FDA Approves Bavencio (avelumab) Plus Inlyta (axitinib) Combination for Patients with Advanced Renal Cell Carcinoma

In continuation of my update on axitinib

Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono in the US and Canada, and Pfizer Inc. (NYSE: PFE) today announced that the US Food and Drug Administration (FDA) has approved Bavencio (avelumab) in combination with Inlyta (axitinib) for the first-line treatment of patients with advanced renal cell carcinoma (RCC). This is the first FDA approval for an anti-PD-L1 therapy as part of a combination regimen for patients with advanced RCC. The approval of Bavencio in combination with Inlyta was based on positive results from the Phase III JAVELIN Renal 101 study (NCT02684006), in which the combination significantly improved median progression-free survival (PFS) compared with sunitinib by more than five months in the intent-to-treat (ITT) patient population (HR: 0.69 [95% CI: 0.56–0.84]; 2-sided p-value=0.0002; median PFS for Bavencio in combination with Inlyta: 13.8 months [95% CI: 11.1-NE]; sunitinib: 8.4 months [95% CI: 6.9-11.1]). The ITT population included patients regardless of PD-L1 expression and across IMDC (International Metastatic Renal Cell Carcinoma Database) prognostic risk groups (favorable 21%, intermediate 62% and poor 16%).

“As we look to continue to improve outcomes for people with advanced RCC, new treatment approaches have the potential to benefit patients,” said Robert J. Motzer, M.D., Jack and Dorothy Byrne Chair in Clinical Oncology, Memorial Sloan Kettering Cancer Center, New York, US, and principal investigator for JAVELIN Renal 101. “With today’s FDA approval of avelumab in combination with axitinib, we can now offer patients with advanced RCC a first-line treatment option that combines a PD-L1 immunotherapy with a well-known VEGFR TKI to provide a significant reduction in the risk of disease progression or death and doubling of the response rate compared with sunitinib.”

RCC is a type of cancer where PD-L1 expression may contribute to inhibition of the immune response against the tumor.2 It is also a highly vascular tumor, in which vascular endothelial growth factor (VEGF) plays a key role.3

“A kidney cancer diagnosis is life-changing for both patients and their loved ones, and having a treatment strategy for their disease quickly becomes a priority,” said Dena Battle, President, KCCure. “The approval of new treatments such as Bavencio in combination with Inlyta gives patients with advanced RCC much-needed options.”

There is a significant unmet need for first-line treatments that delay progression and have an acceptable safety profile. Approximately 20% to 30% of patients are first diagnosed with RCC at the advanced stage, and 30% of patients treated for an earlier stage go on to develop metastases.4,5 About half of patients living with advanced RCC do not go on to receive additional treatment after first-line therapy,6,7 for reasons that may include poor performance status or adverse events from their initial treatment.6,8,9

“Today’s approval of Bavencio in combination with Inlyta builds on Pfizer’s long heritage in bringing innovation to the RCC community with the hopes of making a significant and meaningful impact on the lives of patients,” said Andy Schmeltz, Global President, Pfizer Oncology. “For more than 12 years, Pfizer has led the field in its commitment to developing new treatments for patients with advanced kidney cancer.”

“With today’s FDA approval of Bavencio in combination with Inlyta, we feel privileged that we can offer patients with first-line advanced renal cell carcinoma a new treatment option,” said Rehan Verjee, President, EMD Serono, and Global Head of Innovative Medicine Franchises, Merck KGaA, Darmstadt, Germany.

In JAVELIN Renal 101, the objective response rate (ORR) was doubled in the ITT population with Bavencio in combination with Inlyta versus sunitinib (51.4% [95% CI: 46.6-56.1] vs. 25.7% [95% CI: 21.7-30.0]). With a median overall survival (OS) follow-up of 19 months, data for the trial’s other primary endpoint of OS were immature, with 27% of deaths in the ITT population, and the trial is continuing as planned. The most common adverse reactions (≥20%) were diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Serious adverse reactions occurred in 35% of patients receiving Bavencio in combination with Inlyta. The incidence of major adverse cardiovascular events (MACE) was higher with Bavencio in combination with Inlyta versus sunitinib.1 Findings from the study have been published in The New England Journal of Medicine.10

The European Medicines Agency (EMA) validated the Type II variation application for Bavencio in combination with Inlyta in advanced RCC in March 2019, and a supplemental application for Bavencio in combination with Inlyta in unresectable or metastatic RCC was submitted in Japan in January 2019.

