FDA Expands Approval of Gilenya (fingolimod) to Treat Multiple Sclerosis in Pediatric Patients

In continuation of my update on fingolimod

The U.S. Food and Drug Administration today approved Gilenya (fingolimod) to treat relapsing multiple sclerosis (MS) in children and adolescents age 10 years and older. This is the first FDA approval of a drug to treat MS in pediatric patients.

“For the first time, we have an FDA-approved treatment specifically for children and adolescents with multiple sclerosis,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Multiple sclerosis can have a profound impact on a child’s life. This approval represents an important and needed advance in the care of pediatric patients with multiple sclerosis.”

Gilenya was first approved by the FDA in 2010 to treat adults with relapsing MS.

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function and appearance of new symptoms, called relapses or flare-ups, are initially followed by recovery periods (remissions). Over time, recovery may be incomplete, leading to progressive decline in function and increased disability. Most people with MS experience their first symptoms, like vision problems or muscle weakness, between the ages of 20 to 40. Two to five percent of people with MS have symptom onset before age 18 and estimates suggest that 8,000 to 10,000 children and adolescents in the U.S. have MS.

The clinical trial evaluating the effectiveness of Gilenya in treating pediatric patients with MS included 214 evaluated patients aged 10 to 17 and compared Gilenya to another MS drug, interferon beta-1a. In the study, 86 percent of patients receiving Gilenya remained relapse-free after 24 months of treatment, compared to 46 percent of those receiving interferon beta-1a.

The side effects of Gilenya in pediatric trial participants were similar to those seen in adults. The most common side effects were headache, liver enzyme elevation, diarrhea, cough, flu, sinusitis, back pain, abdominal pain and pain in extremities.

Gilenya must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Serious risks include slowing of the heart rate, especially after the first dose. Gilenya may increase the risk of serious infections. Patients should be monitored for infection during treatment and for two months after discontinuation of treatment. A rare brain infection that usually leads to death or severe disability, called progressive multifocal leukoencephalopathy (PML) has been reported in patients being treated with Gilenya. PML cases usually occur in patients with weakened immune systems. Gilenya can cause vision problems. Gilenya may increase the risk for swelling and narrowing of the blood vessels in the brain (posterior reversible encephalopathy syndrome). Other serious risks include respiratory problems, liver injury, increased blood pressure and skin cancer. Gilenya can cause harm to a developing fetus; women of child-bearing age should be advised of the potential risk to the fetus and to use effective contraception.

Neonicotinoids may alter estrogen production in humans | INRS

Neonicotinoids-a class of neuro-active insecticides chemically similar to nicotine (family includes acetamiprid, clothianidin, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam) are currently the most widely used pesticides in the world and frequently make headlines because of their harmful effects on honeybees and other insect pollinators. Now, a study published in the prestigious journal Environmental Health Perspectives, indicates they may also have an impact on human health by disrupting our hormonal systems. This study by INRS professor Thomas Sanderson indicates that more work must be done on the potential endocrine-disrupting effects of neonicotinoids. 

The Quebec government has recently decided to more strictly regulate the use of certain pesticides, including neonicotinoids, which are widely used by Quebec farmers to control crop pests. Neonicotinoids act on insects’ nervous systems, killing them by paralysis. Very little research has been done on their effects on human health, but INRS Professor Sanderson and Ph.D. student Élyse Caron-Beaudoin have taken on the challenge. 

Both researchers have long been interested in the mechanisms of endocrine disrupting chemicals and they wanted to determine whether neonicotinoids belong to this class of compounds. “Endocrine disrupters are natural or synthetic molecules that can alter hormone function,” says Caron-Beaudoin, the study’s main author. ”They affect the synthesis, action, or elimination of natural hormones, which can lead to a wide variety of health effects.”  

The research duo has developed methods to test the effect of neonicotinoids on the production of estrogens, essential hormones with several biological functions. By targeting aromatase, a key enzyme in the synthesis of estrogens, they were able to test the impact of three neonicotinoids on breast cancer cells in culture after exposure to concentrations similar to those found in the environment in agricultural areas. 

