FDA Approves Auvelity (dextromethorphan and bupropion) for the Treatment of Major Depressive Disorder in Adults

 

        

dextromethorphan

 

Bupropion

In continuation of my updates on dextromethorphan and Bupropion, 

Axsome Therapeutics, Inc. , a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders,  announced  the U.S. Food and Drug Administration (FDA)  approval of  Auvelity (dextromethorphan HBr -bupropion HCl) extended-release tablets for the treatment of major depressive disorder (MDD) in adults.¹ Auvelity is the first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week.  The rapid antidepressant effects of Auvelity were sustained at all subsequent timepoints. Auvelity is the first and only oral N-methyl D-aspartate (NMDA) receptor antagonist approved for the treatment of MDD.  Axsome anticipates Auvelity to be commercially available in the U.S. in the fourth quarter of 2022.

Maurizio Fava, MD, Psychiatrist-In-Chief, Department of Psychiatry, Massachusetts General Hospital, Executive Director, Clinical Trials Network & Institute, Associate Dean for Clinical & Translational Research, and Slater Family Professor of Psychiatry, Harvard Medical School said, “The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile. Auvelity, which was granted Breakthrough Therapy designation by the FDA, represents the first new oral non-monoamine-based mechanism of action approved to treat major depressive disorder in over sixty years. Nearly two thirds of patients treated with currently available antidepressants do not adequately respond, and those that do may not achieve clinically meaningful responses for up to six to eight weeks. Given the debilitating nature of depression, the efficacy of Auvelity observed at one week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition.”

Michael Pollock, Chief Executive Officer of the Depression and Bipolar Support Alliance (DBSA), a leading national patient advocacy organization focusing on depression and bipolar disorder said, “The mental health crisis in the United States is one of the most pressing health issues facing our country today. Over 20 million American adults experienced major depressive disorder each year prior to the COVID-19 pandemic. These numbers increased dramatically during the pandemic with approximately thirty percent of adults in the U.S. or more than 80 million Americans experiencing elevated symptoms of depression. The need for new treatment options, particularly those with new mechanisms of action, could not be clearer and more urgent for those living with, or impacted by, major depressive disorder.”

Dan V. Iosifescu, MD, Professor of Psychiatry at the New York University School of Medicine, and Director of the Clinical Research Division at the Nathan Kline Institute for Psychiatric Research said, “Major depressive disorder is disabling and potentially life-threatening, causes profound distress for patients and their families, and leads to substantial healthcare resource utilization. Auvelity’s oral NMDA receptor antagonist and sigma-1 receptor agonist activity, which targets glutamatergic neurotransmission, provides clinicians a long sought after new mechanistic approach which may benefit the millions of patients living with this serious condition. In clinical trials, Auvelity has demonstrated rapid and statistically significant improvement in depressive symptoms as early as Week 1, and increased rates of remission at Week 2 compared with placebo. This early benefit with Auvelity was maintained and increased with continued treatment, and was accompanied by a favorable safety and tolerability profile.”

Auvelity was studied in a comprehensive clinical program which included more than 1,100 patients with depression. The efficacy of Auvelity in the treatment of MDD was demonstrated in the GEMINI placebo-controlled study, and confirmatory evidence which included the ASCEND study comparing Auvelity to bupropion sustained-release tablets. In the GEMENI study, Auvelity was statistically significantly superior to placebo in improvement of depressive symptoms as measured by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6, the study’s primary endpoint. To evaluate speed of onset of action, the change in MADRS total score from baseline to Week 1 and from baseline to Week 2 were pre-specified secondary efficacy endpoints. The difference between Auvelity and placebo in change from baseline in MADRS total score was statistically significant at Week 1 and at Week 2.¹ In the ASCEND study, Auvelity was statistically significantly superior to bupropion sustained-release tablets 105 mg twice daily on the primary outcome measure.⁵ The primary outcome measure of the ASCEND study was calculated by assessing the change from baseline in MADRS total scores from Week 1 to Week 6 and then taking the average of those scores.¹ In the placebo-controlled clinical study, the most common (incidence ≥5% for Auvelity and more than twice as frequently as placebo) adverse reactions were dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.¹