The alliance is committed to providing patient access and reimbursement support through its CoverOne® program to patients who have been prescribed Bavencio. This program provides a spectrum of patient access and reimbursement support services intended to help US patients prescribed Bavencio receive appropriate access. CoverOne may be reached by phone at 844-8COVER1 (844-826-8371) or online at www.CoverOne.com.

Pfizer is committed to ensuring that patients who are prescribed Inlyta have access to this innovative therapy. Patients in the US have access to Pfizer Oncology Together™, which offers personalized support and financial assistance resources to help patients access their prescribed Pfizer Oncology medications. For more information, please call 1-877-744-5675 or visit PfizerOncologyTogether.com.

In an effort to streamline the patient enrollment process, EMD Serono and Pfizer have partnered to create a single enrollment form for the Bavencio and Inlyta combination for patients with advanced RCC that can be processed through both CoverOne and Pfizer Oncology Together. Each program will independently conduct the access and reimbursement activities for the product for which it is responsible.

Ref : https://en.wikipedia.org/wiki/Axitinib





FDA Approves Bavencio (avelumab) Plus Inlyta (axitinib) Combination for Patients with Advanced Renal Cell Carcinoma

Common Diabetes Drug Invokana (canagliflozin) May Also Shield Kidneys, Heart

In continuation of my update on canagliflozin

A common diabetes drug may also greatly reduce the odds for death from kidney failure and heart disease in diabetes patients with kidney disease, a new study finds.

  

The news on Invokana (canagliflozin) is important, experts say, because diabetes and kidney trouble so often go together.

"Diabetes is the leading cause of kidney failure worldwide, but for almost two decades there have been no new treatments to protect kidney function," noted study lead author Vlado Perkovic. He's a professor at The George Institute for Global Health at Oxford University in the United Kingdom.

"This definitive trial result is a major medical breakthrough as people with diabetes and kidney disease are at extremely high risk of kidney failure, heart attack, stroke and death," Perkovic said in a university news release. "We now have a very effective way to reduce this risk using a once-daily pill."

The research was paid for by drug company Janssen, which makes Invokana. The study involved more than 4,400 patients with diabetes and kidney disease across 34 countries. Half took Invokana and half took a "dummy" placebo pill. All of them received care for kidney disease according to current guidelines.

Those who took Invokana had a 30% lower risk of developing kidney failure, a 30% lower risk of dying from kidney failure or heart disease, a 20% lower risk of major heart events such as heart attack, stroke, or heart-related death, and a 39% lower risk of hospitalization for heart failure, the researchers reported.

The findings were published April 15 in the New England Journal of Medicine.

There was no higher risk of major side effects among those who took Invokana, according to the study, which was also due to be presented Monday at the ISN World Congress of Nephrology, in Melbourne, Australia.

Invokana is from a class of diabetes medicines known as sodium glucose transporter 2 (SGLT2) inhibitors.

Study co-author Meg Jardine, associate professor at The George Institute, said, "With 5 million people worldwide predicted to have kidney failure by 2035, this is a major breakthrough."

Two experts in diabetes and renal (kidney) care who read over the new study agreed the findings are significant.

"Upwards of 40% of end-stage renal disease patients have diabetes as the cause of their renal failure," noted Dr. Maria DeVita, chief of nephrology at Lenox Hill Hospital in New York City.

She explained that SGLT2 inhibitor medicines like Invokana work by blocking the "reuptake" of glucose within the kidney. More of this blood sugar, as well as salt, are therefore excreted harmlessly in urine instead of lingering in the kidneys where they can do damage, DeVita said.

So, Invokana "may substantially change the trajectory of kidney decline, preserving kidney function for years longer than we thought possible for the long term," DeVita said. "This is wonderful news for those with diabetic kidney disease."