The results of the study show an increase in aromatase expression and a unique change in the pattern in which aromatase was expressed, which is similar to that observed in the development of certain breast cancers. “However, as these results were obtained in a cellular model of breast cancer, we cannot necessarily conclude that exposure to pesticides at concentrations similar to those in the human environment would cause or promote cancer,” cautions Professor Sanderson. This study is the first evidence that neonicotinoids have an effect on aromatase gene expression and may potentially alter estrogen production. Hormonal disturbance by these pesticides will need to be confirmed in future studies, but the results obtained by the INRS team indicate that it caution should be exercised in the management and use of neonicotinoid insecticides.

Ref : https://ehp.niehs.nih.gov/EHP2698/

Neonicotinoids may alter estrogen production in humans | INRS

FDA Approves Jynarque (tolvaptan) to Slow Kidney Function Decline in Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease

Otsuka Pharmaceutical Co., Ltd. (Otsuka) announces that the U.S. Food and Drug Administration (FDA) has approved Jynarque (tolvaptan) as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

ADPKD is a genetic disease with consequences that can lead to dialysis or kidney transplantation. It is a progressively debilitating and often painful disorder in which fluid-filled cysts develop in the kidneys over time. These cysts enlarge the kidneys and impair their ability to function normally, leading to kidney failure in most patients.3 ADPKD is diagnosed in approximately 140,000 people in the U.S.,4,5 and impacts families across multiple generations, since a parent with ADPKD has a 50 percent chance of passing the disease on to each of their children. 

The efficacy of tolvaptan was demonstrated in two pivotal trials, lasting one year and three years, respectively. In the one-year REPRISE study, the primary endpoint was the treatment difference in the change of eGFR from pretreatment baseline to post-treatment follow-up, annualized by dividing by each subject’s treatment duration. In the randomized period, the change of eGFR from pretreatment baseline to post-treatment follow-up was −2.3 mL/min/1.73 m2/year with tolvaptan as compared with −3.6 mL/min/1.73 m2/year with placebo, corresponding to a treatment effect of 1.3 mL/min/1.73 m2/year (p <0.0001). In the three-year TEMPO 3:4 study, tolvaptan reduced the rate of decline in eGFR by 1.0 mL /min /1.73m2 /year (95 % confidence interval of 0.6 to 1.4) as compared to placebo in patients with earlier stages of ADPKD. In the extension trial, eGFR differences produced by the third year of the TEMPO 3:4 trial were maintained over the next 2 years of Jynarque treatment.

The primary endpoint in TEMPO 3:4 study was the intergroup difference for rate of change of total kidney volume (TKV) normalized as a percentage. The trial met its pre-specified primary endpoint of 3-year change in TKV (p<0.0001). The difference in TKV between treatment groups mostly developed within the first year, the earliest assessment, with little further difference in years two and three. In years 4 and 5 during the TEMPO 3:4 extension trial, both groups received Jynarque and the difference between the groups in TKV was not maintained. Tolvaptan has little effect on kidney size beyond what accrues during the first year of treatment. The key secondary composite endpoint (ADPKD progression) was time to multiple clinical progression events of: 1) worsening kidney function (defined as a persistent 25% reduction in reciprocal serum creatinine during treatment (from end of titration to last on-drug visit); 2) medically significant kidney pain (defined as requiring prescribed leave, last-resort analgesics, narcotic and anti-nociceptive, radiologic or surgical interventions); 3) worsening hypertension (defined as a persistent increase in blood pressure category or an increased anti-hypertensive prescription); 4) worsening albuminuria (defined as a persistent increase in albumin/creatinine ratio category). The relative rate of ADPKD-related events was decreased by 13.5% in tolvaptan-treated patients, (44 vs. 50 events per 100 person-years; hazard ratio, 0.87; 95% CI, 0.78 to 0.97; p=0.0095). As shown in the table below, the result of the key secondary composite endpoint was driven by effects on worsening kidney function and kidney pain events. In contrast, there was no effect of tolvaptan on either progression of hypertension or albuminuria. Few subjects in either arm required a radiologic or surgical intervention for kidney pain. Most kidney pain events reflected use of a medication to treat pain such as use of paracetamol, tricyclic antidepressants, narcotics and other non-narcotic agents.

