StemCell Therapy

3D illustration of cells releasing exosomes

Scientists have developed a new gene-therapy technique by transforming human cells into mass producers of tiny nano-sized particles full of genetic material that has the potential to reverse disease processes.

Though the research was intended as a proof of concept, the experimental therapy slowed tumor growth and prolonged survival in mice with gliomas, which constitute about 80 percent of malignant brain tumors in humans.

The technique takes advantage of exosomes, fluid-filled sacs that cells release as a way to communicate with other cells.

While exosomes are gaining ground as biologically friendly carriers of therapeutic materials because there are a lot of them and they dont prompt an immune response the trick with gene therapy is finding a way to fit those comparatively large genetic instructions inside their tiny bodies on a scale that will have a therapeutic effect.

This new method relies on patented technology that prompts donated human cells such as adult stem cells to spit out millions of exosomes that, after being collected and purified, function as nanocarriers containing a drug. When they are injected into the bloodstream, they know exactly where in the body to find their target even if its in the brain.

Think of them like Christmas gifts: The gift is inside a wrapped container that is postage paid and ready to go, said senior study author L. James Lee, professor emeritus of chemical and biomolecular engineering at The Ohio State University.

And they are gifts that keep on giving, Lee noted: This is a Mother Nature-induced therapeutic nanoparticle.

The study is published in the journal Nature Biomedical Engineering.

In 2017, Lee and colleagues made waves with news of a regenerative medicine discovery called tissue nanotransfection (TNT). The technique uses a nanotechnology-based chip to deliver biological cargo directly into skin, an action that converts adult cells into any cell type of interest for treatment within a patients own body.

By looking further into the mechanism behind TNTs success, scientists in Lees lab discovered that exosomes were the secret to delivering regenerative goods to tissue far below the skins surface.

The technology was adapted in this study into a technique first author Zhaogang Yang, a former Ohio State postdoctoral researcher now at the University of Texas Southwestern Medical Center, termed cellular nanoporation.

The scientists placed about 1 million donated cells (such as mesenchymal cells collected from human fat) on a nano-engineered silicon wafer and used an electrical stimulus to inject synthetic DNA into the donor cells. As a result of this DNA force-feeding, as Lee described it, the cells need to eject unwanted material as part of DNA transcribed messenger RNA and repair holes that have been poked in their membranes.

They kill two birds with one stone: They fix the leakage to the cell membrane and dump the garbage out, Lee said. The garbage bag they throw out is the exosome. Whats expelled from the cell is our drug.

The electrical stimulation had a bonus effect of a thousand-fold increase of therapeutic genes in a large number of exosomes released by the cells, a sign that the technology is scalable to produce enough nanoparticles for use in humans.

Essential to any gene therapy, of course, is knowing what genes need to be delivered to fix a medical problem. For this work, the researchers chose to test the results on glioma brain tumors by delivering a gene called PTEN, a cancer-suppressor gene. Mutations of PTEN that turn off that suppression role can allow cancer cells to grow unchecked.

For Lee, founder of Ohio States Center for Affordable Nanoengineering of Polymeric Biomedical Devices, producing the gene is the easy part. The synthetic DNA force-fed to donor cells is copied into a new molecule consisting of messenger RNA, which contains the instructions needed to produce a specific protein. Each exosome bubble containing messenger RNA is transformed into a nanoparticle ready for transport, with no blood-brain barrier to worry about.

The advantage of this is there is no toxicity, nothing to provoke an immune response, said Lee, also a member of Ohio States Comprehensive Cancer Center. Exosomes go almost everywhere in the body, including passing the blood-brain barrier. Most drugs cant go to the brain.

We dont want the exosomes to go to the wrong place. Theyre programmed not only to kill cancer cells, but to know where to go to find the cancer cells. You dont want to kill the good guys.

The testing in mice showed the labeled exosomes were far more likely to travel to the brain tumors and slow their growth compared to substances used as controls.

Because of exosomes safe access to the brain, Lee said, this drug-delivery system has promise for future applications in neurological diseases such as Alzheimers and Parkinsons disease.

Hopefully, one day this can be used for medical needs, Lee said. Weve provided the method. If somebody knows what kind of gene combination can cure a certain disease but they need a therapy, here it is.

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A New Gene Therapy Strategy, Courtesy of Mother Nature - Global Health News Wire

Hong Kong-based Food Tech accelerator Brinc just announced their latest cohort and there are some inspiring startups working to solve some of the worlds more pressing issues including malnutrition, the rise of diabetes and the environmental footprint of livestock farming. From food safety to cleaner protein to increased nutrient density, we round up the five most impressive and sustainably-minded companies in the Fall 2019 batch.

