The combination treatment of olanzapine and samidorphan (ALKS 3831, Alkermes) was found to be associated with significantly less weight gain and smaller increases in waist circumference than treatment with olanzapine alone, according to a recent study published in the American Journal of Psychiatry.1

Additionally, the results demonstrated that the combination treatment had an antipsychotic efficacy similar to that of olanzapine monotherapy and was well tolerated by patients.1 Following these results, an advisory committee panel has been scheduled to review the new drug application (NDA) for the combination treatment, with the Prescription Drug User Fee Act action date set for November 15, 2020.2

"The publication of the ENLIGHTEN-2 data in a peer-reviewed journal represents an important milestone for the ALKS 3831 development program and demonstrates Alkermes' dedication to expanding the body of research on schizophrenia treatment," said Craig Hopkinson, MD, executive vice president of research and development and chief medical officer at Alkermes, in a press release.3

The 6-month, phase 3 ENLIGHTEN-2 clinical trial focused on the combination treatment’s weight gain profile compared with olanzapine in 561 patients with stable schizophrenia.1,3 Of the 561 patients included in the study, 538 had at least 1 postbaseline weight assessment conducted.3

By week 24, the researchers observed that the least squares mean percent weight change from baseline was 4.21% in the olanzapine and samidorphan group. In the olanzapine group, the weight change from baseline was 6.59%. According to the researchers, the difference of 2.38% between the 2 groups was significant.1

Additionally, 27.5% of patients given the combination treatment experienced weight gain, whereas 42.7% of the olanzapine group experienced weight gain.1

Increases in waist circumference were also found to be less significant in the combination treatment group compared with the olanzapine group, whereas the improvement of schizophrenia symptoms remained similar among both treatment groups.1

Following the results from this trial, findings from the prior ENLIGHTEN-1 trial, and data from 27 other clinical studies assessing olanzapine and samidorphan, a joint meeting of the FDA’s Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee has been scheduled for October 9, 2020, to review the NDA for the combination treatment.2 The advisory committee panel plans to assess the efficacy, safety, and benefit-risk profile of the treatment for schizophrenia and bipolar I disorder.2

According to the press release, the advisory panel is expected to focus on the clinical meaningfulness of the combination treatment’s management of the weight gain associated with olanzapine use, including the magnitude of weight effect and the impact of the treatment on laboratory-based metabolic parameters. However, the panel has explained it will also assess potential clinical risks related to the interaction of the combination treatment—which includes the opioid receptor antagonist samidorphan—and opioids for patients.2

“We look forward to engaging with members of the joint advisory committee panel in a robust discussion of the clinical evidence for ALKS 3831,” Hopkinson said in the press release. “For adults living with schizophrenia or bipolar I disorder, populations already prone to shortened life expectancy and cardiovascular comorbidities, the significant weight gain often associated with olanzapine can represent a major clinical liability. Patients and healthcare providers may benefit from additional treatment options that help manage disease symptoms while mitigating weight gain. We are committed to bringing this potential new medicine to adults living with schizophrenia or bipolar I disorder.”2 

REFERENCES
  1. Correl C, Newcomer J, Silverman B, et al. Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study. American Journal of Psychiatry. 2020. doi: 10.1176/appi.ajp.2020.19121279.
  2. Virtual FDA Advisory Committee Meeting to Review New Drug Application for ALKS 3831 for Treatment of Schizophrenia and Bipolar I Disorder Tentatively Scheduled for Oct. 9, 2020. Dublin, Ireland: Alkermes; August 21, 2020. investor.alkermes.com/news-releases/news-release-details/virtual-fda-advisory-committee-meeting-review-new-drug. Accessed September 23, 2020.
  3. American Journal of Psychiatry Publishes Data From Alkermes' Phase 3 ENLIGHTEN-2 Weight Study of ALKS 3831 in Patients With Schizophrenia. Dublin, Ireland: Alkermes; August 17, 2020. investor.alkermes.com/news-releases/news-release-details/american-journal-psychiatry-publishes-data-alkermes-phase-3. Accessed September 23, 2020.