Meeting News

ALKS 5461 well-tolerated in major depression

Michael Thase
Michael E. Thase
 

ALKS 5461, an investigational opioid system modulator that combines buprenorphine and samidorphan, showed antidepressant effects for up to 52 weeks of treatment in patients with major depressive disorder, according to data presented at the 2018 American Society of Clinical Psychopharmacology annual meeting.

“There is a great unmet need for novel mechanisms that treat depression in ways different than conventional medications that target serotonin or norepinephrine,” Michael E. Thase, MD, professor of psychiatry at University of Pennsylvania Perelman School of Medicine, told Healio Psychiatry.

“Humans have used opiates for centuries to ‘mellow’ bad moods, but of course the abuse liability of this approach has prevented therapeutic applications,” he continued. “The research program for this compound has included a number of double blind studies, of which two are unequivocally positive; these data are being reviewed by the FDA for a possible indication as an adjunct to antidepressants.”

In a previous study, ALKS 5461 has shown efficacy compared with placebo as an adjunctive treatment for MDD. At the meeting, Thase presented data on the long-term efficacy, safety and tolerability of ALKS 5461 from an ongoing, 1-year, open-label extension study.

Patients with MDD and a history of inadequate response to standard antidepressant therapy, some of whom were also participants from one of the short-term FORWARD studies, received sublingual ALKS 5461 2 mg buprenorphine/2 mg samidorphan as adjunct treatment for up to 52 weeks. The researchers evaluated participants’ change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS-10) as well as time to remission using Kaplan-Meier methods. Safety, suicidal ideation or behavior and withdrawal symptoms were also examined.

Overall, ALKS 5461 was well-tolerated. Of 1,454 enrolled patients, 49% completed the study and 11% discontinued due to an adverse event. Thase and colleagues found mean depression scores decreased from baseline and remained lower until the study ended. At 12 months, 52.5% of patients had remitted and the median time to remission was 59 days, according to the results.

“In the longer-term follow-up, there was no suggestion of tolerance of therapeutic effects (ie, the benefit was durable), the side effect profile was generally comparable to standard medications with no significant late appearing side effects, and when it was time to stop the experimental medication, there was essentially no hint whatsoever of opiate-like withdrawal or discontinuation symptoms,” Thase told Healio Psychiatry.

Adverse events typically occurred when patients started ALKS 5461 and resolved as they continued treatment. Events that occurred at a frequency of at least 5% included nausea, headache, constipation, dizziness, somnolence, vomiting, dry mouth, fatigue, upper respiratory infection, insomnia, nasopharyngitis, sedation and hyperhidrosis. The researchers did not observe increased risk for suicidal ideation or behavior; withdrawal was uncommon and not very severe. – by Savannah Demko

References:

Thase ME, et al. Abstract W34. Presented at: American Society of Clinical Psychopharmacology Annual Meeting; May 29-June 1, 2018; Miami Beach, Florida.

Disclosures: Thase is a consultant for Alkermes and reports research grants from the company.

Michael Thase
Michael E. Thase
 

ALKS 5461, an investigational opioid system modulator that combines buprenorphine and samidorphan, showed antidepressant effects for up to 52 weeks of treatment in patients with major depressive disorder, according to data presented at the 2018 American Society of Clinical Psychopharmacology annual meeting.

“There is a great unmet need for novel mechanisms that treat depression in ways different than conventional medications that target serotonin or norepinephrine,” Michael E. Thase, MD, professor of psychiatry at University of Pennsylvania Perelman School of Medicine, told Healio Psychiatry.

“Humans have used opiates for centuries to ‘mellow’ bad moods, but of course the abuse liability of this approach has prevented therapeutic applications,” he continued. “The research program for this compound has included a number of double blind studies, of which two are unequivocally positive; these data are being reviewed by the FDA for a possible indication as an adjunct to antidepressants.”

In a previous study, ALKS 5461 has shown efficacy compared with placebo as an adjunctive treatment for MDD. At the meeting, Thase presented data on the long-term efficacy, safety and tolerability of ALKS 5461 from an ongoing, 1-year, open-label extension study.

Patients with MDD and a history of inadequate response to standard antidepressant therapy, some of whom were also participants from one of the short-term FORWARD studies, received sublingual ALKS 5461 2 mg buprenorphine/2 mg samidorphan as adjunct treatment for up to 52 weeks. The researchers evaluated participants’ change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS-10) as well as time to remission using Kaplan-Meier methods. Safety, suicidal ideation or behavior and withdrawal symptoms were also examined.

Overall, ALKS 5461 was well-tolerated. Of 1,454 enrolled patients, 49% completed the study and 11% discontinued due to an adverse event. Thase and colleagues found mean depression scores decreased from baseline and remained lower until the study ended. At 12 months, 52.5% of patients had remitted and the median time to remission was 59 days, according to the results.

“In the longer-term follow-up, there was no suggestion of tolerance of therapeutic effects (ie, the benefit was durable), the side effect profile was generally comparable to standard medications with no significant late appearing side effects, and when it was time to stop the experimental medication, there was essentially no hint whatsoever of opiate-like withdrawal or discontinuation symptoms,” Thase told Healio Psychiatry.

Adverse events typically occurred when patients started ALKS 5461 and resolved as they continued treatment. Events that occurred at a frequency of at least 5% included nausea, headache, constipation, dizziness, somnolence, vomiting, dry mouth, fatigue, upper respiratory infection, insomnia, nasopharyngitis, sedation and hyperhidrosis. The researchers did not observe increased risk for suicidal ideation or behavior; withdrawal was uncommon and not very severe. – by Savannah Demko

References:

Thase ME, et al. Abstract W34. Presented at: American Society of Clinical Psychopharmacology Annual Meeting; May 29-June 1, 2018; Miami Beach, Florida.

Disclosures: Thase is a consultant for Alkermes and reports research grants from the company.