Founding date: 2018

Founding Team: Carrie Chan & Mario Chin

Headquarters: Hong Kong

Sustainable Food Mission: Avant Meats is a food tech startup cultivating fish and seafood products using cellular technology and tissue engineering of a small sample of swim bladder and fish cells under lab conditions. Demand for seafood delicacies in traditional Chinese cuisine has seriously threatened some fish species and marine ecosystems, and the industry is mired with traceability issues. Set to debut their first fish maw product in 2023, the company hopes to tackle both issues to help Asian seafood eaters consume sustainably with knowledge of how their seafood has been produced.

Founding date: 2016

Founding Team: Prakash Ramadass, Monisha Reddy, Swaminathan Detchanamurthy, Suganya Baskaran

Headquarters: India

Sustainable Food Mission: Seagrass Tech has developed a cultivation and harvesting technology platform that uses seawater and non-arable tsunami affected land to grow marine microalgae, which can be used as a natural colourant in F&B, pharmaceutical and cosmetic products while capturing carbon dioxide.

Founding date: 2019

Founding Team: Sofia Giampaoli

Headquarters: Argentina

Sustainable Food Mission: Cell Farm is the first cultured meat startup in Latin America, and are developing a cow stem cell bank to provide high-quality, efficient and certified starter materials for the cultured beef industry. They are currently standardising their biotech process to produce meat from animal stem cells by performing a non-invasive microbiopsy from different cow species, and then differentiating those cells into muscle and fat tissue that mimics the taste and texture of different types of beef products.

Founding Date: 2019

Founding Team: Luciano Bueno

Headquarters: United States

Sustainable Mission: The only non food startup in our roundup, Galy is producing cotton in the lab from cells, rather than from plants. With their biomaterial technology, Galys cotton is not only grown 10 times faster and of a higher quality than conventionally produced cotton, but also requires 78% less water, 81% less land and generates 80% fewer gas emissions. Currently, Galy is selling their cellular cotton yarns to brands and the textile industry.

Founding date: 2016

FouFounding Team: Kushal Aradhya

Headquarters: India

Sustainable Food Mission: Naka Foods has developed a vegetarian microalgae-based convenient cereal bar, the 4PM Bar, which is made with oats, cashews and spirulina and enriched with probiotics. They are looking to create more nutrient-dense food items with microalgae technology, including a plant-based chicken product that is currently under the R&D process.

Lead image courtesy of Shutterstock.

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5 Inspiring Startups Looking To Change The World From Cell-Based Cotton To Micro-Algae Chicken - Green Queen Media

(Reuters Health) - Young adults who have had knee injuries are much more likely than uninjured peers to develop arthritis in the knee by middle age, especially if they have broken bones or torn connective tissue, a recent study suggests.

Researchers followed almost 150,000 adults ages 25 to 34, including about 5,200 with a history of knee injuries, for almost two decades. Compared to people who never had knee injuries, those who did were nearly six times as likely to develop knee osteoarthritis during the first 11 years of follow-up, with more than triple the risk over the next eight years.

Injuries that occur inside the knee joint, for example in the meniscus or cruciate ligament, may alter the biomechanical loading patterns in the knee, said study leader Barbara Snoeker, of Lund University in Sweden.

Such injuries may lead to an imbalance in force transmissions inside the knee joint, consequently overloading the joint cartilage and leading to increased risk of developing osteoarthritis, compared to injuries that mainly affect the outside of the knee joint, such as contusions, Snoeker said by email.

Osteoarthritis often affects the large weight-bearing joints and can eventually lead to the need for total joint replacement, the researchers note in the British Journal of Sports Medicine.

Known risk factors include being overweight, older, female or having a job that puts a lot of stress on the joints, the study team notes. While a history of knee injuries is also a known risk factor, research to date hasnt offered a clear picture of whether certain types of injuries might be more likely to lead to osteoarthritis.

Two-thirds of the people in the study with knee injuries were male. After 19 years of follow-up, 422 people with knee injuries, or 11.3%, developed knee osteoarthritis. So did 2,854, or 4%, of people without knee injuries.

Most often, injuries involved multiple structures of the knee; this accounted for 21% of participant knee injuries. The second most common type of injury was cuts and contusions, at 18%, followed by cartilage or other tissue tears at 17%.

Cruciate ligament injuries, or damage to the tissue connecting the thighbone to the shinbone, were associated with a 19.6% greater risk of knee osteoarthritis, the study also found. Meniscal tears, or damage to cartilage connecting the same two bones, were associated with a 10.5% greater risk of osteoarthritis. Fractures of the shinbone where it meets the knee, or of the kneecap, were associated with a 6.6% greater risk.

