it was clear that they were onto something new.

"It was as if lightning had struck three times in the same place," said Kastner, who led the NHGRI team. "This discovery underscores the tremendous power of combining astute clinical observation, state-of-the-art DNA sequencing, and the sharing of sequence data in large publicly-accessible databases. We live in a very special time."

The RIPK1 gene encodes for the RIPK1 protein, which is involved in the bodys response to inflammation and programmed cell death. To make sure that RIPK1 action does not initiate inflammation and cell death in all cells, another protein cuts the RIPK1 protein at a specific location in the protein sequence. The research team noticed that all the mutations in CRIA patients occur at the location where RIPK1 usually gets cut, resulting in an uncuttable, seemingly indestructible RIPK1 protein.

This suggests that cutting RIPK1, thereby disarming it, is crucial to controlling cell death and inflammation. Recognizing this cause-effect relationship, Kastners team named the resulting disease cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome.

Although the researchers made the connection between CRIA syndrome and RIPK1 mutations, they still needed to understand the molecular mechanisms involved in the disease. To do this, Kastner and his team collaborated with Najoua Laloui, Ph.D., and John Silke, Ph.D., at the Walter and Eliza Hall Institute in Australia, who made specialized mouse models with similar RIPK1 mutations as seen in CRIA patients.

The Australian team discovered that mouse embryos with two mutant copies of RIPK1 (and no normal copy) did not survive in the uterus due to excessive cell death signals, which further confirmed the importance of cutting RIPK1 to limit its function in normal cells. However, mice bearing one mutant copy of RIPK1 and one normal copy, as is the case for CRIA patients, were mostly normal but had heightened responses to a variety of inflammatory stimuli, which the researchers think may suggest a possible mechanism for how the human disease occurs.

Kastner and his team worked to find a treatment for CRIA syndrome. Seven patients with the condition were given therapies that are known to reduce inflammation. While drugs such as etanercept and anakinra, which are routinely used to treat autoinflammatory and chronic diseases such as rheumatoid arthritis, had little effect on the patients, one biological drug called tocilizumab did. Tocilizumab, a drug that suppresses the immune system, reduced the severity and frequency of CRIA syndrome symptoms in five out of seven patients in some cases with life-changing effects.

Hirotsugu Oda, M.D., Ph.D., a post-doctoral researcher in Kastners laboratory and co-first author of the paper, said: "As a physician-scientist, the most thrilling experience to me was to hear the mother of a CRIA patient say that her son was a completely different, healthy child after the tocilizumab treatment. Through the genetic diagnosis, we were able to contribute to the treatment of a few patients. This is, after all, the ultimate goal."

Researchers are now trying to understand the detailed molecular mechanism that enables tocilizumab to treat CRIA. Specific inhibitors of RIPK1, which are under development, may also hold promise in both CRIA and other seemingly intractable inflammatory conditions.

The study included collaborations with the following NIH institutions: National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH Clinical Center, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases and NIH Intramural Sequencing Center.

About the National Human Genome Research Institute (NHGRI) is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at:www.genome.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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NIH researchers discover new autoinflammatory disease and uncover its biological cause - National Institutes of Health

An Up to Date Report onRheumatoid Arthritis and Lupus Treatments Market size | Industry Segment by Applications (Hospitals and Clinics, Ambulatory Surgery Centers and Homecare Settings), by Type (Rheumatoid Arthritis Treatments and Lupus Treatments), Regional Outlook, Market Demand, Latest Trends, Rheumatoid Arthritis and Lupus Treatments Industry Share & Revenue by Manufacturers, Company Profiles, Growth Forecasts 2025.Analyzes current market size and upcoming 5 years growth of this industry.

In accordance with the Rheumatoid Arthritis and Lupus Treatments market report, the industry is anticipated to amass returns while accounting a profitable yearly growth rate in the predictable time period. It provides an outline of Rheumatoid Arthritis and Lupus Treatments industry and also offers details related to the valuation the Rheumatoid Arthritis and Lupus Treatments market currently holds, breakdown of the Rheumatoid Arthritis and Lupus Treatments market, along with the growth opportunities in the business vertical.

Repot Scope:

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Rheumatoid Arthritis and Lupus Treatments Market Statistics by Types:

Ideas and concepts covered in the report:

The region-based analysis of the Rheumatoid Arthritis and Lupus Treatments market

A brief of the market segmentation

Factors and challenges described in the report

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Analysis of the competitors in the industry:

The report also speaks about several other information such as assessment of the competitive landscape, data related to the market concentration rate and concentration ratio in the upcoming years.

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Rheumatoid Arthritis and Lupus Treatments Market Research Report, Growth Forecas - News by aeresearch

DetailsCategory: AntibodiesPublished on Friday, 20 December 2019 13:14Hits: 658

- BLISS-LN achieves primary endpoint and all major secondary endpoints

- On-track for regulatory submission during the first half of 2020

LONDON, UK I December 18, 2019 I GSK today announced positive headline results for intravenous (IV) Benlysta (belimumab) in the largest controlled phase 3 study in active lupus nephritis (LN), an inflammation of the kidneys caused by systemic lupus erythematosus (SLE) which can lead to end-stage kidney disease.

The Efficacy and Safety of Belimumab in Patients with Active Lupus Nephritis (BLISS-LN) study, involving 448 patients, met its primary endpoint demonstrating that a statistically significant greater number of patients achieved Primary Efficacy Renal Response (PERR) over two years when treated with belimumab plus standard therapy compared to placebo plus standard therapy in adults with active LN (43% vs 32%, odds ratio (95% CI) 1.55 (1.04, 2.32), p=0.0311).

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK said: "Lupus nephritis is one of the most common and serious complications of SLE, occurring in up to 60% of adult patients. The results of the BLISS-LN study show that Benlysta could make a clinically meaningful improvement to the lives of these patients who currently have limited treatment options."

Dr Richard Furie,Chief of the Division of Rheumatology and Professor at the Feinstein Institutes atNorthwell Health and Lead Investigator of BLISS-LN said: "My journey with Benlysta began nearly twenty years ago when we performed the very first clinical research trial in lupus patients. To see it culminate in a successful phase 3 lupus nephritis study is a key achievement as the inadequate response of our patients with kidney disease to conventional treatment has long been an area in need of major improvement."

Belimumab also demonstrated statistical significance compared to placebo across all four major secondary endpoints: Complete Renal Response (CRR) after two years (the most stringent measure of renal response), Ordinal Renal Response (ORR) after two years, PERR after one year, and the time to death or renal-related event. In BLISS-LN, safety results for patients treated with belimumab were generally comparable to patients treated with placebo plus standard therapy. The safety results are consistent with the known profile of belimumab.

Benlysta is currently not recommended for use in severe active lupus nephritis anywhere in the world because it has not been previously evaluated in these patients. Based on these positive phase 3 data, GSK plans to progress regulatory submissions in the first half of 2020 to seek an update to the prescribing information.

