Alkermes Announces Positive Topline Results From ENLIGHTEN-Early Phase 3b Study of LYBALVI® in Patients Early in Illness

- LYBALVI Demonstrated Less Weight Gain Compared to Olanzapine in Patients With Schizophrenia, Schizophreniform Disorder or Bipolar I Disorder -

DUBLIN, Feb. 8, 2022 /PRNewswire/ -- Alkermes plc (Nasdaq: ALKS) today announced positive topline results from ENLIGHTEN-Early, a phase 3b study that evaluated the effect of LYBALVI® (olanzapine and samidorphan) compared to olanzapine on body weight in young adult patients (ages 16 to 39; mean age: 26 years) with schizophrenia, schizophreniform disorder or bipolar I disorder who were early in their illness. The study met its pre-specified primary endpoint, as patients treated with LYBALVI experienced statistically significantly less weight gain than patients treated with olanzapine at Week 12 (mean percent change from baseline body weight: 6.77% for olanzapine vs. 4.91% for LYBALVI, p=0.012). Consistent with the ENLIGHTEN-2 pivotal study,1 a numerical difference in average weight gain between treatment arms was observed early in treatment and continued to separate through the study's prespecified primary endpoint. LYBALVI is approved for the treatment of adults with schizophrenia, and for the treatment of adults with bipolar I disorder, as a maintenance monotherapy or for the acute treatment of manic or mixed episodes as monotherapy or 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. 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," said Craig Hopkinson, M.D., Executive Vice President of Research & Development and Chief Medical Officer at Alkermes.

"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, M.D., Professor of Psychiatry and Molecular Medicine at Hofstra Northwell School of Medicine. "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.2"

The study employed a hierarchical testing methodology for four pre-specified secondary endpoints. 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. A numerical difference was observed between treatment arms across all secondary endpoints in favor of LYBALVI. Results of the secondary endpoints were as follows:

• The proportion of patients who gained 10% or more of their baseline body weight at three months was 30.4% for olanzapine vs. 21.9% for LYBALVI (p=0.075).
• The proportion of patients who gained 7% or more of their baseline body weight at three months was 44.8% for olanzapine vs. 33.1% for LYBALVI.
• The mean change from baseline in waist circumference at three months was 3.90 cm for patients treated with olanzapine vs. 2.99 cm for patients treated with LYBALVI.
• Treatment with LYBALVI was associated with improvements in symptoms of schizophrenia and bipolar I disorder over three months, as measured by the Clinical Global Impression of Severity (CGI-S) scale (mean change from baseline in CGI-S score of -0.82).

The safety profile of LYBALVI was consistent with previous studies. Overall, 63.5% of patients receiving LYBALVI and 63.3% of patients receiving olanzapine reported adverse events while on treatment. The most common adverse events reported for the LYBALVI treatment group were weight gain, somnolence and increased alanine aminotransferase and for the olanzapine treatment group were weight gain, somnolence and increased waist circumference. Serious adverse events occurred in 3.8% of LYBALVI patients and 3.7% of olanzapine patients during the treatment period. A majority of patients in both treatment groups completed the three-month study (78.2% of patients who received LYBALVI and 74.9% of patients who received olanzapine).

Alkermes expects to submit results from the ENLIGHTEN-Early study to a peer-reviewed journal for publication and present additional study results at upcoming scientific meetings.

ENLIGHTEN-Early Study DesignENLIGHTEN-Early was a multicenter, randomized, double-blind, phase 3 study that evaluated the effect of LYBALVI compared to olanzapine on body weight over three months in young adults with schizophrenia, schizophreniform disorder or bipolar I disorder who were early in their illness. To qualify for participation as a patient "early in illness", subjects had to have less than 24 weeks of previous treatment with antipsychotics and less than four years elapse since the initial onset of active symptoms. A total of 428 patients (aged ≥16 and