Injuries involving multiple structures in the knee may have been underreported, leading researchers to underestimate the risk associated with these types of injuries, Jonas Bloch Thorlund, a professor of musculoskeletal health at the University of Southern Denmark, in Odense, who wasnt involved in the study, said by email.

Another limitation is that researchers didnt look at patients body mass index (BMI), so they couldnt tell whether differences in weight might explain patients risk of osteoarthritis, said Dr. Kyle Hammond of the Emory Sports Medicine Center in Atlanta.

What happens after knee injuries can also influence the risk of osteoarthritis down the line, Hammond, who wasnt involved in the study, said by email.

Counseling a patient on how to safely and consistently return to a positive fitness program ensures that they will maintain flexibility and strength, as well as keeping their weight at their ideal body weight, Hammond advised.

Rehab matters regardless of what other treatments patients receive, said Adam Culvenor, a sports and exercise medicine researcher at La Trobe University in Bundoora, Australia, who wasnt involved in the study.

Once these injuries occur, optimally managing them with an intense and progressive period of rehabilitation under the guidance of a physical therapist (irrespective of the decision to have surgery or not) to strengthen the muscles around the knee to facilitate a return to function and physical activity is likely to reduce the risk of osteoarthritis and persistent symptoms longer-term, Culvenor said by email.

SOURCE: bit.ly/2MhjRto British Journal of Sports Medicine, online December 11, 2019.

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Knee injuries in early adulthood may hasten arthritis - Reuters

FRUITA,Co.(KKCO)-- Dr.Rooks rheumatologist from the Arthritis Center of Western Colorado at Family Health West stopped by and discussed the difference between Spondyloarthritis and Inflammatory arthritis.

Doctors see a lot of patients with Spondyloarthritis on the Western slope especially among young adults.

Symptoms of Spondyloarthritis are stiffness when you wake up, and inflammation in the spine, hips, and knees.

Inflammatory arthritis is the most common type of arthritis. Symptoms include new joint or tendon pain, swelling, stiffness that lasts more than an hour in the morning without prior injury.

Inflammatory arthritis is actually a systemic disease of the immune system that, if not treated appropriately, can lead to joint and tendon damage, deformities, and contribute to heart attacks, strokes, and more.

If you have more questions on arthritis visit their website http://www.ac-wc.com.

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Family Health West's Dr.Rook Discusses Spondyloarthritis and Inflammatory Arthritis - KKCO-TV

It took 16 years after Ethan Nelsons arthritis diagnosis until he met someone who shared his condition.

There is definitely this generation where if you get diagnosed, you are alone, Nelson said. You dont have anyone.

Nelson, now 22 years old and a junior at Brigham Young University, was diagnosed with systemic juvenile idiopathic arthritis when he was 4 years old. He spent the last two years volunteering for arthritis-related causes and helping to build a network of young adults who share the same condition.

He was honored Dec. 7 in Salt Lake City at the Jingle Bell Run, a 5K that benefits the Arthritis Foundation.

The run honored six people, which also included Kendall Pogue, who is also a BYU student, and Spencer Hood, who, along with Nelson, had tried to connect young adults with arthritis.

Hood first connected Nelson with the Jingle Bell Run two years ago. This year, Nelson led a team and raised $530 of his groups $810 total.

He is a really great guy, said Debbie Jordan, the executive director of the Arthritis Foundation of Utah. You have to think about what it is like for a college kid to get up at 4 a.m. in the morning and help us out.

Jordan said the honorees are volunteers who have done more than the average for the foundation. She said theres typically about 40 BYU students who come to help out at the run.

The young adult volunteers, she said, show children with arthritis that they can still achieve their goals.

I think it gives them a lot of hope, Jordan said.

Its not the first time Nelson has been involved with raising awareness and funding for arthritis. He was the literal poster boy for the National Arthritis Foundation when he was about 5 years old, showing the effects that his treatment at the time, the steroid prednisone, has on the body.

Since then, hes had two hip replacements one when he was 13, the other at 16 and had surgery on his ankle.

He was on the tail end of a generation that exclusively used prednisone, which has been mostly replaced with biologic treatments and IV infusions for young patients. The last two years have been rough as he tried to find a medicine his body responded well to. After trying five different treatments, hes doing well again.

I feel like 100% normal, Nelson said. I can walk without pain.

Hes volunteered at Camp Kids Out to Defeat Arthritis, also known as Camp KODA. While there, he advocates for campers to become independent in order to prevent flare ups and joint damage.

