Lybalvi Associated With Improvement in Negative Symptoms of Schizophrenia: Findings From Long-Term Analysis

Alkermes today announced the publication of a 56-week post hoc analysis of the effects of olanzapine and samidorphan (Lybalvi) on negative symptoms in adults living with schizophrenia, which found that treatment with Lybalvi was associated with significant and durable improvement in mean negative symptom scores.^1,2 Lybalvi is currently approved in the US for the treatment of schizophrenia in adults, for the treatment of bipolar I disorder in adults, as a maintenance monotherapy or for the acute treatment of manic or mixed episodes, and as monotherapy or as adjunct to lithium or valproate.³

“Publication of this negative symptom post hoc analysis adds to a growing body of evidence supporting the role of Lybalvi in treating the complex symptomology related to schizophrenia,” said Craig Hopkinson, MD, MBChB, the chief medical officer and executive vice president of research & development at Alkermes.

Data from the post hoc analysis were derived from 281 adult participants who completed ENLIGHTEN-1—which was a 4-week inpatient study evaluating the efficacy, safety, and tolerability of Lybalvi compared with olanzapine and placebo in participants experiencing an acute exacerbation of schizophrenia—and who subsequently enrolled in a 52-week open-label extension study (ENLIGHTEN-1 Extension), in which all participants received Lybalvi. Participant symptoms were assessed using the 30-item Positive and Negative Syndrome Scale (PANSS). This analysis looked at several subscales of the PANSS, including Negative Symptoms, Positive Symptoms, and General Psychopathology Subscale scores and the Marder Negative Factor scores; Lybalvi demonstrated improvements from baseline in all subscale scores. In addition, the analysis looked at changes in 2 subgroups: in participants with prominent negative symptoms (n=186) at baseline and in participants with predominant negative symptoms/low positive symptoms (n=48) at baseline, in order to ascertain if the changes in negative symptoms were driven by changes in positive symptoms.

The analysis showed decreased negative symptoms over the first 4 weeks in a pooled analysis of treatment arms (Lybalvi, olanzapine and placebo) in ENLIGHTEN-1 with continued improvement over the 52 weeks of open-label treatment with Lybalvi. The mean PANSS Negative Symptoms Subscale score at baseline was 25.7 and the mean Marder Negative Factor score at baseline was 25.2 in participants overall. The mean Marder Negative Factor score at baseline was 27.7 in the prominent negative symptoms subgroup and 28.2 in the predominant negative symptoms subgroup. Least squares (LS) mean changes from baseline in PANSS Negative Symptoms Subscale scores among all participants were −4.1 at week 4 and −7.6 at week 56. LS mean changes from baseline in Marder Negative Factor scores among all participants were −4.5 at week 4 and −8.2 at week 56. Among participants with prominent negative symptoms at baseline, LS mean changes from baseline in PANSS Negative Symptoms Subscale scores were −4.6 at week 4 and −8.7 at week 56, and LS mean changes in Marder Negative Factor scores were −5.0 at week 4 and −9.6 at week 56. A similar pattern of change was observed among participants with predominant negative symptoms at baseline: LS mean changes from baseline in Marder Negative Factor scores across patients in this subgroup were −4.7 at week 4 and −8.9 at week 56.

“Lybalvi has already been shown to provide the established efficacy of olanzapine as measured by PANSS total scores while mitigating olanzapine-associated weight gain and its effects on positive symptoms of schizophrenia have been evaluated. This post hoc analysis of the effect of Lybalvi on negative symptoms, which remain a persistent treatment challenge, further validates Lybalvi’s utility for the treatment of schizophrenia, a condition characterized by complex symptom domains,” said study author Christoph U. Correll, MD, a professor of psychiatry at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell.

The analysis, “The Efficacy of Olanzapine/Samidorphan on Negative Symptoms: A Post Hoc Analysis of 56-Week Treatment in Patients With Schizophrenia,” was published in the peer-reviewed publication The Journal of Clinical Psychiatry.

“Alkermes remains committed to expanding the field’s understanding of this challenging disease and the impact of medicine in helping patients manage their illness. We look forward to continued engagement with the scientific community in this important discourse,” concluded Hopkinson.

References

1. McIntyre RS, Matthews DM, Arevalo C, et al. The efficacy of olanzapine/samidorphan on negative symptoms: a post hoc analysis of 56-week treatment in patients with schizophrenia. J Clin Psychiatry. 2026;87(2):25m16170.

2. Findings from long-term analysis of the effects of Lybalvi® (olanzapine and samidorphan) on negative symptoms of schizophrenia published in The Journal of Clinical Psychiatry. News release. April 14, 2026. Accessed April 14, 2026. https://investor.alkermes.com/news-releases/news-release-details/findings-long-term-analysis-effects-lybalvir-olanzapine-and

3. Alkermes announces FDA approval of Lybalvi™ for the treatment of schizophrenia and bipolar I disorder. News release. June 1, 2021. Accessed April 14, 2026. https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-fda-approval-lybalvitm-treatment/