Olanzapine, Samidorphan Effective for Long-Term Schizophrenia, Bipolar Disorder Treatment

New data from a phase 3, open-label extension study are providing insight into the long-term safety, tolerability, and durability of olanzapine and samidorphan (LYBALVI) in adults with schizophrenia, schizophreniform disorder, and bipolar I disorder.

Announced by Alkermes plc on January 03, 2024, topline results of the long-term safety study suggest use of the agent, which is already approved by the US Food and Drug Adminsitatration for the treatment of schizophrenia and adults with bipolar I disorder, was generally well-tolerated with stability of body weight and metabolic profile as well as durable symptom control for up to 4 years of treatment.^1,2

“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 investigator Jacob S. Ballon, MD, MPH, clinical professor of Psychiatry and Behavioral Sciences at Stanford University.¹ “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.”

A disorder characterized by symptoms of hallucinations, delusions, disorganized speech and thoughts, agitated or repeated movements, depression, blunted emotions, and social withdrawal, recent data indicates schizophrenia affects 1.1% of the US population while bipolar I disorder affects 1% of the US population.^1,2

For inclusion in the long-term safety study, participants were required to have been enrolled in 1 of the 3 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

A total of 523 participants received ≥ 1 dose of LYBALVI, consisting of 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.¹

In total, 35.9% of participants completed the 4-year treatment. Topline results indicates symptoms of schizophrenia or bipolar I disorder, which were measured using Clinical Global Impression of Severity, remained stable with up to 4 years of treatment (mean change from baseline in CGI-S score of -0.28). The announcement from Alkermes suggested long-term treatment 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 4 years of treatment. Additionally, the company stated 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.¹

According to Alkermes plc, olanzapine and samidorphan had a consistent safety profile from the previous studies. In the study, 60% of patients reported an adverse event, with most adverse events mild to moderate in severity. The most common events were weight gain, headache, anxiety, insomnia, somnolence, nausea, and weight decrease.¹

In their announcement, Alkermes warned against use of among elderly patients with dementia-related psychosis treatment. Alkermes also advised individuals taking short-acting opioids to have a 7-day opioid-free interval from the last use prior to initiating therapy and a 14-day opioid-free interval from the last use for those using long-acting opioids.¹

Alkermes expects to submit results from the open-label, long-term study to a peer-reviewed journal for publication and to present further data from the study at upcoming scientific meetings.¹

"In this study, patients taking LYBALVI experienced sustained treatment effect and tolerability, including stability across multiple metabolic parameters,” said Craig Hopkinson, MD, executive vice president of research and development and chief medical officer at Alkermes.¹ “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.”

^References

1. ^{Alkermes Announces Topline Results from Long-Term, Open-Label Safety and Durability of Treatment Effect Study of LYBALVI® (olanzapine and samidorphan). PR Newswire. January 3, 2024. https://www.prnewswire.com/news-releases/alkermes-announces-topline-results-from-long-term-open-label-safety-and-durability-of-treatment-effect-study-of-lybalvi-olanzapine-and-samidorphan-302024987.html. Accessed January 5, 2024.}
2. ^{Alicea, J. FDA Approves Olanzapine and Samidorphan for Schizophrenia, Bipolar I Disorder. HCPLive. June 1, 2021. https://www.hcplive.com/view/fda-approves-olanzapine-samidorphan-schizophrenia-bipolar-disorder. Accessed January 5, 2024.}