Topline results from long-term, open-label safety and duralility of treatment effect study of Lybalvi (olanzapine and samidorphan) in patients with schizophrenia, schizophreniform disorder or bipolar I disorder

Lybalvi is 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 adjunct to lithium or valproate.

In this global, open-label extension study 523 participants received at least one dose of Lybalvi and 35.9% of participants completed the four-year treatment period. The safety profile of Lybalvi was consistent with previous studies. Patients' symptoms of schizophrenia or bipolar I disorder 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. Similarly, there were generally minimal changes in lipid and glycemic parameters, including HDL cholesterol, LDL cholesterol, triglycerides, fasting glucose and HbA1c over the measured time period. Overall, 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."

Alkermes expects to submit results from this open-label, long-term study to a peer-reviewed journal for publication and to present additional study results at upcoming scientific meetings.

Phase III, Open-Label Study Design: This was a multicenter, phase III, open-label extension study assessing the long-term safety, tolerability and durability of treatment effect of Lybalvi for up to four years. Patients were eligible to enroll within seven days of completing one of three antecedent phase III clinical trials investigating Lybalvi: the ENLIGHTEN-1 safety extension study; the ENLIGHTEN-2 safety extension study (rollover extensions of the ENLIGHTEN-1 and ENLIGHTEN-2 phase III pivotal randomized controlled trials in adults with schizophrenia); and the 12-week ENLIGHTEN-Early randomized controlled trial comparing Lybalvi to olanzapine in young adults with recent-onset schizophrenia, schizophreniform disorder, or bipolar I disorder.

In this long-term extension study, patients continued their daily dose of Lybalvi (olanzapine 5-20 mg + samidorphan 10 mg) from their antecedent study for up to an additional four years, with dose adjustments determined by the investigator. A total of 524 patients enrolled in the study, and 523 received ?1 dose of Lybalvi Baseline was established based on these 523 patients and changes as compared to baseline were based on those patients who completed four years of open-label treatment with Lybalvi. Patients were mostly male (61.6%) and White (72.7%), with a mean age of 35.1 years. Safety assessments included changes from baseline in body weight and waist circumference and the incidence of adverse events (AEs). Changes in lipid (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and total cholesterol and triglycerides) and glycemic (glucose and glycosylated hemoglobin [HbA1c]) parameters were evaluated. Antipsychotic efficacy was assessed using the Clinical Global Impressions–Severity (CGI-S) scale.