New Drug Application for Olanzapine/Samidorphan Expanded to Include Bipolar I

July 23, 2019
Julie Bowen

The novel combination drug is designed to mitigate the weight gain associated with olanzapine.

NEWS BRIEF

Alkermes plans to expand its New Drug Application (NDA) for olanzapine/samidorphan (ALKS 3831) to include treatment of bipolar I disorder in addition to schizophrenia. The novel combination drug is designed to provide the efficacy of olanzapine while mitigating the weight gain associated with the atypical antipsychotic.1

“Olanzapine is one of the most effective antipsychotics,” writes Brian Miller, MD, PhD, MPH, Associate Professor of Psychiatry, Augusta University, Georgia, in Psychiatric Times. “However, the adverse metabolic effects of olanzapine have limited its clinical utility.”2

ENLIGHTEN data

The ALKS 3831 NDA, which Alkermes plans to submit in the fourth quarter of 2019, will include data from the completed ALKS 3831 ENLIGHTEN clinical development program in patients with schizophrenia as well as pharmacokinetic bridging data comparing ALKS 3831 and ZYPREXA® (olanzapine).

ENLIGHTEN-2 is a multicenter, double-blind, randomized phase 3 study that compared the weight gain profile of ALKS 3831 with that of olanzapine over 6 months in 561 patients with stable schizophrenia. Alkermes announced the topline results in a press release in November 2018.

Patients who received olanzapine (n=272) had a 57% higher mean percent weight change at 6 months compared with those who received ALKS 3831 (n=266), (6.59% for olanzapine versus 4.21% for ALKS 3831, P=.003). The proportion of patients who gained 10% or more of their baseline body weight was 29.8% for olanzapine versus 17.8% for ALKS 3831 (P=.003). Thus, patients in the olanzapine treatment group had two times the risk of gaining 10% or more of their baseline body weight at 6 months compared with those who received ALKS 3831.3

Proposed indications

The ALKS 3831 NDA will include data to support an indication for the treatment of manic or mixed episodes associated with bipolar I disorder as a monotherapy or adjunct to lithium or valproate and for maintenance treatment of bipolar I disorder; and an indication for the treatment of schizophrenia. The proposed fixed dosage strengths for ALKS 3831 include 10 mg of samidorphan co-formulated with 5 mg, 10 mg, 15 mg, or 20 mg of olanzapine.

“Bipolar I disorder is a complicated and often misdiagnosed disease, characterized by severe shifts in mood and energy that can impact a person’s ability to complete day-to-day activities. Antipsychotics are a mainstay treatment option for many people living with bipolar I disorder; however, new treatments with differentiated efficacy and tolerability profiles are needed,” said Roger S. McIntyre, MD, Professor of Psychiatry and Pharmacology at the University of Toronto, and Head of the Mood Disorders Psychopharmacology Unit at the University Health Network in Toronto, Canada, in a press statement. “A potential new medication like ALKS 3831 would be a meaningful addition to the bipolar I disorder treatment landscape.”

References:

1. Alkermes expands planned New Drug Application for ALKS 3831 to include treatment of bipolar I disorder [press release]. Dublin, Ireland: Alkermes plc; July 15, 2019.

2. Miller B. Mitigation of olanzapine-induced weight gain: not the sami old thing. Psychiatric Times. May 3, 2019. Accessed July 19, 2019.

3. Alkermes announces positive topline results from ENLIGHTEN-2 phase 3 study of ALKS 3831 in patients with schizophrenia [press release]. Dublin, Ireland: Alkermes plc; November 29, 2018.