FDA Approves Olanzapine and Samidorphan for Schizophrenia, Bipolar I Disorder

The US Food and Drug Administration (FDA) has approved olanzapine and samidorphan (LYBALVI) as monotherapy for adults with schizophrenia and bipolar I disorder. The once-daily, oral atypical antipsychotic has also been approved as monotherapy or adjunctive to lithium or valproate for the acute treatment of manic or mixed episodes.

"Schizophrenia and bipolar I disorder are complex, chronic diseases and there remains a persistent need for new medications with proven efficacy and safety. Olanzapine, a highly-efficacious atypical antipsychotic, is associated with significant side effects, including weight gain, that may impact patients' treatment experiences and limit its use," said René S. Kahn, M.D., Ph.D. of the Department of Psychiatry and Behavioral Health System at the Icahn School of Medicine at Mount Sinai, in a statement.

"With the efficacy of olanzapine and evidence of less weight gain in patients with schizophrenia, LYBALVI brings a welcome new addition to our medication arsenal,” he continued.

Supporting Data

FDA approval was based on findings from 27 clinical studies—some of which assessed olanzapine and samidorphan together or each agent alone. Overall, olanzapine and samidorphan demonstrated high antipsychotic efficacy, safety, and tolerability.

The medication was also associated with statistically significantly less weight gain than patients on olanzapine alone.

ENLIGHTEN-1 and ENLIGHTEN-2, 2 key trials, evaluated the drug in 403 patients with schizophrenia. ENLIGHTEN-1 met its primary endpoint, showing significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) scores compared to placebo (P<0.001).

ENLIGHTEN-2 also met its co-primary endpoints. Olanzapine and samidorphan was linked to a lower percent weight gain from baseline at 6 months compared to the olanzapine group (P = 0.003) as well as lower proportion of patients who gained 10% or more of their baseline body weight at 6 months compared to an olanzapine-only arm (P=0.003).

“We share this accomplishment with our employees and the many researchers, advocates, clinicians and patients who have been essential to the LYBALVI development program since its inception,” said Richard Pops, Chairman and Chief Executive Officer at Alkermes, in a statement. “Our existing commercial capabilities and presence in the antipsychotic market with ARISTADA® provide an important foundation for the commercialization of LYBALVI, and we look forward to making this new medicine available to patients and clinicians later this year."

Last year, the FDA issued a Complete Response Letter (CRL) to Alkermes for olanzpaine and samidorphan, formerly ALKS 3831, due to conditions related to the tablet coating process at an Ohio facility. Since then, Alkermes has worked closely with the FDA to resolved such discrepances.