The treatment met the pre-specified primary endpoint of significantly less weight gain in the ENLIGHTEN-Early trial.
Topline results from the ongoing ENLIGHTEN-Early study show olanzapine and samidorphan (LYBALVI) has a positive impact on body weight in young adult patients with schizophrenia compared to olanzapine.
Alkermes plc announced the results on Feb. 8 for the phase 3b study in 428 patients aged 16-39 years with schizophrenia, schizophreniform disorder, or bipolar I disorder who were early in their illness.
The investigators found the drug met the pre-specified primary endpoint of statistically significant less weight gain compared to patients treated with just olanzapine at week 12. The mean percent change from baseline body weight was 6.77% for olanzapine compared to 4.91% for the olanzapine and samidorphan group (P = 0.012).
For the 4 prespecified secondary endpoints, the investigators implemented a hierarchical testing methodology.
Doing this, they found the first secondary endpoint did not achieve the pre-specified significance level, which precluded the assessment of statistical significance of the subsequent endpoints in the hierarchy.
There was also a numerical difference observed between treatment arms across all secondary endpoints in favor of the olanzapine and samidorphan treatment.
For secondary endpoints, 30.4% of the olanzapine group gained 10% or more of their baseline body weight after 3 months, compared to 21.9% of the olanzapine and samidorphan group (P = 0.075).
In addition, the proportion of patients who gained 7% or more of their baseline body weight at 3 months was higher in the olanzapine group (44.8%) than it was in the study drug arm (33.1%).
The mean change from baseline in waist circumference was 3.90 cm in the olanzapine group at 3 months, compared to 2.99 cm in the combination drug group.
Finally, treatment was linked to improvements in schizophrenia symptoms and bipolar I disorder symptoms over 3 months, measured by the Clinical Global Impression of Severity (CGI-S) scale (mean change from baseline in CGI-S score of -0.82).
For safety, 63.5% of the olanzapine and samidorphan group reported adverse events, compared to 63.3% of the olanzapine group.
The most common adverse event in the target group was weight gain, somnolence, and increased alanine aminotransferase.
There were also comparable serious adverse events found in both groups, with 3.7% of olanzapine patients and 3.8% of the olanzapine and samidorphan patients reporting.
"Olanzapine is well-known as an efficacious medicine but is often not used as a first-line treatment for early-in-illness patients due, in part, to concerns about weight gain," said Christoph Correll, MD, Professor of Psychiatry and Molecular Medicine at Hofstra Northwell School of Medicine, in a statement. "We're encouraged to see the positive results of this study in patients who have had less exposure to antipsychotic therapy and may be particularly susceptible to olanzapine-induced weight gain."
The results were consistent with the ENLIGHTEN-2 pivotal study, in which investigators found a numerical difference in average weight gain between the 2 treatment groups early in treatment. This continued to separate through the study’s prespecified primary endpoint.
Olanzapine and samidorphan is currently approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with schizophrenia and adult patients with bipolar I disorder as a maintenance monotherapy.
The treatment is also approved as an acute treatment of manic or mixed episodes as a monotherapy or as an adjunct to lithium or valproate.
“We're pleased to share topline results from the ENLIGHTEN-Early study, in which LYBALVI demonstrated less mean weight gain compared to olanzapine in patients early in illness with schizophrenia, schizophreniform disorder or bipolar I disorder,” Craig Hopkinson, MD, Executive Vice President of Research & Development and Chief Medical Officer at Alkermes, said in a statement. “These results complement the weight gain profile of LYBALVI shown in the ENLIGHTEN-2 pivotal study and reinforce the potential of LYBALVI as a new treatment option for adults living with schizophrenia or bipolar I disorder.”