In schizophrenia, "positive symptoms" refer to an excess or distortion of normal function (such as delusions, hallucinations and disorganized thinking) while "negative symptoms" refer to a reduction or absence of normal behaviors (blunted affect, reduction in quantity of words spoken, reduced goal-directed activity due to decreased motivation, emotional or social withdrawal and diminished ability to experience pleasure). Negative symptoms are often associated with reduced functioning in patients with schizophrenia and can be a predictor of poor treatment response; addressing them remains a treatment challenge in schizophrenia.1,2

"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, M.D. (MBChB), Chief Medical Officer and Executive Vice President, Research & Development at Alkermes. "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."

Data from the post hoc analysis were derived from 281 adults who completed ENLIGHTEN-1—a 4-week inpatient study evaluating the efficacy, safety and tolerability of LYBALVI compared to olanzapine and placebo in patients experiencing an acute exacerbation of schizophrenia—and who subsequently enrolled in a 52-week open-label extension study (ENLIGHTEN-1 Extension) in which all patients received LYBALVI. Patient 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 two subgroups: in patients with prominent negative symptoms* (n=186) at baseline and in patients 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 four 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.

  • Baseline scores: 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 patients 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.
  • Patients overall: Least squares (LS) mean changes from baseline in PANSS Negative Symptoms Subscale scores among all patients were −4.1 at week 4 and −7.6 at week 56. LS mean changes from baseline in Marder Negative Factor scores among all patients were −4.5 at week 4 and −8.2 at week 56.
  • Prominent subgroup: Among patients 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.
  • Predominant subgroup: A similar pattern of change was observed among patients 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.

According to study author Christoph U. Correll, M.D., Professor of Psychiatry at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, "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."