Jynarque can cause serious and potentially fatal liver injury, and acute liver failure requiring liver transplantation has been reported. Jynarque has been associated with elevations of blood alanine and aspartate aminotransferases (ALT and AST), with infrequent cases of concomitant elevations in bilirubin-total (BT). To ensure the safety of patients taking Jynarque, it is necessary to measure ALT, AST and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for 18 months and every 3 months thereafter, for as long as the patient is on Jynarque (tolvaptan) treatment. Because of the risks of serious liver injury, Jynarque is available only through a restricted distribution program supported by a Risk Evaluation and Mitigation Strategy (REMS) Program approved by the FDA. For more information about Jynarque, please visit www.JYNARQUE.com.

"The progressive nature of ADPKD means that kidney function gets worse over time, eventually leading to end-stage renal disease. This progression happens more rapidly for some patients than others.” said Michal Mrug, M.D., Associate Professor at the University of Alabama at Birmingham and investigator on the REPRISE trial. “Today’s approval is great news for adults at risk of rapidly progressing ADPKD because by slowing the decline in kidney function, this therapy may give them more time before kidney transplant or dialysis.”

Andy Betts, CEO of the PKD Foundation, observed, “Today is an historic day in providing hope to patients with autosomal dominant polycystic kidney disease, and we are thrilled to be a part of this first milestone in treatment. For the past 35 years, our goal has been to walk with PKD patients every step of the way. It is gratifying to play a part in the inception of the discovery of this treatment, and to see it come to fruition. We hope that this is just the beginning of a new chapter for adults at risk of rapidly progressing ADPKD who suffer from the disease.”

Also, Tatsuo Higuchi, president and representative director of Otsuka Pharmaceutical Co., Ltd., commented, “This approval is important news for many adults at risk of rapidly progressing ADPKD in the U.S., who have had no therapeutic alternatives to delay the eventual end-stage interventions of dialysis or kidney transplantation. We are humbled to be able to offer an earlier, proactive course of action to slow the progression of this disease, which we know means so much to patients, their families and healthcare providers. Simultaneously, we are grateful to the patients and researchers who through their continued commitment made this milestone possible.”

FDA Approves Jynarque (tolvaptan) to Slow Kidney Function Decline in Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease

What Does the Research Say About Coffee and Your Health?

In continuation of my update on coffee...

Coffee-Cup of joe. Java. No matter what you call it, millions of people worldwide wake up and fuel their day with it. And though consumers might be jittery about the recent court battle in California over cancer warnings, experts say most of the science actually indicates coffee could have health benefits.

"The overall picture is quite clear," said Dr. Frank Hu, chair of nutrition at Harvard University's T.H. Chan School of Public Health. "There is no long-term increased risk of major chronic disease, including diabetes, cardiovascular disease or even cancer."

The java confusion stems over an eight-year court case. A Los Angeles-based judge's preliminary decision last month requires cancer warning labels because of concerns about acrylamide, a chemical produced during the roasting process. Acrylamide also is present in some fried or roasted starchy foods, including french fries, potato chips, breakfast cereals and toast. It's also found in cigarette smoke. The judge gave the coffee industry a few weeks to file appeals and could issue a final ruling late this month.

But there's little evidence acrylamide levels in food cause cancer in humans. Studies have found no consistent evidence acrylamide exposure in food is associated with cancer risk, according to the U.S. National Cancer Institute. The World Health Organization's International Agency for Research on Cancer reviewed more than 1,000 human and animal studies and issued a statement in 2016 that "found no conclusive evidence for a carcinogenic effect of drinking coffee."

