The FDA approved the antipsychotic combination of olanzapine plus samidorphan (Lybalvi) for adults with schizophrenia or bipolar I disorder, drugmaker Alkermes announced on Tuesday.
In schizophrenia, olanzapine-samidorphan is indicated as a monotherapy; in bipolar I disorder, the drug is approved as either a maintenance monotherapy or for the acute treatment of manic or mixed episodes as an adjunct to lithium or valproate.
The once-daily, oral treatment combines the atypical antipsychotic olanzapine (Zyprexa), which has been approved since 1996 as monotherapy. However, the major drawback with olanzapine alone is its association with substantial weight gain.
Offsetting this, the novel mu-opioid antagonist samidorphan, which has never been approved alone, was able to significantly reduce weight gain in patients while maintaining the efficacy of the antipsychotic.
Labeling for the drug will hold a warning on increased mortality in elderly patients with dementia-related psychosis and will be contraindicated for patients using opioids or currently undergoing opioid withdrawal.
Olanzapine-samidorphan will be formulated in fixed-dosage strengths composed of 10 mg for samidorphan, and 5 mg, 10 mg, 15 mg, and 20 mg for olanzapine.
The approval comes based on the ENLIGHTEN clinical program, which last fall swayed an FDA advisory committee to recommend the combination for approval, garnering a favorable vote of 11-6. While the panel was encouraged by the antipsychotic efficacy, some concerns still lingered over risks associated with the opioid antagonist component of the agent.
The phase III program found a significant reduction in Positive and Negative Syndrome Scale scores and improvement in the Clinical Global Impression-Severity scale when compared with placebo, along with far less weight gain than olanzapine alone.
“Samidorphan is believed to limit the pleasure of food intake that has been enhanced by olanzapine,” ENLIGHTEN-2 lead investigator Joseph McEvoy, MD, of Augusta University in Georgia and Duke University Medical Center in Durham, North Carolina, previously told MedPage Today. “Olanzapine is the most efficacious non-clozapine antipsychotic medication, and we want to be able to use it more, while managing its adverse effects. This study demonstrates a helpful mechanism to be able to do that.”
The announcement by Alkermes stated that it expects the new antipsychotic to be available in the U.S. in the fourth quarter of 2021.