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A Structured Benefit-Risk Assessment to Evaluate a Combination of Olanzapine and Samidorphan for the Treatment of Schizophrenia and Bipolar I Disorder

Published online by Cambridge University Press:  28 April 2022

Brittany D. Roy
Affiliation:
Alkermes, Inc., Waltham, MA, USA
David McDonnell
Affiliation:
Alkermes Pharma Ireland Limited, Dublin, Ireland
Bei Yu
Affiliation:
Alkermes, Inc., Waltham, MA, USA
Christine Graham
Affiliation:
Alkermes, Inc., Waltham, MA, USA
Ying Jiang
Affiliation:
Alkermes, Inc., Waltham, MA, USA
Sergey Yagoda
Affiliation:
Alkermes, Inc., Waltham, MA, USA
Vasudev Bhupathi
Affiliation:
Alkermes, Inc., Waltham, MA, USA
Lauren DiPetrillo
Affiliation:
Alkermes, Inc., Waltham, MA, USA
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Abstract

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Background

A combination of olanzapine and samidorphan (OLZ/SAM) that provides the efficacy of olanzapine while mitigating weight gain was recently approved by the FDA for the treatment of schizophrenia and bipolar I disorder. To improve communication of the OLZ/SAM benefit-risk profile, a structured framework was utilized.

Methods

The Benefit-Risk Action Team framework was used to evaluate OLZ/SAM, with analyses completed for each pivotal study. ENLIGHTEN-1 evaluated antipsychotic efficacy and safety. ENLIGHTEN-2 evaluated the weight profile of OLZ/SAM vs olanzapine. Benefit-risk outcomes were selected based on study outcome parameters, known risks of olanzapine and samidorphan, and public health importance. A subset of opioid antagonist risks was not assessed due to clinical trial exclusions; however, they were factored into the overall evaluation. Risk differences and confidence intervals were analyzed.

Results

In ENLIGHTEN-1, OLZ/SAM had a lower risk of psychiatric discontinuation and nonresponse to treatment compared with placebo; higher risks of hyperprolactinemia, weight gain (≥7%), sedation, and worsening of fasting triglycerides and glucose, and no difference for fasting total and LDL cholesterol, neutropenia, orthostatic hypotension, and movement disorders. In ENLIGHTEN-2, OLZ/SAM had reduced risks of weight gain and waist circumference increase compared to olanzapine along with similar risks of relapse and psychiatric discontinuation and no difference in metabolic worsening, neutropenia, hyperprolactinemia, orthostatic hypotension, sedation, and movement disorders.

Discussion

Based on this assessment, OLZ/SAM has comparable efficacy and a safety profile consistent with olanzapine, with reduced weight gain. A structured approach to assessing the benefit-risk profile of a product facilitates transparent evaluation and communication.

Funding

Alkermes, Inc.

Type
Abstracts
Copyright
© The Author(s), 2022. Published by Cambridge University Press