The full results will be submitted for future presentation at upcoming scientific meetings and in peer-reviewed publications.

About lupus nephritisSystemic lupus erythematosus (SLE), the most common form of lupus, is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time including painful or swollen joints, extreme fatigue, unexplained fever, skin rashes and organ damage. In lupus nephritis (LN), SLE causes kidney inflammation, which can lead to end-stage kidney disease. Despite improvements in both diagnosis and treatment over the last few decades, LN remains an indicator of poor prognosis.1,2 Manifestations of LN include proteinuria, elevations in serum creatinine, and the presence of urinary sediment.

About BLISS-LNBLISS-LN,which enrolled 448 adult patients, was a phase 3, 104-week, randomised, double-blind, placebo-controlled post-approval commitment study to evaluate the efficacy and safety of IV belimumab 10 mg/kg plus standard therapy (mycophenolate mofentil for induction and maintenance, or cyclophosphamide for induction followed by azathioprine for maintenance, plus steroids) compared to placebo plus standard therapy in adult patients with active lupus nephritis. Active lupus nephritis was confirmed by kidney biopsy during screening visit using the 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, and clinically active kidney disease.

The primary endpoint PERR was defined as estimated Glomerular Filtration Rate (eGFR) 60 mL/min/1.73m2 or no decrease in eGFR from pre-flare of > 20%; and urinary protein:creatinine ratio (uPCR) 0.7; and not a treatment failure. The most stringent secondary endpoint CRR was defined as eGFR is no more than 10% below the pre-flare value or within normal range; and uPCR < 0.5; and not a treatment failure. ORR was defined as complete, partial or no response.

About Benlysta (belimumab)Benlysta, a BLyS-specific inhibitor, is a human monoclonal antibody that binds to soluble BLyS. Benlysta does not bind B cells directly. By binding BLyS, Benlysta inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

The current US and EU indication for Benlysta are summarised below:

In the US, "Benlysta is indicated for the treatment of patients aged 5 years and older with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations."

Full US prescribing information including Medication Guide is available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Benlysta/pdf/BENLYSTA-PI-MG.PDF

In the EU, "Benlysta is indicated as "add-on therapy in patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity (e.g., positive anti-dsDNA and low complement) despite standard therapy."

The Precaution and Warnings for Benlysta includes information that "Benlysta has not been studied in the following adult and paediatric patient groups, and is not recommended: severe active central nervous system lupus; severe active lupus nephritis; HIV; a history of, or current, hepatitis B or C; hypogammaglobulinaenia (IgG < 400mg/dl) or IgA deficiency (IgA < 10 mg/dl); a history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant."

The EU Summary of Product Characteristics for Benlysta is available on: http://www.ema.europa.eu

Benlysta is available as an intravenous and a subcutaneous formulation. The Benlysta subcutaneous formulation is not approved for use in children.

GSK's commitment to immunologyGSK is focused on the research and development of medicines for immune-mediated diseases, such as lupus and rheumatoid arthritis, that are responsible for a significant health burden to patients and society. Our world-leading scientists are focusing research on the biology of the immune system with the aim to develop immunological-based medicines that have the potential to alter the course of inflammatory disease. As the only company with a biological treatment approved for adult and paediatric lupus, GSK is leading the way to help patients and their families manage this chronic, inflammatory autoimmune disease. Our aim is to develop transformational medicines that can alter the course of inflammatory disease to help people live their best day, every day.

SOURCE: GlaxoSmithKline

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GSK announces positive headline results in phase 3 study of Benlysta in patients with lupus nephritis | Antibodies | News Channels -...

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that KEYTRUDA, Mercks anti-PD-1 therapy, received new approvals from the Japan Pharmaceuticals and Medical Devices Agency (PMDA) in advanced renal cell carcinoma (RCC) and head and neck cancer for the following additional indications in Japan:

Advanced renal cell carcinoma and head and neck cancer have historically been associated with poor outcomes and new treatment options are needed in Japan, said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. Todays approval of three new first-line KEYTRUDA regimens represents a significant milestone for patients diagnosed with these aggressive forms of cancer and will provide patients in Japan with important alternatives to standard therapies.

The approval for KEYTRUDA in combination with axitinib for radically unresectable or metastatic RCC is based on results from the KEYNOTE-426 trial, in which KEYTRUDA in combination with axitinib demonstrated statistically significant improvements in the dual primary endpoints of overall survival (OS) (HR=0.53 [95% CI, 0.38-0.74]; p=0.00005) and progression-free survival (PFS) (HR=0.69 [95% CI, 0.56-0.84]; p=0.00012) compared to sunitinib monotherapy.

The approval for KEYTRUDA for the first-line treatment of patients with recurrent or distant metastatic head and neck cancer is based on results from the Phase 3 KEYNOTE-048 trial which evaluated KEYTRUDA in combination with platinum and 5-fluorouracil (5-FU), or KEYTRUDA monotherapy compared with standard treatment (cetuximab in combination with platinum and 5-FU), as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma. In the trial, KEYTRUDA in combination with platinum and 5-FU significantly prolonged OS (HR=0.77 [95% CI, 0.63-0.93]; p=0.00335) compared with standard treatment. As monotherapy, KEYTRUDA demonstrated non-inferiority (HR=0.85 [95% CI, 0.71-1.03]; p=0.00014) compared with standard treatment. Additionally, KEYTRUDA monotherapy demonstrated a statistically significant improvement in OS in patients whose tumors expressed PD-L1 (CPS 1) compared with standard treatment.

Last year, an estimated 850,000 new cancer diagnoses were made in Japan alone, underscoring the critical need for innovative research and development to identify additional treatment options, said Jannie Oosthuizen, managing director of MSD in Japan. The new approvals of KEYTRUDA in advanced renal cell carcinoma and head and neck cancer build on previous approvals in melanoma, advanced non-small cell lung cancer and advanced MSI-H cancers, allowing us to bring KEYTRUDA to even more patients in Japan.

Renal cell carcinoma is by far the most common type of kidney cancer, with approximately 403,000 cases of kidney cancer diagnosed worldwide in 2018 and about 175,000 deaths from the disease. In Japan, it is estimated there were more than 24,000 people diagnosed with kidney cancer, and more than 8,000 deaths occurred in 2018.

Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. It is estimated that there were more than 705,000 new cases of head and neck cancer diagnosed and over 358,000 deaths from the disease worldwide in 2018. In Japan, it is estimated that more than 22,000 new cases of head and neck cancer were diagnosed, and more than 8,000 deaths occurred in 2018.

About KEYTRUDA (pembrolizumab) Injection

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 patients likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected Indications for KEYTRUDA (pembrolizumab) in the U.S.

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 one 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.

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 hypophysitis, thyroid disorders, and type 1 diabetes mellitus. 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 hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 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; 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%).

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%).

Adverse reactions occurring in patients with hepatocellular carcinoma (HCC) were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 34) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 34) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 34) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

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Merck's KEYTRUDA (pembrolizumab) Approved in Japan for Three New First-Line Indications Across Advanced Renal Cell Carcinoma (RCC) and Recurrent or...