I know these kids very personally now and I dont want my mistakes to rub off on them in the future, Nelson said. So it is like, dont let your arthritis hold you back, dont take advantage of it and stay on top of things.

The Arthritis Foundation estimates that one in four adults have arthritis, which includes 400,000 adults and 3,000 children in Utah.

Nelson said that while someone in their 20s is just as likely to be diagnosed as someone who is 60, young adults often dont talk about having arthritis.

It is so much easier to conceal, to hide, than cancer, and so I feel like people have the opportunity to hide it and so they do from others because they dont want to feel like the odd one out, he said.

While he feels the Arthritis Foundation does well with reaching young children and older adults, Nelson said young adults can be left out. He and Hood are trying to find more young adults who have arthritis for their group, Utah YA Champions. Nelson is also working to create a student association at BYU for students with arthritis.

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BYU student connecting 'lost generation' honored by Arthritis Foundation - Daily Herald

BACKGROUND/OBJECTIVE:

Rheumatoid arthritis (RA) is a complex disease that may require treatment with one or several disease-modifying antirheumatic drugs (DMARDs). Many DMARDs have potential teratogenic effects or are newer agents with limited safety data in pregnancy. This study evaluated 20 common RA medications and the rate of contraceptive prescribing and counseling patterns in women with RA of childbearing ability.

This was an observational study of women with RA and childbearing ability aged 18 to 44 years who were seen at an academic rheumatology clinic from April 1, 2014, to March 31, 2016. Descriptive statistics and univariate logistic regression were used for analysis.

One hundred fifty women were included in the analysis. The majority of patients were taking methotrexate (55.3%), followed by chronic prednisone (31.3%) and hydroxychloroquine (28.7%). A documented method of contraception was noted in 64/150 (42.7%). For women on contraception, most used combined oral contraceptives (31/64, 48.4%) or levonorgestrel intrauterine device (10/64, 15.6%). Of the 86 patients not on contraception, 19 (22.1%) received counseling regarding a pregnancy plan.

Most women with RA of childbearing age and ability were not using contraception. Among these patients, only a minority prescribed DMARD therapy had documented pregnancy or contraceptive counseling. Women with RA who were prescribed with a DMARD should discuss the use of effective contraception with their provider if sexually active and not desiring pregnancy or wanting to avoid potential teratogenic effects. Potential strategies are discussed to improve healthcare delivery to this population in hopes of avoiding unintended pregnancy and potential teratogenic effects of RA medications.

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Contraceptive Use in Women of Childbearing Ability With Rheumatoid Arthritis - DocWire News

Lets start with what to eat and the foods to avoid eating. What follows will likely sound familiar to aficionados of a Mediterranean-style diet: a plant-based diet focused on fruits and vegetables, whole grains, and cold-water fish and plants like soybeans and flax seeds that contain omega-3 fatty acids.

A Mediterranean-style diet is rich in micronutrients like magnesium, vitamin E and selenium that have anti-inflammatory effects, and its high-fiber content fosters lower levels of two potent inflammatory substances, IL-6 and TNF-alpha.

Dr. Frank Hu, professor of nutrition and epidemiology at the Harvard T.H. Chan School of Public Health, strongly recommends limiting or eliminating consumption of foods known to have a pro-inflammatory effect. These include all refined carbohydrates like white bread, white rice and pastries; sugar-sweetened beverages; deep-fried foods; and red meat and processed meats. They are the very same foods with well-established links to obesity (itself a risk factor for inflammation), heart disease and Type 2 diabetes.

In their stead, Dr. Hu recommends frequent consumption of foods known to have an anti-inflammatory effect. They include green leafy vegetables like spinach, kale and collards; fatty fish like salmon, mackerel, tuna and sardines; fruits like strawberries, blueberries, apples, grapes, oranges and cherries; nuts like almonds and walnuts; and olive oil. The recommended plant foods contain natural antioxidants and polyphenols, and the fish are rich in omega-3 fatty acids, all of which counter inflammation.

Coffee and tea also contain protective polyphenols, among other anti-inflammatory compounds.

The bottom line: the less processed your diet, the better.

At the same time, dont neglect regular exercise, which Dr. James Gray, cardiologist at the Scripps Center for Integrative Medicine, calls an excellent way to prevent inflammation. He recommends 30 to 45 minutes of aerobic exercise and 10 to 25 minutes of weight or resistance training at least four to five times a week.