Dr. Guy Mintz directs cardiovascular health at the Sandra Atlas Bass Heart Hospital in Manhasset, N.Y. He also believes the new findings are "exciting."

"With another impressive study of this family of medications, SGLT2 inhibitors should now be utilized in all type 2 diabetic patients with kidney disease and increased cardiovascular risk," as long as there are no reasons not to do so, Mintz believes.

"This is another tool in our belt to reduce progressive kidney disease and cardiac events in our type 2 diabetic population with kidney disease," he said.    

https://www.drugbank.ca/drugs/DB08907

https://en.wikipedia.org/wiki/Canagliflozin

 



Common Diabetes Drug Invokana (canagliflozin) May Also Shield Kidneys, Heart 

Balversa (erdafitinib) Approved for Advanced Bladder Cancer

Balversa (erdafitinib) has been approved by the U.S. Food and Drug Administration to treat adults with advanced or spreading bladder cancer caused by a genetic defect called FGFR3 or FGFR2, the agency said in a news release.

"We're in an era of more personalized or precision medicine, and the ability to target cancer treatment to a patient's specific genetic mutation or biomarker is becoming the standard, with advances being made in new disease types. Today's approval represents the first personalized treatment targeting susceptible FGFR genetic alternations for patients with metastatic bladder cancer," said Dr. Richard Pazdur, director of the FDA's Oncology Center of Excellence.

Bladder cancer is the sixth most common cancer in the United States, the FDA said. About 20 percent of people with the disease have an FGFR mutation.

Balversa was clinically studied in a trial involving 87 people with advanced or metastatic bladder cancer and the FGFR3 or FGFR2 genetic mutation who hadn't responded to chemotherapy, the FDA said. About one-third of those given the drug had a complete or partial response to the medication; the average response lasting about 5 1/2 months.

Common side effects of Balversa included a jump in phosphate levels, mouth sores, feeling tired, changes in kidney function, diarrhea, dry mouth and changes in liver function.

Balversa may trigger serious eye problems, including inflamed eyes, inflamed cornea and disorders of the retina, the agency warned.

Doctors and other health professionals should tell men with female partners of child-bearing potential to use contraception during treatment with Balversa and for one month after the last dose, the FDA said. Women who are pregnant or breastfeeding shouldn't take Balversa because it may harm a developing fetus or newborn.

https://en.wikipedia.org/wiki/Erdafitinib

https://pubchem.ncbi.nlm.nih.gov/compound/Erdafitinib

Balversa (erdafitinib) Approved for Advanced Bladder Cancer 

Mayzent Approved for Relapsing MS

Mayzent (siponimod) pills have been approved by the U.S. Food and Drug Administration for adults with relapsing multiple sclerosis (MS).

"Multiple sclerosis can have a profound impact on a person's life," said Dr. Billy Dunn, director of the agency's Division of Neurology Products.

MS is an autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. Most people have initial symptoms between the ages of 20 and 40, and MS strikes more women than men, the FDA said in a news release.

Many people with MS are left permanently disabled and worsen over time, the agency said.

Mayzent's effectiveness was shown in clinical studies of 1,651 people. Progression of disability was significantly lower among those who took Mayzent than in a group that took a placebo. Mayzent also decreased the number of relapses, the FDA said.

The drug must be accompanied by a patient medication guide that describes the medication's uses and risks. Since Mayzent may raise the risk of infections, users should have a complete blood count before treatment starts. And users should contact their doctor if they have any vision changes, changes in heart rate or trouble breathing, the FDA said.

Since Mayzent may harm a developing fetus, women of childbearing age should use contraception during treatment and for 10 days after stopping the drug.

Mayzent's most common side effects include headache, high blood pressure and liver problems.

https://en.wikipedia.org/wiki/Siponimod

Mayzent Approved for Relapsing MS 

FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose

In continuation of my update on naloxone 

   

The first generic naloxone nasal spray to treat opioid overdose has received approval from the U.S. Food and Drug Administration.

Teva Pharmaceuticals' lifesaving product is also the first generic naloxone nasal spray approved for use by people without medical training. There was already a brand-name spray (Narcan) for emergency use by untrained people, such as family members and bystanders.

