Olanzapine and samidorphan combination effective for long-term treatment of schizophrenia, bipolar disorder

The topline results of the long-term safety study were announced by the biopharmaceutical company Alkermes. The findings suggest that the use of LYBALVI was generally well-tolerated with stability of body weight and metabolic profile and durable symptom control for up to 4 years of treatment.

LYBALVI is already approved in the U.S. for the treatment of adults with schizophrenia, and for the treatment of adults with bipolar I disorder, as a maintenance monotherapy or for the acute treatment of manic or mixed episodes, as monotherapy or as an adjunct to lithium or valproate.

"We are pleased to share the topline results from this long-term, open-label study. These data highlight the potential utility of LYBALVI as a foundational maintenance treatment option for people living with schizophrenia or bipolar I disorder and reinforce the safety profile of LYBALVI established in previous studies," said Craig Hopkinson, M.D., Executive Vice President, Research & Development and Chief Medical Officer at Alkermes.

"In this study, patients taking LYBALVI experienced sustained treatment effect and tolerability, including stability across multiple metabolic parameters. Against the backdrop of average treatment persistency of less than six months for oral atypical antipsychotics generally, we are encouraged that more than one-third of subjects completed four years of treatment with LYBALVI."

For inclusion in the long-term safety study, participants were required to have been enrolled in 1 of the three antecedent phase 3 clinical studies evaluating olanzapine and samidorphan: the ENLIGHTEN-1 safety extension study, the ENLIGHTEN-2 safety extension study, and the 12-week ENLIGHTEN-Early randomized control trial comparing LYBALVI to olanzapine.1

Five hundred twenty-three participants received ≥ 1 dose of LYBALVI, comprising 5 – 20 mg of olanzapine and 10 mg of samidorphan. The study had a mean age of 35.1 years, 61.6% were male, and 72.7% were White.

The global, open-label extension study involved 523 participants who received at least one dose of LYBALVI and 35.9% of participants completed the four-year treatment period.

The key findings of the trial are as follows:

• The safety profile of LYBALVI was consistent with previous studies. Patients' symptoms of bipolar I disorder or schizophrenia remained stable with up to four years of treatment with LYBALVI, as measured by the Clinical Global Impression of Severity (CGI-S) scale (mean change from baseline in CGI-S score of -0.28).
• Long-term treatment with LYBALVI was associated with minimal changes in body weight (mean change from baseline of +1.47 kg) and waist circumference (observed mean change from baseline of +0.61 cm) with up to four years of treatment.
• There were generally minimal changes in lipid and glycemic parameters, including LDL cholesterol, HDL cholesterol, fasting glucose, triglycerides, and HbA1c over the measured period.
• 60% of patients reported an adverse event (AE).
• The most common AEs reported (>5%) were weight gain, headache, anxiety, insomnia, somnolence, nausea and weight decrease; most AEs were mild to moderate in severity.

"As clinicians, we see firsthand the challenges that people living with complex mental health conditions may face in finding treatment options that work for them long term, in terms of both efficacy and tolerability," said Jacob S. Ballon, M.D., M.P.H., Clinical Professor of Psychiatry and Behavioral Sciences at Stanford University and a study investigator.

"These data, which demonstrated long-term tolerability and symptom control, as well as stability across key weight and metabolic factors, underscore LYBALVI's established safety and efficacy profile and provide important information for clinicians as we navigate treatment decisions with our patients in the real world."