Although exercise is pro-inflammatory while youre doing it, during the rest of the time it leaves you better off by reducing inflammation, and after all you live most of your life not exercising, Stephen Kritchevsky, professor of gerontology and geriatric medicine at Wake Forest School of Medicine, told me. Independent of any effect on weight, exercise has been shown to lower multiple pro-inflammatory molecules and cytokines.

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Tackling Inflammation to Fight Age-Related Ailments - The New York Times

Tens of thousands of people with conditions including arthritis, MS and psychosis have had their benefits cut or stopped after moving to a new Tory system.

Detailed statistics from the Department for Work and Pensions (DWP) show the reality of the 650,000 former Disability Living Allowance claimants who've lost out since 2013.

This week the Mirror reported how 46% of former DLA claimants lost money after moving to new benefit Personal Independence Payment (PIP).

In total, of the 1.424million DLA claimants reassessed for PIP by October 2019, 306,000 (22%) had their benefit cut, 293,000 (21%) had it stopped after an assessment, 58,000 (4%) had it stopped before assessment and 9,000 (1%) withdrew their claim.

In contrast 556,000 claimants (39%) saw their award rise and 200,000 (14%) had it unchanged.

But the DWP's detailed figures give a fascinating insight that show the real people behind the numbers.

The worst-hit were people with psychosis, 87,824 of whom either failed a PIP assessment entirely or had their money cut since 2013. By comparison, 63,395 saw their payment rise.

Some 86,042 arthritis sufferers had their PIP cut or stopped when they moved from DLA - while 68,256 saw it go up.

Scroll down for the full list of disabilities and how they are hit.

Epilepsy sufferers were also badly hit, with 23,640 losing some or all of their benefits compared to 12,344 who received more.

And 10,247 people with MS, 2,188 with AIDS and 960 with cystic fibrosis saw their money either cut or stopped.

Since 2013, even 69 double amputees have had their money cut when moving from DLA to PIP - while 161 saw their award go up.

Some groups were better off on average. 6,533 blind people saw payments cut or stopped but 23,098 saw them rise.

Likewise 39,020 people with learning difficulties lost out but 86,567 were better off.

These figures only relate to claimants who were already on the old DLA system when they claimed PIP.

And they do not include people who lost their benefits before an assessment, failed to attend an appointment, or withdrew their claim.

MS sufferer Rachel Taylor, from Halifax, West Yorkshire, told the Mirror she lost her adapted Motability car for around a year after her benefits were cut moving from DLA to PIP.

The 50-year-old mother-of-one and librarian uses a zimmer frame, walking stick and mobility scooter to get around.

But despite claiming DLA since 2002 she said she was awarded the lower rates of PIP after a 2016 assessment.

She waited around a year until, weeks before her appeal tribunal, she said she received a phone call saying she'd get the higher rate after all.

She told the Mirror: "I ended up taking several thousand pounds out of my pension pot.

"The stress has been immeasurable.

"I take pride in what Im able still able to do. But I now believe I was penalised for trying to keep my independence.

Ms Taylor still works part-time but said "I couldn't be more disabled."

She added: The local bus goes from a mile away but I cant walk to the end of my driveway.

"Theres no hope for me walking to catch a bus. I have a son that I have to get to school."

The DWP said Ms Taylor received 3,000 in arrears and a 2,000 transition payment for the Motability scheme.

A DWP spokesman added: Ms Taylor was granted enhanced level mobility Personal Independence Payment as soon as further evidence became available and a back payment of almost 3,000 was paid in arrears.

The DWP figures were condemned by charities earlier this week. Geoff Firmister of the Disability Benefits Consortium, which represents more than 100 groups, said: "These figures are very worrying and we suspect many of the decisions are wrong."

James Taylor of disability equality charity Scope said the figures were "extremely worrying". He added: Consistently high levels of PIP decisions are being overturned, which demonstrates the assessment is not fit for purpose."

A DWP spokesman said: The Government now spends more than 55 billion every year to support disabled people, more than at any time under the DLA system; with more people benefitting from support through PIP than did under DLA.

Most people get PIP after being reassessed from DLA.

"More than half have their award maintained or increased, with 29% receiving the highest level of support compared to 16% under DLA.

Here are the figures from the government.NOTE: Conditions are exactly as listed by the DWP. Figures only include reassessments from DLA to PIP.

