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OLANZAPINE AND SAMIDORPHAN IN ADULTS WITH SCHIZOPHRENIA OR BIPOLAR I DISORDER: UPDATED REVIEW OF CLINICAL DATA

Leslie Citrome — Christoph U. Correll2, Roger S. McIntyre3, Mark S. Todtenkopf4, Christina Arevalo4, James A. McGrory4, David McDonnell5 1New York Medical College, Valhalla, NY, USA, 2Zucker Hillside Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, The Feinstein Institute for Medical Research, Center for Psychiatric Neuroscience, Northwell Health, Charité Universitätsmedizin, German Center for Mental Health (DZPG), 3University of Toronto, 4Alkermes, Inc., 5Alkermes Pharma Ireland Ltd.

2026 ASCP Annual Meeting

Background

Combined olanzapine and samidorphan (OLZ/SAM) received US FDA approval in 2021 for the treatment of adults with schizophrenia or bipolar I disorder (BD-I) and was accompanied by a clinical data review summarizing OLZ/SAM’s efficacy and safety. The key highlight was that OLZ/SAM provides the established antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain.

Methods

This updated review synthesizes the following clinical studies/analyses conducted over the past 5 years, providing a comprehensive overview of the OLZ/SAM clinical program. Effectiveness, safety, and tolerability of OLZ/SAM were assessed in a 12-week randomized double-blind study conducted in early-in-illness patients, a population at risk of antipsychoticassociated weight gain. A 4-year open-label extension study and subgroup analysis evaluated long-term safety and durability of treatment effect of OLZ/SAM in patients who completed prior studies. An individual patient data meta-analysis compared effects of OLZ/SAM versus olanzapine on weight gain using data from 3 clinical trials. A post hoc analysis explored effects of OLZ/SAM treatment on negative symptoms in patients with an acute exacerbation of schizophrenia. Patient retention rates were also summarized across the OLZ/SAM phase 3 clinical program.

Results

OLZ/SAM treatment was associated with a durable antipsychotic treatment effect, clinically meaningful and durable improvement from baseline in the negative symptoms of schizophrenia, and minimal weight gain and metabolic changes for up to 5 years. Treatment with OLZ/SAM was well tolerated, and substantial retention rates were observed.

Conclusion

These data reinforce OLZ/SAM as a valuable long-term treatment option for patients with schizophrenia or BD-I. This study was funded by Alkermes, Inc. Medical writing and editorial support were provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Alkermes, Inc.