The need is urgent. On average, more than 130 Americans die every day from overdoses of opioids -- including prescription painkillers such as fentanyl, oxycodone (OxyContin), hydrocodone (Vicodin) and morphine, as well as illegal drugs such as heroin or drugs sold as heroin, the FDA said.

"In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible," said Dr. Douglas Throckmorton, deputy center director for regulatory programs in the FDA's Center for Drug Evaluation and Research.

"In addition to this approval of the first generic naloxone nasal spray, moving forward we will prioritize our review of generic drug applications for naloxone," he added.

When someone overdoses on opioids, breathing may become shallow or stop completely, leading to death if no one intervenes. If administered quickly, naloxone can counter the effects within minutes.

Throckmorton said in an agency news release that the FDA is also helping drugmakers pursue approval of an over-the-counter naloxone product, and "exploring other ways to increase availability of naloxone products intended for use in the community."

The FDA is also considering whether naloxone should be routinely prescribed along with all or some opioid prescriptions in order to reduce the risk of overdose.

"Altogether, these efforts have the potential to put a vital tool for combating opioid overdose in the hands of those who need it most -- friends and families of opioid users, as well as first responders and community-based organizations," Throckmorton said.

Nearly 400,000 people in the United States died of opioid overdoses between 1999 and 2017, according to the U.S. Centers for Disease Control and Prevention.

"We're committed to working with other federal, state and local officials, as well as health care providers, patients and communities across the country to combat the staggering human and economic toll created by opioid abuse and addiction," Throckmorton said in the news release.

 Ref : https://en.wikipedia.org/wiki/Naloxone

FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose  

Asparagus: A Tasty Spring Veggie That Boosts Gut Health

Asparagus is a great spring vegetable that can be a tasty side dish or the starring ingredient in the main course like risotto. And it's more than just delicious asparagus is great for digestive health, too.

It's a prebiotic food, meaning it feeds the helpful bacteria that live in your gut. These good bacteria are responsible for everything from signalling your immune system and keeping digestion in check to producing vital B vitamins.

When shopping for asparagus, look for spears that are free of blemishes and dry spots, and tips that are closed and firm. Use asparagus promptly it can spoil quickly.

Miso asparagus is an easy side dish that can also be enjoyed as a main dish when served over salad or with sliced chicken. Miso is a paste made from fermented soybeans. It's a probiotic food, which has similar health benefits. Though it has a high salt content, it's typically used in small amounts. 

Asparagus: A Tasty Spring Veggie That Boosts Gut Health 

Ginger: A Flavorful and Healing Root

 Zesty ginger is more than just a great way to dress up your favorite recipes. It contains a potent immunity booster -- its active compound gingerol is an antibacterial and anti-inflammatory compound.

Ginger is also a source of vitamin C and the minerals potassium and magnesium.

Ginger root is inexpensive and easy to find in the produce aisle of your local grocery store. Look for a piece that's firm and smooth. It may have many nubs, but they shouldn't be shrivelled. The skin should be a light brown and fairly smooth. Ginger keeps well for up to a few weeks in the produce bin of your fridge. Keep it wrapped in a paper towel and change the towel whenever it gets damp.

Many people peel ginger with a spoon, scraping off the skin with an edge. But a veggie peeler works too and may be faster. When a recipe calls for minced ginger, after peeling, make horizontal slices and then cut each slice into matchsticks and cut the match sticks into tiny pieces. For grated ginger, you could use a mini food processor or, even better, a microplane -- just run one trimmed end of a piece of ginger across the metal mesh and let the ginger and its juice fall into a bowl.

Ginger is perfect for jazzing up salad dressings and marinades and for making a herbal tea. 

Ginger: A Flavorful and Healing Root  

Could Diabetes Drug Metformin Help Keep People Slim?

New research suggests a first-line drug for treating type 2 diabetes   'metformin'  may help people with pre-diabetes maintain long-term weight loss.

People who lost weight while taking metformin maintained a loss of about 6% of their body weight for six to 15 years. People who lost weight through lifestyle changes -- eating healthily and exercising regularly -- managed to keep off just under 4% of their initial body weight for the same period, the study found.