"Metastatic urothelial cancer is an aggressive and devastating disease with limited treatment options, and the approval of PADCEV is a significant advance for these patients who previously had limited options after initial therapies failed," said Jonathan E. Rosenberg, M.D., Medical Oncologist, Chief, Genitourinary Medical Oncology Service, Memorial Sloan Kettering Cancer Center in New York. "The PADCEV clinical trial enrolled a range of patients whose cancer was difficult to treat, including those whose disease had spread to the liver."

"The FDA approval of PADCEV is welcome news for patients with bladder cancer," said Andrea Maddox-Smith, Chief Executive Officer, Bladder Cancer Advocacy Network. "Though new medicines for bladder cancer have been approved in recent years, most people living with advanced stages of this disease face a difficult journey with few treatment options."

"This approval underscores our commitment to develop novel medicines that address unmet patient needs, and we're grateful to the patients and physicians whose participation led to this outcome," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas.

"PADCEV is the first antibody-drug conjugate approved for patients facing this aggressive disease, and it is the culmination of years of innovative work on this technology," said Roger Dansey, M.D., Chief Medical Officer, Seattle Genetics.

PADCEV was evaluated in the pivotal trial EV-201, a single-arm phase 2 multi-center trial that enrolled 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy.1 In the study, the primary endpoint of confirmed objective response rate (ORR) was 44 percent per blinded independent central review (55/125; 95% Confidence Interval [CI]: 35.1, 53.2). Among patients treated with the single agent PADCEV, 12 percent (15/125) experienced a complete response, meaning no cancer could be detected at the time of assessment, and 32 percent (40/125) experienced a partial response, meaning a decrease in tumor size or extent of cancer in the body. The median duration of response (DoR), a secondary endpoint, was 7.6 months (95% CI: 6.3, not estimable [NE]). 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%). The most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). 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%).

The FDA's Accelerated Approval Program allows approval of a medicine based on a surrogate endpoint if the medicine fills an unmet medical need for a serious condition.A global, randomized phase 3 confirmatory clinical trial (EV-301) is underway and is also intended to support global registrations.

About PADCEV 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 Nonclinical 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). PADCEV is co-developed by Astellas and Seattle Genetics.

PADCEV Support Solutions offers access and reimbursement support to help patients access PADCEV. For more information, go to PADCEV Support Solutions at PADCEVSupportSolutions.com.

About Bladder and Urothelial CancerApproximately 80,000 people in the U.S. will be diagnosed with bladder cancer this year.4 Urothelial cancer accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.5

Important Safety Information

Warnings and Precautions

Adverse Reactions Serious 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 Abnormalities In 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 Astellas Astellas 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 Seattle Genetics Seattle Genetics, Inc. is an emerging multi-product, global biotechnology company that develops and commercializes transformative therapies targeting cancer to make a meaningful difference in people's lives. The company is headquartered in Bothell, Washington, and has a European office in Switzerland. For more information on our robust pipeline, visit http://www.seattlegenetics.comand follow @SeattleGenetics on Twitter.

About the Astellas and Seattle Genetics CollaborationSeattle Genetics and Astellas are co-developing PADCEV (enfortumab vedotin) 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.

Astellas Cautionary Notes In 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.

Seattle Genetics Forward Looking StatementsCertain statements made in this press release are forward looking, such as those, among others, relating to the continued FDA approval of PADCEV (enfortumab vedotin-ejfv) for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting; the conduct of an ongoing randomized phase 3 confirmatory clinical trial (EV-301) intended to verify the clinical benefit of PADCEV and support global registrations; and the therapeutic potential of PADCEV including its efficacy, safety and therapeutic uses. 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 EV-301 and subsequent clinical trials may fail to establish sufficient efficacy; that adverse events or safety signals may occur; that utilization and adoption of PADCEV by prescribing physicians may be limited by the availability and extent of reimbursement or other factors; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended September 30, 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.

1 Padcev [package insert]. Northbrook, IL: Astellas, Inc. 2 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):2592600.3 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. 4 American Society of Clinical Oncology. Bladder cancer: introduction (10-2017). https://www.cancer.net/cance rtypes/bladdercancer/introduction. Accessed 05-09-2019. 5National 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.

SOURCE Astellas Pharma US, Inc.

https://www.astellas.com

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FDA Grants Accelerated Approval to Astellas' and Seattle Genetics' PADCEV (enfortumab vedotin-ejfv) for People with Locally Advanced or Metastatic...

Unlike almost every other organ, the mammary gland does not develop until after birth. And its unusually dynamic, shape-shifting during menstrual cycles, puberty, pregnancy, and lactation.

These changes require energy. In a study usinga new, genetically altered mouse model, researchers led by Rumela Chakrabarti of Penns School of Veterinary Medicine haveuncovered a key protein involved in supplying the mammary gland with fuel during puberty. Its a protein that her group had earlier shown to play a role in triple-negative breast cancer (TNBC), a particularly aggressive form of the disease.

Besides illuminating an important feature of mammalian biological development, the findings also give reassurance that targeting this protein, known as deltaNp63, to treat cancer in adults could be done without interfering with critical developmental stages that occur later in life.

Creating a new mouse model that allows us to control when p63 is expressed enabled us to study this molecule in different developmental stages, Chakrabarti says of the work, published in the journal FEBS Letters. The fact that it is not required later on after puberty means that its a viable drug target for triple-negative breast cancer. And we think it could be applicable to other cancers, like squamous cell carcinomas and esophageal cancer as well.

Chakrabarti has focused on this molecule since her postdoctoral fellowship, revealing different features of its involvement in the mammary gland stem cells that give rise to every other cell type in the mammary gland tissue. In 2014, Chakrabarti and colleagues found it was important in initiating TNBC, and last year they demonstrated that it also acts to direct a type of immune cell to breast tumors, serving to aggravate the progression and spread of cancer.

Weve found that this molecule is like a master regulator, says Chakrabarti. It can regulate the tumor cells stem cell activity, and it can regulate the immune cells around the tumor cells. But we also wanted to know how it acted in normal cells.

To do that, the researchers fashioned a new strain of mice in which they could deplete the animals of deltaNp63 as desired. With this mouse model in hand, they were able to assess how deleting that gene affected the mammary gland.

While inducing the deletion of deltaNp63 during pregnancy and adulthood had no significant effect on mammary gland development and function, the team found significant impacts arose when deletion occurred during puberty.

It may be that the initial burst of energy that is required during puberty depends on deltaNp63, but once you get through that, it isnt as critical, says Chakrabarti.

Losing the protein during puberty led to a reduction in energy production in the mammary gland cells and caused mammary gland ducts to be malformed. Further analysis suggests that deltaNp63 likely activates other proteins that are involved in both cellular metabolism and in the organization of cell structure during puberty.