"The California judge's decision to label coffee as a cancer risk is really inconsistent with the scientific literature," Hu said. "It's very misleading and has already caused a huge amount of confusion in the general public. The health outcomes have been remarkably consistent."

Hu was senior author of a 2015 study in the journal Circulation that concluded people who regularly drink moderate amounts of coffee daily -- fewer than five cups -- experienced a lower risk of death from heart and neurological diseases.

About four years ago, the U.S. government gave coffee its OK, too. The Department of Agriculture's dietary guidelines for all Americans, published every five years as a go-to source for nutrition advice, said three to five cups a day, which can be up to 400 milligrams a day of caffeine, can be part of a healthy diet. The American Heart Association suggests that people who have an arrhythmia, an abnormal heart rhythm, talk to their health care provider about caffeine intake.

"This guidance on coffee is informed by strong and consistent evidence showing that, in healthy adults, moderate coffee consumption is not associated with an increased risk of major chronic diseases (e.g., cancer) or premature death, especially from cardiovascular disease," the federal guidelines say. "However, individuals who do not consume caffeinated coffee or other caffeinated beverages are not encouraged to incorporate them into their eating pattern."

More recently, a review of more than 200 studies published last fall in the BMJ concluded three to four cups a day may be "more likely to benefit health than harm." It found a lower risk of liver disease and some cancers in coffee drinkers, and a lower risk of dying from stroke.

All of that should be good news to the people around the world who drink more than 1.1 billion cups of coffee each day.

But it's still easy to be confused. A quick search for coffee and health online yields hundreds, even thousands, of results.

Studies abound -- some funded by the coffee industry. For example, a European Journal of Nutritionstudy investigated the effects of coffee and its antioxidant properties and found no effect. Researchers took blood samples of 160 volunteers who drank up to three to five cups of coffee or water each day for eight weeks.

"Up to five cups of coffee per day had no detectable effect, either beneficial or harmful, on human health," that study concluded. It was funded by Kraft Foods, which makes Maxwell House coffees.

Of course, "no one is talking about coffee as a magic bullet," Hu said. He and other experts say it's important to keep track of the bigger picture, with the focus on moderation and dietary patterns.

"You can't pin anything on any one specific lifestyle behavior, particularly with diet," said Alice Lichtenstein, a senior scientist and director of the Cardiovascular Nutrition Laboratory at Tufts University in Boston.

"When we talk about diet, it should really be about the whole package, not single items. Right now, the majority of the evidence suggests there may be a health benefit from drinking coffee and there doesn't seem to be any disadvantage. Of course, with a caveat that you don't want to add a lot of cream and sugar, or to use it as an excuse to have a few cookies or a pastry. Then, there is a downside," said Lichtenstein, a professor of nutrition science and policy who also was an advisor on the federal dietary guidelines.

"We have a tendency to focus on one or two specific foods or beverages, and that's when the whole floor falls out from under us."

FDA Approves Tavalisse (fostamatinib disodium hexahydrate) for Chronic Immune Thrombocytopenia

Rigel Pharmaceuticals, Inc.   announced that the U.S. Food and Drug Administration (FDA) approved Tavalisse (fostamatinib disodium hexahydrate) for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Tavalisse is an oral spleen tyrosine kinase (SYK) inhibitor that targets the underlying autoimmune cause of the disease by impeding platelet destruction, providing an important new treatment option for adult patients with chronic ITP. Rigel plans to launch Tavalisse in the United States in late May 2018.

"Chronic ITP is challenging to treat because the heterogeneity of the disease makes it difficult to predict how an individual patient will respond to available treatments and not all patients can find a treatment that works well for them," said James Bussel, M.D., professor emeritus of pediatrics at Weill Cornell Medicine and the principal study investigator on the FIT Phase 3 program. Dr. Bussel has served as a consultant and paid member of the advisory board for Rigel Pharmaceuticals, Inc. "The FDA approval of fostamatinib arms physicians with a new treatment option, which works via a novel mechanism."