Psychosis - More money: 63395 Less: 37916 Nothing: 49908

Psychoneurosis - More money: 48376 Less: 15408 Nothing: 35587

Learning Difficulties - More money: 86567 Less: 6697 Nothing: 32323

Arthritis - More money: 68256 Less: 65438 Nothing: 20604

Epilepsy - More money: 12344 Less: 8403 Nothing: 15237

Disease Of The Muscles Bones or Joints - More money: 31677 Less: 18572 Nothing: 12543

Back Pain - Other / Precise Diagnosis not Specified - More money: 31193 Less: 33449 Nothing: 8925

Neurological Diseases - More money: 22151 Less: 11918 Nothing: 7647

Heart Disease - More money: 9907 Less: 8829 Nothing: 4893

Chronic Pain Syndromes - More money: 11483 Less: 11254 Nothing: 4552

Hyperkinetic Syndrome - More money: 3737 Less: 1606 Nothing: 4452

Blindness - More money: 23098 Less: 2234 Nothing: 4299

Trauma to Limbs - More money: 10401 Less: 6658 Nothing: 4288

Personality Disorder - More money: 4755 Less: 3802 Nothing: 4165

Malignant Disease - More money: 5226 Less: 5431 Nothing: 3832

Cerebrovascular Disease - More money: 15472 Less: 7819 Nothing: 3631

Diabetes Mellitus - More money: 4560 Less: 3063 Nothing: 3426

Deafness - More money: 8864 Less: 2553 Nothing: 3396

Spondylosis - More money: 10520 Less: 10339 Nothing: 3087

Behavioral Disorder - More money: 3863 Less: 978 Nothing: 2811

Chest Disease - More money: 11761 Less: 8095 Nothing: 2632

Alcohol and Drug Abuse - More money: 4746 Less: 1900 Nothing: 2563

Major Trauma Other than Traumatic Paraplegia/Tetraplegia - More money: 4646 Less: 1727 Nothing: 2362

Multiple Sclerosis - More money: 11647 Less: 7970 Nothing: 2277

Unknown/Transfer from AA - More money: 21484 Less: 2813 Nothing: 2099

Asthma - More money: 3693 Less: 2614 Nothing: 1476

Renal Disorders - More money: 1984 Less: 2160 Nothing: 1417

Inflammatory Bowel Disease - More money: 979 Less: 1385 Nothing: 1184

Bowel and Stomach Disease - More money: 1535 Less: 1592 Nothing: 1182

Peripheral vascular Disease - More money: 2783 Less: 1968 Nothing: 1142

Skin Disease - More money: 1388 Less: 1069 Nothing: 1116

AIDS - More money: 552 Less: 1211 Nothing: 977

Multi System Disorders - More money: 2091 Less: 2156 Nothing: 928

Metabolic Disease - More money: 1809 Less: 1928 Nothing: 664

Terminally Ill - More money: 74 Less: 1292 Nothing: 641

Cystic Fibrosis - More money: 723 Less: 358 Nothing: 602

Blood Disorders - More money: 521 Less: 645 Nothing: 490

Dementia - More money: 2722 Less: 204 Nothing: 332

Parkinsons Disease - More money: 2353 Less: 1093 Nothing: 238

Cognitive disorder - other / precise diagnosis not specified - More money: 480 Less: 103 Nothing: 223

Haemophilia - More money: 113 Less: 164 Nothing: 141

Severely Mentally impaired - More money: 91 Less: 260 Nothing: 96

Haemodialysis - More money: 101 Less: 73 Nothing: 78

Traumatic Paraplegia/Tetraplegia - More money: 1104 Less: 687 Nothing: 61

Multiple Allergy Syndrome - More money: 60 Less: 44 Nothing: 45

Motor Neurone Disease - More money: 227 Less: 107 Nothing: 40

Infectious diseases - other / precise diagnosis not specified - More money: 56 Less: 37 Nothing: 39

Infectious diseases: Bacterial disease - Tuberculosis - More money: 37 Less: 37 Nothing: 25

Total Parenteral Nutrition - More money: 17 Less: 11 Nothing: 12

Infectious diseases: Bacterial disease - precise diagnosis not specified - More money: 15 Less: 10 Nothing: 10

Frailty - More money: 52 Less: 42 Nothing: 8

Deaf/Blind - More money: 153 Less: 13 Nothing: 5

Double Amputee - More money: 161 Less: 69 Nothing: ..

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DWP: How thousands with arthritis, MS and psychosis have lost benefits under new system - Mirror Online

NORTH CHICAGO, Ill., Dec. 18, 2019 /PRNewswire/ --AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the European Commission (EC) hasapproved RINVOQ (upadacitinib) for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs).6 RINVOQ is a once-daily selective and reversible JAK inhibitor and may be used as monotherapy or in combination with methotrexate (MTX).