We already knew that p63 was important for mammary gland stem cells, but we didnt know that it was involved in regulating the cells metabolism, Chakrabarti says. Mammary stem cells have a high energy need during the extensive tissue remodeling that occurs during puberty. Cancer cells also have a high energy need. So this finding helps tie together a number of roles that p63 seems to be playing in the mammary gland.

In follow-up work, Chakrabartis lab is investigating the connection between metabolism and TNBC, with an eye toward pursuing deltaNp63 as a possible therapeutic target to slow down the spread of disease.

Rumela Chakrabarti is an assistant professor of biomedical sciences in the University of Pennsylvania School of Veterinary Medicine.

Chakrabartis coauthors from Penn Vet were first author Sushil Kumar, Ajeya Nandi, and Aakash Mahesh. In addition, Satrajit Sinha of the State University of New York at Buffalo and Elsa Flores of the Moffit Cancer Center coauthored the paper.

Support for the study came from the Penn Vet Comparative Pathology Core, the Flow Cytometry Core at the University of Pennsylvania and Childrens Hospital of Philadelphia.

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A new role for a triple-negative breast cancer target - Penn: Office of University Communications

Some people believe that it is impossible to ionize water, others believe the product is too good to be true.

It is important to note that the ionization of water can be tested using scientific measuring devices such as pH and ORP meters. According to The Miraculous Properties of Ionized Water, the changes that ionization produceareradical, immediate, and measurable.

Ionized water is the charging of water by creating negative ions (-OH) and positive ions (+OH). They are created through electrolysis and then the ions are separated through a membrane, so the water is negatively charged.

There has been a considerable amount of research conducted on the effects of ionized water. Most of the research has been conducted by the Japanese. All of the research has arrived at the same conclusion: ionized water benefits everything it comes in contact with as long as its used correctly. There is hard scientific evidence to back up this claim.

There are strong detoxing effects of ionized water, which proves it is not like any other water consumed. These detoxing effects are due to the small water-molecule cluster size. Water-molecule cluster size is measured using a Nuclear Magnetic Resonance device. The change in the surface tension of ionized water can also be determined. It is measured in dynes. The lower the surface tension, the smaller the water-molecule clusters.

Water is the most essential element needed by the body; therefore, health begins with water. It is impossible to be truly healthy without being properly hydrated.

When babies are born, their bones are mostly water. They are more pliable at birth than at any other time in their lives. As people grow older, the bones dry out and become brittle. The body takes the calcium from the bones to distribute it to other parts of the body that need it more.

By the age of 65, the average person is 50-70 percent dehydrated.This is whythe elderly are riddled with disease and constipation.

Bone marrow is critical to the immune system because it contains T-cells, B-cells and other cells that together form the immune system. White blood cells produce antibodies that have a multitude of other immune functions. Red blood cells carry oxygen, produce stem cells and blood platelets that allow the blood to clot.

Stem cells are primitive cells that continue to divide into infinity and form any other cell the body needs. These cells are birthed out of bone marrow, which makes hydration critical to the body. It is imperative to keep bone marrow hydrated, cleansed, and rejuvenated for great health and longevity.

Every single organ in the body requires water to properly function to its full capacity. The body is 69 percent water. The brain is 85 percent water, bones 35 percent water, blood 83 percent water, and the liveris90 percent water.

When the body is dehydrated, it puts ones health in immediate danger. Each day people should drink half their body weight in ounces. However, The Miraculous Properties of Ionized Water recommends people drink much more than half their body weight in water because that amount of water is lost through basic functions of the human body, such as urinating, sweating, breathing, and defecating.

The National Research Council guidelines suggest that the body requires one milliliter of water for every calorie of food consumed, which tends to be half of ones body weight. For example, if one weighs 200 pounds, they should drink 100 ounces of water. According to the official report from the National Research Council states that most of this quantity is contained in prepared foods. This implies that people will get the water they need from the foods they eat and drinking water is not necessary.

These types of misconceptions lead people to believe that water is a choice, not a necessity. Digestion is dehydrating and requires a large amount of water from the bodys reserves. Additionally, the typical American diet consists of dry, cooked and processed foods. Raw foods contain significant amounts of water and are better for ones diet.

There are some who believe that water consumed in raw foods is enough to hydrate the body. This is not true. Even if one could eat enough raw foods to hydrate the body, water would still be required to flush the digestive tract between meals. This is one of the healthiest things one can do. None of the bodys processes will function to capacity if the body is not well hydrated.

By Jeanette Vietti

Source:

The Miraculous Properties of Ionized Water

Image Courtesy of Rubbermaid Products Flickr Page Creative Commons License

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Why Proper Hydration Is Necessary for the Body to Function - Guardian Liberty Voice

Aspen Neuroscience, a new biotech company, has raised $6.5 million to develop cell therapies for Parkinsons disease using patients own cells.

The company was co-founded by renowned stem cell scientists Jeanne F. Loring, PhD, and Andres Bratt-Leal, PhD, and initially supported by Summit for Stem Cell, a non-profit organization that provides a variety of services for Parkinsons patients.

Parkinsons hallmark motor symptomsinclude tremor, slowness of movement (bradykinesia), stiffness (rigidity), uncontrollable movements (dyskinesia), and poor balance.

As the disease progresses, patients typically need to gradually increase their dopaminergic therapeutic dose for maximum benefit. Even after that they might sometimes experience reappearance or worsening of symptoms due to diminishing effects of dopaminergic therapy, known was off periods.

Importantly, dopaminergic therapy is delivered to areas of the brain other than the striatum, a key motor control region severely affected in Parkinsons disease. Because of the therapys off-target behavior, patients also may experience side effects such as hallucinations or cognitive impairment.

Aspen wants to combine its expertise in stem cell biology, genomics and neurology and develop the first autologous (self) stem cell-based therapy for Parkinsons disease.

In this type of cell therapy, a patients own cells (usually skin cells) are reprogrammed back into a stem cell-like state, which allows the development of an unlimited source of almost any type of human cell needed, including dopamine-producing neurons, which are those mainly affected by this disorder.

Because these cells are derived from patients, they do not carry the risk of being rejected once re-implanted, eliminating the need for immunosuppressive complementary therapies, which carry serious side effects such as infections and possibly limiting therapeutic potential.

In theory, replacing lost dopaminergic neurons with new stem cell-derived dopamine-producing ones could potentially ease or reverse motor symptoms associated with the disease.

Aspen is developing a restorative, disease modifying autologous neuron therapy for people suffering from Parkinsons disease, Howard J. Federoff, MD, PhD, Aspens CEO, said in a press release.

We are fortunate to have such a high-caliber scientific and medical leadership team to make our treatments a reality. Our cell replacement therapy, which originated in the laboratory of Dr. Jeanne Loring and was later supported by Summit for Stem Cell and its President, Ms. Jenifer Raub, has the potential to release dopamine and reconstruct neural networks where no disease-modifying therapies exist, Federoff said.

