An investigational antipsychotic medication combining olanzapine and samidorphan (OLZ/SAM) mitigates weight gain across different subgroups of patients with schizophrenia known to be at risk for weight gain with olanzapine therapy, according to new data from the ENLIGHTEN-2 study. Olanzapine is an effective antipsychotic, but is associated with weight gain and waist-circumference increases. "People living with severe mental illness, schizophrenia and bipolar, shouldn't have to make a trade-off between a drug that may give them good efficacy and weight gain," Dr. Adam Simmons with Alkermes, Inc, noted in a phone interview with Reuters Health. Alkermes is developing OLZ/SAM, a once-daily, oral therapy, and funded the study. Samidorphan is a mu-opioid receptor antagonist. ENLIGHTEN-2 was a 24-week phase-3, multicenter, double-blind study evaluating weight gain in 561 outpatients with schizophrenia treated with OLZ/SAM or olanzapine by random allocation. The overall results showed that treatment with OLZ/SAM significantly mitigated weight gain versus olanzapine over 24 weeks, without compromising antipsychotic efficacy. At the Schizophrenia International Research Society (SIRS) virtual annual meeting, Dr. Simmons reported prespecified subgroup analyses for 266 patients treated with OLZ/SAM and 272 treated with olanzapine, focusing on the impact of sex, age (age <30 years vs. 30 and older), race (Black and non-Black) and BMI (< 27/kg/m2 vs. 27 kg/m2 or higher). In the overall group, 17.8% of patients on the combination drug saw a weight gain of at least 10% by 24 weeks versus 29.8% of those on olanzapine alone, a significant difference. Mirroring the main study findings, in all subgroups, treatment with OLZ/SAM led to less weight gain versus olanzapine, based on percent change in weight from baseline and on the proportion of patients with 10% or greater weight gain at 24 weeks across patient subgroups, Dr. Simmons reported. "The weight effect that we see in the general population, we see across all high-risk subgroups; that is we see that same mitigation of weight gain with olanzapine/samidorphan versus olanzapine," Dr. Simmons told Reuters Health. In a companion presentation at SIRS, researchers reported post-hoc analyses of ENLIGHTEN-2 assessing the effects of OLZ/SAM (versus olanzapine) across multiple cardiometabolic risk factors. Overall, patients treated OLZ/SAM were less likely to experience increases in blood pressure or BMI, or to develop metabolic syndrome, than those treated with olanzapine alone, Dr. Simmons told Reuters Health. Alkermes Inc has submitted a new-drug application for OLZ/SAM (Lybalvi) to the U.S. Food and Drug Administration and expects a decision June 1. Several authors have disclosed financial relationships with the company. —Megan Brooks Source
