A Comprehensive Pharmacological and Clinical Review of Samidorphan Combination Therapies: Olanzapine/Samidorphan (LYBALVI™) and Buprenorphine/Samidorphan (ALKS 5461)

Introduction

This report provides a comprehensive analysis of combination therapies involving samidorphan, a novel opioid antagonist. The initial query specified an interest in the combination of "buprenorphine hydrochloride;samidorphan." It is critical to clarify at the outset that this formulation, known by its developmental code ALKS 5461, was an investigational agent for major depressive disorder that was ultimately not approved for marketing by the U.S. Food and Drug Administration (FDA).[1] In contrast, a different combination product, olanzapine and samidorphan, has successfully navigated the regulatory process and is currently marketed under the brand name LYBALVI™. This therapy is FDA-approved for the treatment of schizophrenia and bipolar I disorder in adults.[4]

To provide a complete and clinically relevant assessment, this report is structured in two parts. Part I delivers an exhaustive review of the approved product, LYBALVI™, covering its regulatory status, pharmacology, clinical trial data, and safety profile. This section addresses the practical application of samidorphan in current medical practice. Part II examines the developmental history and regulatory failure of the investigational agent ALKS 5461. This analysis provides essential context on the scientific rationale and clinical challenges that led to its non-approval.