"We are proud to offer this once-daily tablet as a new treatment option for patients with moderate to severe active rheumatoid arthritis," said Michael Severino, M.D., vice chairman and president, AbbVie. "As a company that has been dedicated to discovering and delivering transformative therapies for people living with rheumatic diseases for nearly two decades, RINVOQ expands our portfolio of treatment options for people living with this disease in Europe."

The EC approval of RINVOQ was supported by data from the global Phase 3 SELECT rheumatoid arthritis program, which evaluated nearly 4,400 patients with moderate to severe active rheumatoid arthritis in five pivotal studies: SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY.1-5 The studies include assessments of efficacy, safety and tolerability across a variety of patients, including those who failed or were intolerant to biologic DMARDs and who were nave or inadequate responders (IR) to MTX.1-5

"Nearly 3 million people in Europe are living with rheumatoid arthritis, the majority of whom don't reach remission and may be suffering from pain, fatigue, morning joint stiffness and flares," said Professor Ronald van Vollenhoven, M.D., Ph.D., Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands. "As seen in this large Phase 3 clinical trial program in rheumatoid arthritis, upadacitinib has the potential to significantly improve signs and symptoms of the disease and help more patients achieve remission or low disease activity."

Highlights From the Phase 3 SELECT Rheumatoid Arthritis Program

Across the SELECT Phase 3 studies, RINVOQ met all primary and ranked secondary endpoints.1-6 Overall, both low disease activity (assessed by DAS28-CRP3.2) and clinical remission rates (assessed by DAS28-CRP<2.6) were consistent across patient populations, with or without MTX.1-6

Highlights included:

More information on these trials can be found at http://www.clinicaltrials.gov (NCT02706847, NCT03086343, NCT02629159, NCT02706873, NCT02706951).

Earlier this year, RINVOQ received approval from the U.S. Food and Drug Administration (FDA) for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to MTX.9

About RINVOQ (upadacitinib) in the European Union6

RINVOQ (upadacitinib) is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate.

Important EU Safety Information6

RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.

Use in combination with other potent immunosuppressants is not recommended.

Serious and sometimes fatal infections have been reported in patients receiving upadacitinib. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis have been reported. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis have been reported with upadacitinib. Prior to initiating upadacitinib, consider the risks and benefits of treatment in patients with chronic or recurrent infection or with a history of a serious or opportunistic infection, in patients who have been exposed to TB or have resided or travelled in areas of endemic TB or endemic mycoses, and in patients with underlying conditions that may predispose them to infection. Upadacitinib therapy should be interrupted if a patient develops a serious or opportunistic infection. As there is a higher incidence of infections in patients 75 years of age, caution should be used when treating this population.

Patients should be screened for TB before starting upadacitinib therapy. Anti-TB therapy should be considered prior to initiation of upadacitinib in patients with previously untreated latent TB or in patients with risk factors for TB infection.

Viral reactivation, including cases of herpes zoster, were reported in clinical studies. Consider interruption of therapy if a patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during therapy with upadacitinib.

The use of live, attenuated vaccines during, or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunizations, including prophylactic zoster vaccinations, prior to initiating upadacitinib, in agreement with current immunization guidelines.

The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Immunomodulatory medicinal products may increase the risk of malignancies, including lymphoma. The clinical data are currently limited and long-term studies are ongoing. Malignancies, including non-melanoma skin cancer (NMSC), have been reported in patients treated with upadacitinib. Consider the risks and benefits of upadacitinib treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing upadacitinib therapy in patients who develop a malignancy.Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Absolute neutrophil count <1000 cells/mm3, absolute lymphocyte count <500cells/mm3, or haemoglobin levels <8g/dL were reported in <1% of patients in clinical trials. Treatment should not be initiated, or should be temporarily interrupted, in patients with these haematological abnormalities observed during routine patient management.

RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care.

Upadacitinib treatment was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo. If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, upadacitinib therapy should be interrupted until this diagnosis is excluded.

Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Upadacitinib should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient's risk for DVT/PE include older age, obesity, a medical history of DVT/PE, patients undergoing major surgery, and prolonged immobilisation. If clinical features of DVT/PE occur, upadacitinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.

The most commonly reported adverse drug reactions are upper respiratory tract infections (13.5%), nausea (3.5%), increased blood creatine phosphokinase (2.5%), and cough (2.2%). The most common serious adverse reactions were serious infections.

Please see the full SmPC for complete prescribing information at http://www.EMA.europa.eu.Globally, prescribing information varies; refer to the individual country product label for complete information

About HUMIRA in the European Union10

HUMIRA, in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs, including methotrexate, has been inadequate.