Metformin doesn't seem to be particularly helpful for shedding pounds in the first place, though. In fact, an earlier phase of the study found that people were much more likely to lose 5% or more of their body weight through lifestyle changes -- healthy eating and exercising -- than by using metformin.

"Although lifestyle changes were superior for inducing weight loss early on, metformin was better for long-term weight maintenance," said senior study author Dr. Kishore Gadde. He's a professor in heart disease prevention at the Pennington Biomedical Research Center in Baton Rouge, La.

Not everyone is convinced that metformin can keep you slim, however. After reviewing the findings, Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center in New York City, said, "This study was very well done, but it doesn't show metformin is effective for everyone. The ones on metformin who did lose weight only regained a little less weight."

He added that metformin isn't well-tolerated by a lot of people. It can cause digestive problems, such as nausea and diarrhoea.

An  effective intervention for losing weight and maintaining that loss is clearly needed. Nearly three-quarters of the American population is overweight or obese -- a major risk factor for type 2 diabetes, according to the U.S. Centers for Disease Control and Prevention.

Losing a significant amount of weight more than 5% of your body weight  seems to help prevent pre-diabetes from turning into type 2 diabetes, and can help delay the progression of type 2 diabetes.

The latest study was a continuation of the three-year diabetes prevention clinical trial that compared three different groups of people with pre-diabetes to see what type of intervention would help prevent type 2 diabetes from developing. One group was given metformin, another was coached on intensive lifestyle changes, and the third group was given a placebo.

This study found that lifestyle changes led to the greatest initial weight loss, followed by the metformin group, according to Gadde.

From the original study group -- more than 3,000 people -- just over 1,000 lost more than 5% of their body weight.

The researchers followed this group for as long as 15 years to see who maintained their weight loss.

People taking metformin had the greatest weight loss from years six to 15, according to the study. The study also found that being older and losing a greater amount of weight in the first year were consistent predictors of lasting weight loss, the study authors said.

Gadde said it's not exactly clear why the metformin group was better at maintaining weight loss. "Metformin does reduce food intake a little bit, but it's not a dramatic effect. And, from what we know, it doesn't significantly alter energy expenditure."

He said other recent research suggests that metformin may alter the body's microbiome (the healthy bacteria in your gut). It also seems that metformin may have some effects on muscle function. But Gadde said, more research is necessary to know for sure.

Could Diabetes Drug Metformin Help Keep People Slim?

Long-Term Antibiotic Use May Up Women's Odds for Heart Trouble

Antibiotics can be lifesaving, but using them over a long period might raise the odds of heart disease and stroke in older women, a new study suggests.

Researchers tracked the health of nearly 36,500 U.S. women over an average follow-up of nearly eight years. During that time, more than a thousand developed heart disease.

The study found that women aged 60 and older who used antibiotics for two months or longer were 32% percent more likely to develop heart disease than those who did not use antibiotics.

Women aged 40 to 59 who took antibiotics for longer than two months had a 28% higher risk than those who did not take the drugs, said a team led by Lu Qi. He directs the Tulane University Obesity Research Center in New Orleans.

Said another way, the results mean that for older women who take antibiotics for two months or more, 6 per 1,000 would go on to develop heart disease, compared with 3 in 1,000 among those who did not take the drugs.

There was no increased risk of heart disease among women aged 20 to 39 who took antibiotics, according to the study published April 24 in the European Heart Journal.

"This is an observational study and so it cannot show that antibiotics cause heart disease and stroke, only that there is a link between them," Qi said in a journal news release. "It's possible that women who reported more antibiotic use might be sicker in other ways that we were unable to measure, or there may be other factors that could affect the results that we have not been able take account of."

However, the researchers did take into account other factors, including age, race, sex, diet and lifestyle, reasons for antibiotic use, overweight or obesity, other diseases and medication use.

The most common reasons for antibiotic use among women in the study were respiratory infections, urinary tract infections and dental problems.

So what could be the link between antibiotics and heart risk?