The FDA approval of Tavalisse was supported by data from the FIT clinical program, which included two randomized placebo-controlled Phase 3 trials (Studies 047 and 048) and an open-label extension (Study 049), as well as an initial proof of concept study. The New Drug Application (NDA) included data from 163 ITP patients and was supported by a safety database of more than 4,600 subjects across other indications in which fostamatinib has been evaluated.

"People living with chronic ITP often feel they have an invisible disease -- one that can not only impact quality of life, but also be life threatening," said Caroline Kruse, executive director of the Platelet Disorder Support Association, a patient advocacy organization dedicated to ITP patients. "That's why we encourage members of our community to learn about their disease, understand treatment strategies, and seek support so that they can advocate for their best care. The availability of a new treatment option provides the ITP community with more choices."

FDA Approves Tavalisse (fostamatinib disodium hexahydrate) for Chronic Immune Thrombocytopenia

Scientists successfully test anti-alcoholism drug in animal models

Scientists at The University of Texas at Austin have successfully tested in animals a drug that, they say, may one day help block the withdrawal symptoms and cravings that incessantly coax people with alcoholism to drink. If eventually brought to market, it could help the more than 15 million Americans, and many more around the world who suffer from alcoholism stay sober.

If what has been shown to work in worms and rats addicted to alcohol can eventually be demonstrated to work in humans with minimal side effects, it would be a true breakthrough. Scientists point out, however, that the drug has more hoops to go through before that happens.

There are already drugs on the market prescribed to help people break their addiction to alcohol, but for many patients, they are not very effective and have negative side effects. The new drug, called JVW-1034, targets a different molecular pathway in the body and so far, in animal models, has no obvious side effects.

"There's clearly a huge need for something different and better," said James Sahn, research scientist in chemistry at UT Austin and co-first author of a new paper. "That's where our approach shines. It's modulating a pathway that doesn't seem to be associated with any of the other drugs that are available."

The researchers reported their findings in the journal Neuropsychopharmacology and have filed a patent on the drug.

The paper's other co-first authors are Luisa Scott, a research associate in neuroscience at UT Austin; and Antonio Ferragud, a postdoctoral associate at Boston University School of Medicine (BUSM). Senior authors are Stephen Martin, professor of chemistry, and Jonathan Pierce, associate professor of neuroscience, both at UT Austin; and Valentina Sabino, associate professor of pharmacology and psychiatry at BUSM.

While the drug is promising, the researchers plan to optimize its chemical properties to have a better chance of being effective in humans. They envision a pill that could one day be taken to block alcohol withdrawal symptoms and cravings, helping people avoid relapsing. But it isn't clear whether such a drug could actually cure alcoholism. That's because there are genetic and regulatory underpinnings to the disorder that researchers don't fully understand yet and that may not be permanently altered by this drug. But even a drug that could be taken chronically or in times of stress could have a huge benefit for people suffering from alcoholism.

"If we could achieve a medication that is effective for more people and doesn't have the negative side effects that some of these drugs have, that would be game-changing," said Martin.

It might also make a dent in the $250 billion annual cost of alcohol misuse in the U.S., as estimated by a 2015 study.

This work was supported by The Robert A. Welch Foundation, the Dell Medical School's Texas Health Catalyst program, donations from individuals including Tom Calhoon and June Waggoner through a crowdfunding program called Hornraiser, and the National Institute on Alcohol Abuse and Alcoholism.

Screening in Worm and Rat Models

The drug JVW-1034 was named in honor of James Virgil Waggoner, a UT Austin alumnus, businessman and philanthropist who donated funds to establish the university's Waggoner Center for Alcohol and Addiction Research.

It was one of many potential compounds developed in the lab by chemists Stephen Martin and James Sahn, which they suspected would interact with a cell receptor found throughout the central nervous systems of animals, called sigma 2. Other researchers had shown that that receptor was involved in cocaine addiction. So Martin and Sahn wondered whether it might also be involved in alcoholism.