Important EU Safety Information10

HUMIRA is contraindicated in patients with active tuberculosis or other severe infections such as sepsis, and opportunistic infections and in patients with moderate to severe heart failure (NYHA class III/IV). It is also contraindicated in patients hypersensitive to the active substance or to any of the excipients; serious allergic reactions including anaphylaxis have been reported. The use of HUMIRA increases the risk of developing serious infections which may, in rare cases, be life-threatening. Rare cases of lymphoma and leukemia have been reported in patients treated with HUMIRA. On rare occasions, a severe type of cancer called hepatosplenic T-cell lymphoma has been observed and often results in death. A risk for the development of malignancies in patients treated with TNF-antagonists cannot be excluded. Rare cases of pancytopenia, aplastic anaemia, demyelinating disease, lupus, lupus-related conditions and Stevens-Johnson syndrome have been reported in patients treated with HUMIRA. The most frequently reported adverse events across all indications included respiratory infections, injection site reactions, headache and musculoskeletal pain.

Please see the full SmPC for complete prescribing information at http://www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie

AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience.In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us atwww.abbvie.com. Follow@abbvieon Twitter,Facebook,LinkedInorInstagram.

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2018 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References

SOURCE AbbVie

abbvie.com

Link:
AbbVie Receives European Commission Approval of RINVOQ (upadacitinib) for the Treatment of Adults with Moderate to Severe Active Rheumatoid Arthritis...

Osteoarthritis is a common and potentially debilitating condition. Its a degenerative joint disease (often called the wear-and-tear type) in which the smooth lining of cartilage becomes thinned and uneven, exposing the bone beneath.

Although osteoarthritis is tightly linked with aging, we now know there is more to it than age alone: genetics, weight, physical activity, and a number of other factors can conspire to make it more likely that someone will develop osteoarthritis while someone else wont. Osteoarthritis is the primary reason that more than a million joints (mostly hips and knees) are replaced each year in the US.

Treatments short of surgery can help but they dont always work well, dont cure the condition, and may be accompanied by side effects. Surgery is usually the last resort, reserved for people who have declining function, unrelenting pain, or both despite trying other treatments such as pain relieving, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, others) or naproxen (Aleve, others), or injections of steroids or hyaluronic acid (a type of lubricant). Nonmedication approaches can also help, such as loss of excess weight, physical therapy, or use of a cane or brace.

Steroid injections can quickly relieve inflammation in the joints, and the effects may last from several weeks to several months. Ive seen a number of patients who got significant relief from steroid injections every three or four months. But, a new report of one medical centers experience and a review of past research came to some concerning conclusions about joint injections for osteoarthritis of the hip or knee. These included:

Other side effects include a temporary increase in blood sugar, bleeding into the joint, and, quite rarely, infection. And, of course, the injection itself can be painful, although numbing medication is usually provided.

The authors suggest that doctors order x-rays before each injection and not perform injections if there is evidence of any of these complications or unexplained pain. However, its not clear how effective this approach would be.

The findings of this report regarding injections of steroids for knee and hip osteoarthritis are disappointing, especially for those who have not improved with other treatments.

Regarding the benefit of the injections, its important to keep in mind that even if the average benefit of a treatment is small, it does not mean that treatment is useless. Though temporary, some people do report significant improvement with steroid injections.

Its also not entirely clear that the problems described in this study are actually caused by the steroid injections. And, from my own experience, the rates of complications seem high to me. That said, a 2017 study did find that people getting steroid injections had more thinning of joint cartilage than those getting placebo injections.

In my own practice, Ill still offer a steroid injection for osteoarthritis, but only after carefully reviewing the potential risks and benefits. If it is not terribly helpful, I would not encourage repeated injections. On the other hand, if it works well, a limited number of injections (up to three or four per year is a common limit) may reduce pain and improve function and quality of life.

Restricting the injections to those who improve the most and limiting the number of injections each year may be a better strategy than eliminating steroid injections altogether, especially since the most serious side effects are quite rare.

Well need additional studies that examine the type, dosage, and frequency of steroid injections that might provide more benefit than risk. And well need better ways to predict who will improve the most. Until then, I think its important to keep an open mind about just how helpful and how safe steroid injections for osteoarthritis truly are.

Follow me on Twitter @RobShmerling

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A new look at steroid injections for knee and hip osteoarthritis - Harvard Health Blog - Harvard Health

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."

Continue reading here:
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.

Connect To Your Customers & Grow Your Business

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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

###

Original post:
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 competition by top Manufacturers:

Rheumatoid Arthritis and Lupus Treatments Market Outlook by Applications:

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

Marketing strategies in the report

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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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