The companys lead product (ANPD001) is undergoing investigational new drug (IND)-enabling studies for the treatment of sporadic Parkinsons disease. Aspen experts also are developing a gene-editing treatment (ANPD002) for familial forms of Parkinsons, starting with the most common genetic variant in the GBAgene, which provides instructions to make the enzyme beta-glucocerebrosidase.

The new seed funding round was led by Domain Associates and Axon Ventures, with additional participation from Alexandria Venture Investments, Arch Venture Partners, OrbiMed and Section 32, according to the press release.

With over three years of experience in the medical communications business, Catarina holds a BSc. in Biomedical Sciences and a MSc. in Neurosciences. Apart from writing, she has been involved in patient-oriented translational and clinical research.

Total Posts: 208

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Aspen Neuroscience Receives $6.5M for Parkinson's Stem Cell Therapy - Parkinson's News Today

Liming Wang,1,* Shigao Huang,2,* Shimei Li,1 Ming Li,1 Jun Shi,1 Wen Bai,1 Qianyun Wang,1 Libo Zheng,3 Yongjun Liu3

1Cell Therapy Center, 986 Hospital of Peoples Liberation Army Air Force, Xian, Shaanxi, Peoples Republic of China; 2Cancer Center, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, Peoples Republic of China; 3Stem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Shigao HuangCancer Center, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Room 3013, Building N-22, Taipa, Macau, Peoples Republic of ChinaEmail huangshigao2010@aliyun.comYongjun LiuStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, No. 35, Jinghai 3 Road Economic-Technological Development Area, Beijing, Peoples Republic of ChinaEmail andyliuliu2001@aliyun.com

Background: The traditional anti-inflammation disease-modifying anti-rheumatic drugs (DMARDs) have limited therapeutic effects in rheumatoid arthritis (RA) patients. We previously reported the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSC) treatment in RA patients that were observed for up to 8 months after UC-MSC infusion. The aim of this study is to assess the long-term efficacy and safety of UC-MSC along with DMARDs for the treatment of RA.Methods: 64 RA patients aged 1864 years were recruited in the study. During the treatment, patients were treated with 40 mL UC-MSC suspension product (2 107 cells/20 mL) via intravenous injection immediately after the infusion of 100 mL saline. The serological markers tests were used to assess safety and the 28-joint disease activity score (DAS28) and the Health Assessment Questionnaire (HAQ) to assess efficacy.Results: 1 year and 3 years after UC-MSC cells treatment, the blood routine, liver and kidney function and immunoglobulin examination showed no abnormalities, which were all in the normal range. The ESR, CRP, RF of 1 year and 3 years after treatment and anti-CCP of 3 years after treatment were detected to be lower than that of pretreatment, which showed significant change (P < 0.05). Health index (HAQ) and joint function index (DAS28) decreased 1 year and 3 years after treatment than before treatment (P < 0.05).Conclusion: UC-MSC cells plus DMARDs therapy can be a safe, effective and feasible therapeutic option for RA patients.

Keywords: rheumatoid arthritis, umbilical cord mesenchymal stem cell, cell therapy

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Stem Cell Therapy Market Overview:

The report titled Stem Cell Therapy Market is one of the most comprehensive and important additions to Verified Market Research archive of market research studies. It offers detailed research and analysis of key aspects of the Stem Cell Therapy market. The market analysts authoring this report have provided in-depth information on leading growth drivers, restraints, challenges, trends, and opportunities to offer a complete analysis of the Stem Cell Therapy market. Market participants can use the analysis on market dynamics to plan effective growth strategies and prepare for future challenges beforehand. Each trend of the Stem Cell Therapy market is carefully analyzed and researched about by the market analysts.

Global Stem Cell TherapyMarketwas valued at USD 86.62 million in 2016 and is projected to reach USD 221.03million by 2025, growing at a CAGR of 10.97% from 2017 to 2025.

The report includes detailed analysis of the vendor landscape and thorough company profiling of leading players of the Stem Cell Therapy market.The researchers have considered almost all important parameters for company profiling, including market share, recent development, gross margin, future development plans, product portfolio, production, and revenue.

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Leading players covered in the Stem Cell Therapy market report:

Insight into Competitive Landscape :

Market players need to have a complete picture of the competitive landscape of the Stem Cell Therapy market as it forms an essential tool for them to plan their future strategies accordingly. The report puts forth the key sustainability strategies taken up by the companies and the impact they are likely to have on the Stem Cell Therapy market competition. The report helps the competitors to capitalize on opportunities in the Stem Cell Therapy market and cope up with the existing competition. This will eventually help them to make sound business decisions and generate maximum revenue.

Market Segment Analysis :

The report offers a comprehensive study of product type and application segments of the Stem Cell Therapy market. The segmental analysis provided in the report is based on significant factors such as market share, market size, consumption, production, and growth rate of the market segments studied.Readers of the report are also provided with exhaustive geographical analysis to provide clear understanding of the regional growth of the Stem Cell Therapy market. Developed as well as developing regional markets for Stem Cell Therapy have been deeply studied to help market players identify profit-making opportunities in different regions and countries.

North America (United States, Canada and Mexico)

Asia Pacific (China, Japan, South Korea, India, Australia, Indonesia, Thailand, Malaysia, Philippines and Vietnam)

Middle East and Africa (Turkey, GCC Countries, Egypt and South Africa)

South America (Brazil and others)

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Table of Content

1 Introduction of Stem Cell Therapy Market

1.1 Overview of the Market 1.2 Scope of Report 1.3 Assumptions

2 Executive Summary

3 Research Methodology of Verified Market Research

3.1 Data Mining 3.2 Validation 3.3 Primary Interviews 3.4 List of Data Sources

4 Stem Cell Therapy Market Outlook

4.1 Overview 4.2 Market Dynamics 4.2.1 Drivers 4.2.2 Restraints 4.2.3 Opportunities 4.3 Porters Five Force Model 4.4 Value Chain Analysis

5 Stem Cell Therapy Market, By Deployment Model

5.1 Overview

6 Stem Cell Therapy Market, By Solution

6.1 Overview

7 Stem Cell Therapy Market, By Vertical

7.1 Overview

8 Stem Cell Therapy Market, By Geography

8.1 Overview 8.2 North America 8.2.1 U.S. 8.2.2 Canada 8.2.3 Mexico 8.3 Europe 8.3.1 Germany 8.3.2 U.K. 8.3.3 France 8.3.4 Rest of Europe 8.4 Asia Pacific 8.4.1 China 8.4.2 Japan 8.4.3 India 8.4.4 Rest of Asia Pacific 8.5 Rest of the World 8.5.1 Latin America 8.5.2 Middle East

9 Stem Cell Therapy Market Competitive Landscape

9.1 Overview 9.2 Company Market Ranking 9.3 Key Development Strategies

10 Company Profiles

10.1.1 Overview 10.1.2 Financial Performance 10.1.3 Product Outlook 10.1.4 Key Developments

11 Appendix

11.1 Related Research

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Stem Cell Therapy Market Growth Rate by 2026 Top Key Vendors, Trend, Segmentation, Drivers, Challenges and Forecast - Testifyandrecap

Here we are at the end of yet another year, a year that definitely went by faster than the year before or for that matter the year before that. And as ever at this time of year tis the season for casting ahead and divining what the future holds, delivering lists of top 10s and predictions of what will be hot and what will not.