To screen their compounds, their colleague Luisa Scott created hungover worms. She exposed C. elegans worms to alcohol for a day and then took it away. She could tell they were hungover because when she placed a tasty-smelling substance on the other side of their petri dish, they sluggishly meandered over.

"It smells like movie theater popcorn," Scott said. "Normal worms are quite speedy, but withdrawal worms go very slowly."

When she administered JVW-1034 to the hungover worms, they once again raced across the dish just like worms that had never been exposed to alcohol.

In follow-up experiments, Scott demonstrated that the receptor sigma 2 was in fact the target of JVW-1034. This also demonstrated for the first time that sigma 2 is involved in alcohol addiction. She noted that it can be difficult to identify which parts of an animal's cells a drug interacts with. In fact, scientists still don't know the targets of many drugs that have been in use for many years.

"So for me, being able to show that this really is the target it binds to, that's a big deal," she said.

Finally, a group of collaborators led by Valentina Sabino tested JVW-1034 in alcoholic rats. Alcoholic rats that could freely access alcohol and were then given JVW-1034 dramatically reduced their alcohol consumption.

The researchers are developing several other promising drugs that target the sigma 2 receptor to treat other neurological disorders, including traumatic brain injury, neuropathic pain and Alzheimer's disease.

FDA Approves Tagrisso (osimertinib) as First-Line Treatment for EGFR-Mutated Non-Small Cell Lung Cancer

In continuation of my update on Osimertinib, AstraZeneca,announced that the US Food and Drug Administration (FDA) has approved Tagrisso (osimertinib) for the 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or exon 21 L858R mutations), as detected by an FDA-approved test. The approval is based on results from the Phase III FLAURA trial, which were presented at the European Society of Medical Oncology 2017 Congress and published in the New England Journal of Medicine.

Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit at AstraZeneca, said: “Today’s FDA approval of Tagrisso in the 1st-line setting is an exciting milestone for patients and our company. Tagrisso delivered unprecedented median progression-free survival data across all pre-specified patient subgroups, including patients with or without CNS metastases, and could prolong the lives of more patients without their tumors growing or spreading.”

Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA trial, from Winship Cancer Institute of Emory University, Atlanta, said: “The approval of osimertinib (Tagrisso) in the 1st-line setting represents a major advance in the treatment of patients with EGFR mutations and a significant change in the treatment paradigm. Osimertinib (Tagrisso) provides robust improvements in progression-free survival with no unexpected safety signals compared to the previous generation of EGFR inhibitors.”

The FLAURA trial compared Tagrisso to current 1st-line EGFR tyrosine kinase inhibitors (TKIs), erlotinib or gefitinib, in previously untreated patients with locally advanced or metastatic EGFR-mutated (EGFRm) NSCLC. Tagrisso met the primary endpoint of progression-free survival (PFS) (see table below). PFS results with Tagrisso were consistent across all pre-specified patient subgroups, including in patients with or without central nervous system (CNS) metastases. Overall survival data were not mature at the time of the final PFS analysis.

*Confirmed responses

Safety data for Tagrisso in the FLAURA trial were in line with those observed in prior clinical trials. Tagrisso was generally well tolerated, with Grade 3 or higher adverse events (AEs) occurring in 34% of patients taking Tagrisso and 45% in the comparator arm. The most common adverse reactions (≥20%) in patients treated with Tagrisso were diarrhea (58%), rash (58%), dry skin (36%), nail toxicity (35%), stomatitis (29%), fatigue (21%) and decreased appetite (20%).

In the US, Tagrisso is already approved for the 2nd-line treatment of patients with metastatic EGFRm NSCLC, whose disease has progressed on or after a 1st-line EGFR-TKI therapy and who have developed the secondary T790M mutation, as detected by an FDA-approved test. In 2017, Tagrisso was granted Breakthrough Therapy and Priority Review designations by the US FDA in the 1st-line treatment setting. Tagrisso is under regulatory review in the European Union and Japan for use in the 1st-line treatment setting with regulatory decisions anticipated in the second half of 2018.

