Alkermes recently announced submission of a new drug application to the FDA for its investigational schizophrenia treatment ALKS 3831, a combination of olanzapine and samidorphan, for the treatment of schizophrenia and the treatment of bipolar I disorder. If approved, the drug is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain.
Adam Simmons, MPH, director of clinical program management at Alkermes, spoke with Healio Psychiatry about the clinical trial results for ALKS 3831 and the impact its approval may have on treatment for patients with schizophrenia or bipolar I disorder. – by Joe Gramigna
Question: Can you provide some background on ALKS 3831?
Answer: ALKS 3831 is an investigational, once-daily oral antipsychotic drug candidate for the treatment of schizophrenia and the treatment of bipolar I disorder. It's composed of samidorphan, which is an opioid receptor antagonist, and olanzapine, which is an effective antipsychotic. The combination of these agents is intended to provide the antipsychotic efficacy of olanzapine while limiting its associated weight gain. We filed an NDA for ALKS 3831 with the FDA for the treatment of schizophrenia and bipolar I disorder in November. Data from the ENLIGHTEN clinical development program for ALKS 3831 was used to support that NDA and it includes two key studies in patients with schizophrenia.
The ENLIGHTEN-1 study evaluated the antipsychotic efficacy of ALKS 3831 compared with placebo over 4 weeks. In that study, ALKS 3831 demonstrated statistically significant reductions from baseline Positive and Negative Syndrome Scale (PANSS) scores at 4 weeks in comparison to the placebo arm. The olanzapine arm in that study achieved similar improvements from baseline PANSS scores compared to placebo.
This year at the American College of Neuropsychopharmacology annual meeting, we presented the results of ENLIGHTEN-2, in which we assessed weight gain with ALKS 3831 compared with olanzapine alone over the course of 6 months. We demonstrated statistically significant improvements compared with olanzapine at 6 months for both the co-primary endpoints, one of those being percent change in baseline weight gain and the second one being the proportion of people who gained 10% or more of their baseline body weight. We also achieved statistical significance on the secondary endpoint, with the ALKS 3831 treatment group demonstrating a lower proportion of people who gained 7% or more of their baseline body weight.
Q: How does ALKS 3831 mitigate weight gain in these patient populations?
A: The mechanism of action of the investigational drug ALKS 3831 has not been determined. ALKS 3831 was designed to provide the antipsychotic efficacy of olanzapine while limiting olanzapine-associated weight gain, which is a serious side effect. In preclinical and clinical studies, researchers provided evidence for the critical role of the opioid system in mediating food reward, feeding behavior and metabolism, but we haven't determined the mechanism of action specific to ALKS 3831.
Q: If the drug is approved, is there anything specific clinicians should know?
A: If approved, ALKS 3831 would be an important addition to treatment options available to clinicians. We look forward to working with the FDA over the coming year to bring this potential new medication to approval.
Q: How might its approval impact treatment of these patient populations?
A: There's a significant unmet patient need that remains in schizophrenia and bipolar I disorder despite the number of treatment options that are available. Patients deserve new treatment options that don't sacrifice tolerability for efficacy.
Hopefully, we'll be able to offer another additional treatment option for clinicians in the treatment of schizophrenia and bipolar I disorder.
Disclosures: Simmons is employed by Alkermes.