The FDA granted Breakthrough Therapy designation for Auvelity for the treatment of MDD in March 2019. This designation is granted to candidate drugs that show potential for benefit above that of available therapies based on preliminary clinical data, and it provides the sponsor with added focus from and greater interactions with FDA staff during the development of the candidate drug.⁶ The Auvelity New Drug Application (NDA) was evaluated by the FDA under Priority Review, which is granted by the FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.

 

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

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

 

Diet Drugs: Which Ones Work?

Any of the prescription weight-loss drugs on the market can help obese people shed pounds, although some seem more effective than others, a new study finds.

Currently, five drugs are approved in the United States for managing obesity. But little has been known about how they stack up against one another, said Dr. Siddharth Singh, the lead researcher on the new study.

The findings  based on more than 29,000 people in total show all five drugs can work. But people on certain drugs tended to be more successful, at least over one year.

Specifically, people using Qsymia (phentermine-topiramate) or Victoza (liraglutide) had the highest odds of shedding at least 5 percent of their initial weight. Those taking Xenical (orlistat) had the lowest odds.

phentermine liraglutide

 orlistat  lorcaserin

 Bupropion/naltrexone 

However, there is no single drug that's "best" for everyone, stressed Singh, an assistant clinical professor at the University of California, San Diego.

He cautioned that his team's numbers are just averages across study groups. Plus, he said, the side effects of each medication vary, and that is an important factor in treatment decisions.

"Obesity treatment always needs to be personalized," Singh said.

Nikhil Dhurandhar, a spokesman for the Obesity Society, agreed that people respond differently to any given weight-loss drug.

"In general, if you give drug 'X,' there will be a wide variation in patients' responses," said Dhurandhar, who is also a professor of nutritional sciences at Texas Tech University in Lubbock. He wasn't involved in the study.

Some people will have "zero" weight loss   or even gain weight -- while others will see the pounds drop off, Dhurandhar said.

He also stressed that there is no such thing as a magic weight-loss pill.

"These drugs can help you eat less through effects on appetite," Dhurandhar explained. "But you have to change your diet and get regular exercise."

"Medications are supplements, not substitutes, to your efforts," he said.

For the study, Singh's team analyzed findings from 28 clinical trials testing the five approved drugs for obesity: Qsymia, Victoza and Xenical, along with Belviq (lorcaserin) and Contrave (naltrexone-bupropion).

On average, the researchers found, each drug worked better than a placebo in helping obese adults lose weight over a year. But certain medications seemed more effective than others.

People on Qsymia typically lost the most weight -- almost 20 pounds more, versus study patients given placebo pills. They were also nine times more likely to drop at least 5 percent of their initial weight, the researchers found.

People taking Xenical or Belviq tended to shed the fewest pounds -- 6 to 7 pounds more than placebo users. Contrave and Victoza patients typically lost 11 to 12 pounds more, compared with placebo.

But not everyone benefited. In studies of all of the drugs, Singh noted, a significant number of people dropped out because of side effects.

And those dropouts were more common with certain medications, the study found. People taking Contrave or Victoza were almost three times more likely to quit a trial over side effects, compared with placebo users. According to Victoza's maker, the drug can cause inflammation of the pancreas or kidney problems.

Just as people vary in their weight-loss success with any given drug, their risks of side effects will differ, too, Singh said.

He pointed to Contrave as an example. Because it contains the antidepressant bupropion, it carries a boxed warning about the potential risk of suicidal thoughts. So it might not be the best choice for someone with psychiatric conditions that could make them more vulnerable, Singh said.