Tagrisso received its first approval for 1st-line use based on the FLAURA data in Brazil in patients with metastatic EGFRm NSCLC on April 16, 2018.

FDA Approves Tagrisso (osimertinib) as First-Line Treatment for EGFR-Mutated Non-Small Cell Lung Cancer

FDA Approves Intravenous Formulation of Akynzeo (fosnetupitant/palonosetron) for Chemotherapy-Induced Nausea and Vomiting

Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, today announces that the U.S. Food and Drug Administration (FDA) has approved the intravenous formulation of Akynzeo (NEPA, a fixed antiemetic combination of fosnetupitant, 235mg, and palonosetron, 0.25mg) as an alternative treatment option for patients experiencing CINV.

     

The FDA has approved Akynzeo IV (formulation of fosnetupitant first structure  and palonosetron second structure) in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Akynzeo for injection has not been studied for the prevention of nausea and vomiting associated with anthracycline plus cyclophosphamide chemotherapy.

Oral Akynzeo was previously approved by the FDA as a fixed combination oral agent in 2014 for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Akynzeo is an oral fixed combination of palonosetron and netupitant: palonosetron prevents nausea and vomiting during the acute phase and netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.

The bioequivalence of the IV with the oral formulation of netupitant was demonstrated and the safety of IV NEPA was established through a repeated dose safety study in cancer patients to potentially uncover adverse drug reactions that may appear during subsequent clinical practice. No anaphylactic and injection site reactions related to IV NEPA were reported in this study.

Currently a repeated dose safety study is ongoing in patients receiving anthracycline plus cyclophosphamide to further establish the safety profile in this setting.

The prevention of CINV has been refined in treatment guidelines over the past several decades. Currently the combination treatment of antiemetic medicines with different mechanisms of actions are recommended for the prevention of CINV.

The approval of Akynzeo in IV formulation will offer to US patients and healthcare providers an alternative route of administration of the only fixed antiemetic combination targeting two distinct CINV pathways in a single dose.

Riccardo Braglia, Helsinn Group Vice Chairman and CEO, commented: “The approval of the intravenous formulation of Akynzeo paves the way to bring this important therapeutic option to more patients in a new formulation, and we are delighted that we are now able to push ahead with launching this product in the United States in May 2018”

FDA Approves Intravenous Formulation of Akynzeo (fosnetupitant/palonosetron) for Chemotherapy-Induced Nausea and Vomiting

FDA Approves Erleada (apalutamide) for Non-Metastatic Castration-Resistant Prostate Cancer

The U.S. Food and Drug Administration, has approved Erleada (apalutamide) for the treatment of patients with prostate cancer that has not spread (non-metastatic), but that continues to grow despite treatment with hormone therapy (castration-resistant). This is the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer.

“The FDA evaluates a variety of methods that measure a drug’s effect, called endpoints, in the approval of oncology drugs. This approval is the first to use the endpoint of metastasis-free survival, measuring the length of time that tumors did not spread to other parts of the body or that death occurred after starting treatment,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “In the trial supporting approval, Erleada had a robust effect on this endpoint. This demonstrates the agency’s commitment to using novel endpoints to expedite important therapies to the American public."

According to the National Cancer Institute (NCI) at the National Institutes of Health, prostate cancer is the second most common form of cancer in men in the U.S.. The NCI estimates approximately 161,360 men were diagnosed with prostate cancer in 2017, and 26,730 were expected to die of the disease. Approximately 10 to 20 percent of prostate cancer cases are castration-resistant, and up to 16 percent of these patients show no evidence that the cancer has spread at the time of the castration-resistant diagnosis.

Erleada works by blocking the effect of androgens, a type of hormone, on the tumor. These androgens, such as testosterone, can promote tumor growth.