In some fields, the resultant list will look very much like something delivered by the toss of a coin, but in the science and research areas it is pretty certain what will land in the top two or three subjects.

Number one has got to be climate and the impact of global warming. There is no other area that can match it for the variety and depth of research activity being applied to a whole range of climate-related subjects. And the hard news stories keep tumbling out of this endeavour, helping to show that global changes are taking place due to the alterations in climate that we as humans have set in motion.

One peer-reviewed study about the increasingly rapid loss of ice mass over Greenland was published less than a fortnight before Christmas. It showed that the biggest block of land ice in the northern hemisphere was melting away much faster than expected, seven times faster the study suggests.

Published in the journal Nature, it said the island lost 33 billion tonnes of ice on average during the last decade of the 20th century but the average annual ice loss for the most recent 10 years now stands at 254 billion tonnes of ice a year.

This is just one story and one research area, but climate-related studies arise in many fields from alteration of ocean currents to changed rainfall patterns and from species loss to poor air quality. It is also a subject area that affects us all given the potential of coastal flooding, crop losses and human migration to name but a few possible future impacts.

The impacts for humanity are also there in research into new ways to alter our genetic blueprints. The key to unlocking the potential to overcome gene-based diseases relates CRISPR CAS9, our current best technology for getting into the genome and then adding, deleting or altering individual genes.

It has the potential to reverse disease states by correcting unwanted mutations. It is being used in labs around the world as scientists seek to fully understand the method and apply it to alter genes. It is a powerful research tool, for example to create a mouse model that imitates a human disease state and then developing and testing drugs that might be used in humans. It also allows the researcher to look for any unwanted downstream effects arising from genetic alterations.

There are so many scientists using the CRISPR tools that news reports and discoveries will certainly follow. Yet most research scientists are concerned about the lack of controls or limits on what kind of genetic experiments that might be conducted on the human genome. Too little is known about unexpected problems if a number of genes are altered to eliminate a genetic disorder.

There is also the issue of genetic alteration of the germline, the genetic material that moves across to the next generation. There is currently an international block on germline alterations but that has not stopped at least one researcher who went ahead and created the worlds first two genetically modified humans. Breakthroughs will be delivered all through 2020 it is probably safe to say.

What might come third in this short list is up for grabs, and what might produce the next big scientific discovery could come from any direction. For that reason this report becomes a wish list relevant to Irish research and scientific endeavour related to our engagement with important international research bodies.

One of the most important decisions in this regard brings us closer to membership of Cern, Europes premier nuclear research body. A Dil committee studied the research and commercial potential arising from membership and called on the Government to join Cern as quickly as possible.

Cerns huge atom smasher confirmed the existence of the Higgs Boson, an international effort that involved many countries. Ireland could become more involved in this kind of research if it were a member. The Government has already taken the leap and announced our membership of the European Southern Observatory.

Our astronomers and physicists can now get access to some of the worlds largest telescopes based in Chile. The ESO is also a mill for discoveries and this membership gives us the potential to become international players in this field. And in more familiar territory, the Government has renewed its commitment to invest 100 million in the European Space Agency between now and 2024, a decision that ensures Ireland can bid for commercial contracts and researchers can participate in ESA activities. Our investment pays for itself given Irish companies can share in contracts.

All of the research areas mentioned here show how important it is to internationalise Irelands involvement in science. By doing this, we give more opportunities to promising young Irish scientists and help build a strong international reputation for research. Certainly that is not too much to ask for this Christmas.

Originally posted here:
Another year of climate change, genetics and Irish scientific ambition - The Irish Times

Biodiversity the variation in all living organisms is one of Africas richest assets. As a result, its genetic material is coveted by scientists, biotechnology companies and research institutes globally. For decades, there has been a flow of data and biosamples from the African continent to the global north. This has often been in the absence of legitimate participant consent, community engagement or data or material transfer agreements.

Biopiracy the act of directly or indirectly taking undue advantage of research participants and communities in global health research has a long and contentious history in Africa. A recent case occurred during the West African Ebola outbreak between 2014 and 2016 when thousands of biological specimens left the continent without consent. Very often there is minimal benefit sharing.

The issue has been in the news again in South Africa. Accusations have been levelled against the Wellcome Sanger Institute in the UK for allegedly attempting to commercialise data obtained from various African universities. This has reignited questions around models of consent in research, donor rights, biopiracy and genomic sovereignty.

The latest revelations show that legislation as well as academic research governance bodies have failed to adequately safeguard the rights of vulnerable participants in genomics research.

One missing piece of the puzzle is the limited empirical data on the views of people whose biosamples are taken in the name of research. This would include issues of ownership, future use, export, benefit-sharing and commercialisation.

In 2011 and 2012 we surveyed participants to better understand their views. We recruited participants who had experience with research, the consent process and use of biological samples. They were engaged in studies at academic research units attached to public hospitals and private research centres.

Our findings remain relevant today as many of the issues raised by the people we spoke to have still not been addressed.

Our study was conducted over a 10 month period from September 2011 to June 2012. We sampled 200 participants in the Western Cape and Gauteng provinces in South Africa. Participants who had already consented to use of their blood for research were asked several questions including the following: how they felt about their samples being stored for future use and about them being sent abroad to foreign countries, as well as the possibility of future commercialisation.

Most participants were supportive of research. But many expressed concerns about export of their blood samples and data out of South Africa.

For their part, researchers viewed the biosamples as donations. But participants believed they had ownership rights and were keen on benefit sharing. Almost half of the participants were not in favour of broad consent delegated to a research ethics committee. Their preference was to be contacted again for consent in the future.

The legitimacy of using broad consent models for genomic research and biobanking occupies a contested space among bioethicists and researchers globally. Broad consent allows researchers to use biosamples and data indefinitely for future research.

Usually, with broad consent, future research must be approved by a Research Ethics Committee (a diverse group of experts from different research, medical, legal and ethics disciplines) and it is then not necessary to contact donors and ask for their permission to conduct research with their samples or data again.

But this type of consent is particularly contentious in resource depleted countries. This is because research participants often dont understand the complex scientific jargon used in consent documents or processes, especially where use of their samples or data in the future is concerned. This includes commercialisation.

Strong privacy protection legislation and other similar laws require specific consent. This means that individual participants need to consent to use of their data in a specific project or disease category. This makes it challenging to understand how broad consent (delegated to a research ethics committee) for unspecified future use can be legally obtained in research.

This is particularly concerning where future commercialisation may be included in broad consent models without being explicitly discussed with participants. The language used to explain commercialisation is often vague and not fully comprehensible by vulnerable populations.

South Africa also has protocols in place. For example, clear, explicit, voluntary informed consent is required for all use of data and samples belonging to research participants. If data or samples are to be transferred to other researchers in South Africa or abroad, participants ought to be aware of this and can then consent or decline. However, this is not always what happens.