Victoza, meanwhile, is an injection drug prescribed for controlling high blood sugar in people with type 2 diabetes. So if a patient needs medication for diabetes as well as weight loss, Victoza might be a good option, Singh said.

Most of the medications have been approved only in the past few years, so one question is whether they maintain their effects over the long run, Singh said.

"We do need more long-term data," Dhurandhar agreed.

Still, he said, medications are an important option for managing obesity. And if one does not work, Dhurandhar added, he'd recommend trying another.

Antidepressant Wellbutrin linked to long-term modest weight loss

Group Health researchers have found that bupropion (marketed as Wellbutrin) is the only antidepressant that tends to be linked to long-term modest weight loss.

Previously, Group Health researchers showed a two-way street between depression and body weight: People with depression are more likely to be overweight, and vice versa. These researchers also found that most antidepressant medications have been linked to weight gain.

Prior research on antidepressants and weight change was limited to one year or shorter. But many people take antidepressants--the most commonly prescribed medications in the United States--for longer than a year. So for up to two years the new study followed more than 5,000 Group Health patients who started taking an antidepressant. TheJournal of Clinical Medicine published it: "Long-Term Weight Change after Initiating Second-Generation Antidepressants."

"Our study suggests that bupropion is the best initial choice of antidepressant for the vast majority of Americans who have depression and are overweight or obese," said study leader David Arterburn, MD, MPH. He's a senior investigator at Group Health Research Institute (GHRI), a Group Health physician, and an affiliate associate professor in the University of Washington (UW) School of Medicine's Department of Medicine. But in some cases, an overweight or obese patient has reasons why bupropion is not for them--like a history of seizure disorder--and it would be better for them to choose a different treatment option.

FDA Approves New Obesity Drug Contrave

In continuation of my update on Contrave

The U.S. Food and Drug Administration's approval of a new weight-loss drug on Wednesday marks the third time the agency has given its blessing to a new diet medication since 2012.

Called Contrave, the medicine is a combination of two approved drugs: naltrexone, which treats alcohol and drug addiction, and bupropion, which treats depression and seasonal affective disorder and is used to help smokers quit.

The agency said in a news release that Contrave can be used by obese adults and by overweight adults who have at least one other weight-related condition or illness, such as high blood pressure or type 2 diabetes.

According to the U.S. Centers for Disease Control and Prevention, more than one-third of adults in the United States are obese, the FDA said in its news release.

"Obesity continues to be a major public health concern," said Dr. Jean-Marc Guettier, director of the division of metabolism and endocrinology products in the FDA's Center for Drug Evaluation and Research. "When used as directed in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, Contrave provides another treatment option for chronic weight management."

FDA Approves New Obesity Drug Contrave  

FDA Approves Contrave (bupropion/naltrexone) for Weight Management

In continuation of my update on bupropion/naltrexone

The U.S. Food and Drug Administration today approved Contrave (naltrexone hydrochloride and bupropion hydrochloride extended-release tablets) as treatment option for chronic weight management in addition to a reduced-calorie diet and physical activity.

FDA Approves Contrave (bupropion/naltrexone) for Weight Management

FDA accepts Orexigen's Contrave NDA for treatment of obesity

Orexigen Therapeutics, Inc., a biopharmaceutical company focused on the treatment of obesity, recently anounced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company's New Drug Application (NDA) for Contrave(R) (see structrures below ; naltrexone SR   and bupropion SR), its investigational drug for the treatment of obesity. The NDA is based on a substantial body of evidence gathered through the Contrave Obesity Research (COR) clinical program, which included over 4,500 patients.....

"We are pleased the FDA has accepted our NDA for filing and look forward to working with the Agency during the review process," said Michael Narachi, President and CEO of Orexigen. "If approved, we believe Contrave will become an important therapeutic option for obese patients, making weight loss and weight maintenance an achievable cornerstone in the treatment of obesity and its common co-morbidities."

Ref : http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irol-newsArticle&ID=1432740&highlight=