The safety and efficacy of Erleada was based on a randomized clinical trial of 1,207 patients with non-metastatic, castration-resistant prostate cancer. Patients in the trial either received Erleada or a placebo. All patients were also treated with hormone therapy, either with gonadotropin-releasing hormone (GnRH) analog therapy or with surgery to lower the amount of testosterone in their body (surgical castration). The median metastasis-free survival for patients taking Erleada was 40.5 months compared to 16.2 months for patients taking a placebo.

Common side effects of Erleada include fatigue, high blood pressure (hypertension), rash, diarrhea, nausea, weight loss, joint pain (arthralgia), falls, hot flush, decreased appetite, fractures and swelling in the limbs (peripheral edema).

Severe side effects of Erleada include falls, fractures and seizures.

This application was granted Priority Review, under which the FDA’s goal is to take action on an application within 6 months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.

The sponsor for Erleada is the first participant in the FDA’s recently-announced Clinical Data Summary Pilot Program, an effort to provide stakeholders with more usable information on the clinical evidence supporting drug product approvals and more transparency into the FDA’s decision-making process. Soon after approval, certain information from the clinical summary report will post with the Erleada entry on Drugs@FDA and on the new pilot program landing page.

FDA Approves Erleada (apalutamide) for Non-Metastatic Castration-Resistant Prostate Cancer

FDA Approves Symdeko (tezacaftor/ivacaftor and ivacaftor) to Treat Cystic Fibrosis in People Ages 12 and Older with Certain Mutations in the CFTR Gene

Vertex Pharmaceuticals Incorporated announced  the U.S. Food and Drug Administration (FDA) approval of  Symdeko (tezacaftor/ivacaftor and ivacaftor) for treating the underlying cause of cystic fibrosis (CF) in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or who have at least one mutation that is responsive to tezacaftor/ivacaftor. Symdeko is Vertex's third medicine approved to treat the underlying cause of CF. Vertex is ready to launch Symdeko and will begin shipping it to pharmacies in the United States this week.

Ivacaftotezacaftor

"Today is an exciting day for the CF community. The approval of Symdeko, our third disease-modifying CF medicine, offers many patients an important new treatment option," said Jeffrey Leiden, M.D., Ph.D., Vertex's Chairman, President and Chief Executive Officer. "This approval is an important milestone in our journey to treat every person with CF, and we remain committed to urgently advancing our efforts to develop new medicines that treat the underlying cause of CF for the many people still waiting."

In November 2017, the New England Journal of Medicine published the results of two Phase 3 studies of Symdeko. These studies, named EVOLVE and EXPAND, enrolled approximately 750 people with CF ages 12 and older with two copies of the F508del mutation or with one F508del mutation and one mutation that results in residual CFTR function. Across both studies, patients treated with Symdeko experienced statistically significant and clinically meaningful improvements in lung function and other measures of disease, with a favorable safety profile. The most common adverse events, regardless of treatment group, included infective pulmonary exacerbation and cough. The first data from the ongoing EXTEND rollover study, also presented in November, show that the lung function improvements and the safety and tolerability profiles seen in EVOLVE and EXPAND were sustained for up to 48 total weeks of Symdeko treatment.

"We've already seen the significant impact that disease-modifying medicines can have on patients and are incredibly pleased that there is now a third treatment option that enables more patients to benefit from CFTR modulation," said Patrick Flume, M.D., Director of the Medical University of South Carolina Cystic Fibrosis Center and Principal Investigator for the EXTEND study. "In particular, Symdeko is an important treatment option for patients who either never started or discontinued Orkambi, and it also provides increased benefit over Kalydeco alone for patients with residual function mutations."

The European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for the tezacaftor/ivacaftor combination. The company expects approval in the EU in the second half of 2018.

FDA Approves Symdeko (tezacaftor/ivacaftor and ivacaftor) to Treat Cystic Fibrosis in People Ages 12 and Older with Certain Mutations in the CFTR Gene