A joint panel of the Food and Drug Administration voted Nov. 1 against approving a new opioid-containing drug as an adjunctive treatment for major depressive disorder.
The 21-2 vote against approval by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based on concerns that the drug’s benefit-risk profile was not strong enough to warrant approval, according to a press release from Alkermes, developer of the drug, which is a combination of buprenorphine and samidorphan known as ALKS 5461.
“We were disappointed and surprised by the FDA’s characterization of the safety and efficacy data for ALKS 5461 and the resulting outcome of the advisory committee vote, particularly for the patients, their families and treatment providers who need and deserve access to novel therapies that work differently than currently available antidepressants, Richard Pops, chief executive officer of Alkermes, said in the release. “We remain steadfast in our commitment to make a meaningful difference in the lives of people suffering with serious mental health conditions, and will continue to work with the FDA as it completes its review of the ALKS 5461 regulatory submission.”
At the meeting, Sanjay J. Mathew, MD, a psychiatrist affiliated with the Baylor College of Medicine in Houston and a consultant for Alkermes who was paid for his time and travel to the meeting, discussed which patients might be good candidates for the new drug. He used an example of a patient who had failed on several monotherapies and would consider augmentation with a second drug. “In my view, this drug has a positive benefit-risk profile with a comparable efficacy” to currently available drugs, but with a new distinct mechanism that appears not to have certain undesirable side effects such as weight gain and sleepiness, he said.
Meanwhile, representatives from Alkermes discussed phase 3 studies, in which adults with treatment-resistant major depressive disorder were randomized to BUP/SAM in doses of 1mg/1mg or 2mg/2mg, or a placebo. In the trial, known as Study 207, changes in the MADRAS-10 total scores were significantly higher in the 2mg/2mg treatment groups, compared with placebo when data from 5 weeks and 6 weeks of treatment were combined.
However, in the FDA’s review of the data, it was noted that the efficacy was based on the MADRAS-10 average vs. the MADRAS-10 end of treatment, and the average “tends to obscure a possible drop-off in drug efficacy after the first few weeks of treatment.”
The FDA usually follows its panels’ recommendations, which are not binding.