In addition, if data is to be shared with another institution, a data transfer agreement or material transfer agreement must be signed prior to the transfer. This too does not always happen.

South Africa needs to up its game and reform governance around research ethics. This is particularly necessary in the context of international collaborative research. Good governance needs to incorporate transparency, fairness and honesty.

Research ethics committees and researchers need to ensure that data transfer agreements or material transfer agreements are in place prior to sharing of samples or data.

More importantly, community representatives on research ethics committees should be empowered to review consent documents to establish if appropriate language is used to explain commercialisation and data or sample sharing.

A tiered consent model gives participants choice in terms of how their data or samples could be used in the future. This happens when participants choose what they agree to in the consent document. It also allows for specific choices to be voiced on benefit sharing for participants or their respective communities.

In addition, authentic community engagement with co-creation of knowledge production and benefit sharing is essential to ensure equity in global research.

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Africa's genetic material is still being misused - The Conversation Africa

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to tucatinib, in combination with trastuzumab and capecitabine, for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. The positive topline results of the pivotal HER2CLIMB clinical trial were announced in October 2019, and additional data were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) on December 11, 2019 and were simultaneously published in the New England Journal of Medicine (NEJM). Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

The FDAs Breakthrough Therapy process is intended to expedite the development and review of promising drug candidates intended for serious or life-threatening conditions. Designation is based upon preliminary clinical evidence of the potential for substantial improvement over existing therapies on one or more clinically significant endpoints.

The addition of tucatinib to the commonly used combination of trastuzumab and capecitabine demonstrated superior activity compared to trastuzumab and capecitabine alone in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases, said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. The decision by the FDA to grant Breakthrough Therapy designation to tucatinib recognizes the urgent need for new medicines that can impact the lives of those with HER2-positive metastatic breast cancer. We intend to submit a New Drug Application to the FDA and an MAA to the EMA by the first quarter 2020, with the goal of making tucatinib available to patients in this setting as soon as possible.

This Breakthrough Therapy designation was based on data from the pivotal HER2CLIMB clinical trial, which compared tucatinib in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer. Patients had previously received trastuzumab, pertuzumab and ado-trastuzumab emtansine (T-DM1). Patients had received a median of four prior lines of therapy overall and three in the metastatic setting. Forty-seven percent of the patients enrolled in the trial had brain metastases at the time of enrollment.

Data presented at SABCS and published in NEJM include the primary endpoint of progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. The primary endpoint of PFS showed that the addition of tucatinib was superior to trastuzumab and capecitabine alone, with a 46 percent reduction in the risk of disease progression or death (hazard ratio (HR)=0.54 (95% Confidence Interval (CI): 0.42, 0.71); p<0.00001). The trial met the two key secondary endpoints at interim analysis. The tucatinib arm demonstrated an improvement in overall survival, with a 34 percent reduction in the risk of death (HR=0.66 [95% CI: 0.50, 0.88]; p=0.0048), compared to the control arm. For patients with brain metastases at baseline, the tucatinib arm also demonstrated superior PFS, with a 52 percent reduction in the risk of disease progression or death, compared to the control arm (HR=0.48 [95% CI: 0.34, 0.69]; p<0.00001).

Tucatinib in combination with trastuzumab and capecitabine was generally well tolerated. The most common adverse events occurring in more than 20 percent of patients in the tucatinib arm vs. the control arm included diarrhea, palmar-plantar erythrodysaesthesia syndrome (PPE), nausea, fatigue, and vomiting. Discontinuation of tucatinib and placebo due to adverse events was 5.7 percent in the tucatinib arm and 3.0 percent in the control arm. Greater than or equal to Grade 3 diarrhea was seen in 12.9 percent of the patients in the tucatinib arm vs. 8.6 percent in the control arm. Antidiarrheal prophylaxis was not required per protocol. Antidiarrheals were used in less than half of all cycles where diarrhea was reported. In both treatment arms, when used, the duration of antidiarrheal treatment was short (median of 3 days/cycle). Greater than or equal to Grade 3 aspartate aminotransferase (AST) was seen in 4.5 percent of the patients in the tucatinib arm vs. 0.5 percent in the control arm, and alanine aminotransferase (ALT) elevation in 5.4 percent vs. 0.5 percent, respectively. Discontinuations due to liver transaminase elevations were infrequent in both arms (ALT: 1.0 vs. 0.5 percent; AST: 0.7 vs. 0.5 percent).

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline and confirmed objective response rate. Safety data were evaluated throughout the study.

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1,2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is progression-free survival per RECIST criteria. Secondary endpoints include overall survival, objective response rate and duration of response. The trial is being conducted in North America and is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST criteria. Progression-free survival, duration of response, overall survival and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

About Seattle Genetics

Seattle Genetics, Inc. is an emerging multi-product, global biotechnology company that develops and commercializes transformative therapies targeting cancer to make a meaningful difference in peoples lives. ADCETRIS (brentuximab vedotin) utilizes the companys industry-leading antibody-drug conjugate (ADC) technology and is currently approved for the treatment of multiple CD30-expressing lymphomas. Beyond ADCETRIS, the company has a late-stage pipeline including enfortumab vedotin for metastatic urothelial cancer, currently being reviewed for approval by the FDA, and tisotumab vedotin in clinical trials for metastatic cervical cancer, which utilize our proprietary ADC technology. In addition, tucatinib, a small molecule tyrosine kinase inhibitor, is in late-stage development for HER2-positive metastatic breast cancer and in clinical development for metastatic colorectal cancer. We are also leveraging our expertise in empowered antibodies to build a portfolio of proprietary immuno-oncology agents in clinical trials targeting hematologic malignancies and solid tumors. The company is headquartered in Bothell, Washington, and has a European office in Switzerland. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

Forward Looking Statements

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of tucatinib, including its possible efficacy, safety and therapeutic uses; anticipated development activities including ongoing and future clinical trials; and intended regulatory actions, including the plan to submit an NDA to the FDA and a MAA to the EMA by the first quarter of 2020. 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 difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, the possibility of disappointing results in ongoing or future clinical trials despite earlier promising clinical results, the possibility of delays in the submission of an NDA to the FDA and a MAA to the EMA, the possibility that data from the HER2CLIMB trial may not be sufficient to support approval of tucatinib, the possibility of adverse regulatory action. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the companys Quarterly Report on Form 10-Q for the quarter ended September 30, 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.

References:

1. American Cancer Society, Cancer Facts and Figures 2018-2019.

2. Loibl S, Gianni L (2017). HER2-positive breast cancer. The Lancet 389(10087): 2415-29.

3. Slamon D, Clark G, Wong S, et al. (1987). Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785): 177-82.

4. American Cancer Society (ACS) (2018). Breast cancer HER2 status. Accessed: December 10, 2018.

5. Kennecke H, Yerushalmi R, Woods R, et al. (2010). Metastatic Behavior of Breast Cancer Subtypes. Journal of Clinical Oncology 28(20): 3271-7.