One possible reason could lie in the fact that antibiotics do alter the balance of gut microbes, destroying good bacteria and increasing the proportion of viruses, bacteria or other microbes that can cause disease, Qi suggested.

"Antibiotic use is the most critical factor in altering the balance of microorganisms in the gut," he said, and "previous studies have shown a link between alterations in the microbiotic environment of the gut and inflammation and narrowing of the blood vessels, stroke and heart disease."

Study first author Yoriko Heianza is a research fellow at Tulane University. She noted that, as the women in the study aged, "they were more likely to need more antibiotics, and sometimes for longer periods of time, which suggests a cumulative effect may be the reason for the stronger link in older age between antibiotic use and cardiovascular disease."

According to Qi, the take-home message from the new study is that "antibiotics should be used only when they are absolutely needed. Considering the potentially cumulative adverse effects, the shorter time of antibiotic use, the better."

Dr. Eugenia Gianos directs Women's Heart Health at Lenox Hill Hospital in New York City. She wasn't involved in the new research, but said the findings are "interesting and warrant further analysis."

Gianos agreed that the study couldn't prove cause and effect. "It is very possible that patients who require antibiotics for an infection have a worse underlying infectious or inflammatory process, and that the systemic effects of these diseases are what cause cardiovascular disease," she reasoned.

But the interplay between antibiotics, the gut's "microbiome" and the cardiovascular system could be important as well, Gianos said.

Long-Term Antibiotic Use May Up Women's Odds for Heart Trouble 

FDA Approves Kalydeco (ivacaftor) as First and Only CFTR Modulator to Treat Eligible Infants with CF as Early as Six Months of Age

In continuation of my update on Kalydeco (ivacaftor) 

Vertex Pharmaceuticals Incorporated  announced the U.S. Food and Drug Administration (FDA) approved Kalydeco (ivacaftor) for use in children with cystic fibrosis (CF) ages six months to less than 12 months who have at least one mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Kalydeco based on clinical and/or in vitro assay data. Kalydeco is already approved in the U.S., Canada and EU for the treatment of CF in patients ages 12 months and older.

“Today’s approval for Kalydeco allows physicians to begin treating the underlying cause of CF in eligible infants as young as six months of age for the first time, with the potential to modify the course of the disease,” said Margaret Rosenfeld, M.D., MPH, Seattle Children’s Research Institute and Department of Pediatrics, University of Washington School of Medicine.

This FDA approval is based on data from a 24-week Phase 3 open-label safety cohort (ARRIVAL) of 11 children with CF aged six months to less than 12 months who have one of 10 mutations in the CFTR gene (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H). The study demonstrated a safety profile similar to that observed in previous Phase 3 studies of older children and adults; most adverse events were mild or moderate in severity, and no patient discontinued therapy due to adverse events. The most common adverse events (≥30%) were cough (64%), nasal congestion (36%) and rhinorrhea (36%). Three serious adverse events, all considered unrelated to study treatment by the investigators, were observed in three patients.

Mean baseline sweat chloride for the children in this cohort was 101.5 mmol/L (n=11). Following 24 weeks of treatment with Kalydeco, the mean sweat chloride level was 43.1 mmol/L (n=6). In the six subjects with paired sweat chloride samples at baseline and week 24, there was a mean absolute change of -58.6 mmol/L (95% CI; -75.9, -41.3).

Results of this study were presented at the 32nd Annual North American Cystic Fibrosis Conference in October 2018.

“The manifestations of CF are often present at birth, which underscores our relentless commitment to reach the youngest CF patients possible in our clinical trials,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex. “As an important outcome of these efforts, we are now able to treat infants with cystic fibrosis as early as six months of age with Kalydeco.”

Kalydeco was first approved in 2012 in the U.S. and is now available in more than 40 countries with more than 5,000 patients on therapy. For more information on Kalydeco, prescribing information, or patient assistance programs, visit Kalydeco.com or VertexGPS.com.

https://en.wikipedia.org/wiki/Ivacaftor

FDA Approves Kalydeco (ivacaftor) as First and Only CFTR Modulator to Treat Eligible Infants with CF as Early as Six Months of Age