6. Berman AT, Thukral AD, Hwang W-T, et al. (2013). Incidence and Patterns of Distant Metastases for Patients With Early-Stage Breast Cancer After Breast Conservation Treatment. Clinical Breast Cancer 13(2): 88-94.

7. Duchnowska R, Loibl S, Jassem J (2018). Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treatment Reviews 67: 71-7.

8. Verma S, Miles D, Gianni L, et al. (2012). Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 367(19): 1783-91.

9. Geyer CE, Forster J, Lindquist D, et al. (2006). Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 355(26): 2733-43.

10. Blackwell KL, Burstein HJ, Storniolo AM, et al. (2012). Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study. Journal of Clinical Oncology 30(21): 2585-92.

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Seattle Genetics Announces U.S. FDA Grants Breakthrough Therapy Designation for Tucatinib in Locally Advanced or Metastatic HER2-Positive Breast...

Diversity starts at the gene level

Natural killer (NK) cells are immune cells with potent antiviral and antitumor activities. These cells express several germline-encoded inhibitory receptors (KIRs) that prevent NK cells from killing healthy cells but enable the targeting of infected and transformed cells. Using various imaging techniques and functional assays, Kennedy et al. investigated the effects of genetic diversity in KIR-encoding genes on receptor organization and activity. They found that KIRs encoded by distinct genes were present at varying abundances and in clusters of varying sizes, which led to differences in downstream signaling that affected NK cell function. Together, these data suggest that genetic diversity in KIR-encoding genes affects receptor organization, signaling, and functional outcomes.

Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs encoded by different genes and alleles were organized differently at the surface of primary human NK cells. KIRs that were found at low abundance assembled into smaller clusters than those formed by KIRs that were more highly abundant, and at low abundance, there was a greater proportion of KIRs in clusters. Upon receptor triggering, a structured interface called the immune synapse assembles, which facilitates signal integration and controls NK cell responses. Here, triggering of low-abundance receptors resulted in less phosphorylation of the downstream phosphatase SHP-1 but more phosphorylation of the adaptor protein Crk than did triggering of high-abundance receptors. In cells with greater KIR abundance, SHP-1 dephosphorylated Crk, which potentiated NK cell spreading during activation. Thus, genetic variation modulates both the abundance and nanoscale organization of inhibitory KIRs. That is, as well as the number of receptors at the cell surface varying with genotype, the way in which these receptors are organized in the membrane also varies. Essentially, a change in the average surface abundance of a protein at the cell surface is a coarse descriptor entwined with changes in local nanoscale clustering. Together, our data indicate that genetic diversity in inhibitory KIRs affects membrane-proximal signaling and, unexpectedly, the formation of activating immune synapses.

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Genetic diversity affects the nanoscale membrane organization and signaling of natural killer cell receptors - Science

Over the past few years most Americans have been more and more curious about their family trees thanks to kits like 23 and Me and Ancestry.com. But did you know your DNA could be used to solve cold cases, convict people whove committed violent crimes, and even exonerate the wrongfully accused?One local genealogist explains why this seeming harmless gift could unlock a world of answered questions for law enforcement.Closure, is the driving force behind genetic genealogists Shera LaPoint.To be able to give that gift to some one has changed my life. Its the most rewarding thing Ive ever done.

Throughout the years she has closed dozens of cold cases thanks familial DNA but the popularity of DNA testing groups like 23 and Me, have a lesser known option that can be beneficial to law enforcement.

As a tester you have a right to decide what information you want to put out there and who its shared with.

Users can also opt into sharing their DNA with officers helping them in several ways, thanks to new technology.

By uploading your DNA you never know who you will be actually helping. We can take these criminals off the streets, we can exonerate innocent people, we can identify John and Jane Does, and also the fallen military who are unnamed, said LaPoint.They can use my DNA or someone I manage that has agreed to opt in, to help capture a dangerous individuals, then I really dont have a problem, says Mark Richard.

Mark Richard, supports opting into sharing DNA with law enforcement because he says it can close dark chapters in peoples lives.

Richard adds, sometimes these are unsolved crimes where families can not get closure. People dont know what happened from an incident you know someone got murdered or raped and people never know who did it. Then these cases go cold because they didnt have the DNA back then so this is giving families an opportunity for closure.Then you give a DNA kit as a Christmas gift, think about going the extra mile and giving a little bit extra by uploading your DNA. Opting into law enforcement use, and lets make a difference in this world, said LaPoint.Aside from working on cold cases, Shera also uses genetic geology to connect adoptees with their parents . For more information about Shera and all her works, click here.

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Genetic Genealogy Helping Law Enforcement Close Cold Cases and More - News15 | Lafayette, LA - FOX 15

A trip to the theater, museum or art gallery could help you live longer. And the more often you get that culture fix the better, a new study suggests.

Researchers from University College London (UCL) found that people who engaged in the arts more frequently -- every few months or more -- had a 31% lower risk of dying early when compared to those who didn't. Even going to the theater or museum once or twice a year was linked with a 14% lower risk.

They looked at data given by more than 6,000 adults in England age 50 years and older, who were taking part in a wider study on aging.

How often an individual engaged in art activities, which also included exhibitions, concerts and opera but not cinema, was measured at the start of the study in 2004 to 2005. Participants were then followed up for an average of 12 years, during which time deaths were recorded using data from the UK's National Health Service (NHS.)

Why?

The study looked at a range of economic, health and social factors to try and explain why there is a link between "arts engagement" and living longer, although as an observational study it can't establish cause. Part of the reason, the study said, comes down to social and economic differences among those who go and don't go to museums, exhibitions and art galleries.

Wealth, they found, explained about 9% of the association. Cognitive differences, social and civic engagement, mental health, mobility and disability and deprivation also played a role. Things like free time and occupational status made no material difference, said Fancourt.

"Part of the association is attributable to differences in socioeconomic status among those who do and do not engage in the arts, which aligns with research that suggests engagement in cultural activities is socially patterned," the study said.

However, said Fancourt, "over half the association is independent of all the factors we identified that could explain the link."

She said that engaging with the arts can act as a buffer against stress and build creativity that allows people to adapt to changing circumstances. It also helps people build social capital -- accessing emotional support and information that helps people age more successfully.

"We also thought that a greater sense of purpose could play a role," she said. "If this (study) is added to the larger body of evidence, we are getting an increasingly rich picture on how arts can benefit health and it's not about one single outcome. It can have wide ranging benefits and support healthier lives lived longer."

How do you fall in love with art?

"Clinicians who read the paper might recognize the value of the arts, but will also wonder how engagement with culture and the arts could influence longevity," the editorial said.

"There is already much published work about the positive neurophysiological changes induced by activities, including the arts, which enable 'deep play' or 'flow.' However, as the authors note, further research is needed into the possible mechanisms that link cultural engagement with longer life."

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Visit museums or art galleries and you may live longer, new research suggests - CNN