Alkermes plc (Nasdaq: ALKS) today announced that the U.S. Food and Drug Administration (FDA) has approved Lybalvi (olanzapine and samidorphan) 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. Lybalvi is a once-daily, oral atypical antipsychotic composed of olanzapine, an established antipsychotic agent, and samidorphan, a new chemical entity.

"Schizophrenia and bipolar I disorder are complex, chronic diseases and there remains a persistent need for new medications with proven efficacy and safety. Olanzapine, a highly-efficacious atypical antipsychotic, is associated with significant side effects, including weight gain, that may impact patients' treatment experiences and limit its use," said René S. Kahn, M.D., Ph.D., Esther and Joseph Klingenstein Professor & Chair, Department of Psychiatry and Behavioral Health System at the Icahn School of Medicine at Mount Sinai. "With the efficacy of olanzapine and evidence of less weight gain in patients with schizophrenia, Lybalvi brings a welcome new addition to our medication arsenal."

"Lybalvi represents an important new treatment option for adults with schizophrenia or bipolar I disorder, their clinicians and caregivers, and reflects Alkermes' commitment to developing new therapies that support patient-centered care," said Richard Pops, Chairman and Chief Executive Officer at Alkermes. "We share this accomplishment with our employees and the many researchers, advocates, clinicians and patients who have been essential to the Lybalvi development program since its inception. Our existing commercial capabilities and presence in the antipsychotic market with ARISTADA? provide an important foundation for the commercialization of Lybalvi, and we look forward to making this new medicine available to patients and clinicians later this year."

In the ENLIGHTEN clinical development program, Lybalvi demonstrated antipsychotic efficacy, safety and tolerability, including statistically significantly less weight gain than olanzapine in patients with schizophrenia in the ENLIGHTEN-2 study. Results from the ENLIGHTEN program's pivotal ENLIGHTEN-1 efficacy study and ENLIGHTEN-2 weight study have been published in peer-reviewed journals and are included in the approved labeling for Lybalvi. The FDA approved LYBALVI under the 505(b)(2) regulatory pathway based on data from 27 clinical studies, including 18 studies evaluating Lybalvi and nine studies evaluating samidorphan alone, and the FDA's findings of safety and effectiveness of olanzapine in the treatment of bipolar I disorder and schizophrenia. Data suggest that olanzapine-associated weight gain is disease independent.

"People living with schizophrenia or bipolar I disorder must evaluate both efficacy and tolerability when making treatment decisions," said Paul Gionfriddo, President and CEO of Mental Health America (MHA). "We are grateful that companies like Alkermes are driven to continue developing new treatment options in psychiatry that seek to address unmet needs of our community and we applaud the FDA for considering the experiences of individuals living with these conditions."  

Alkermes expects to make Lybalvi available for patients in the fourth quarter of 2021. 

About Schizophrenia 

Schizophrenia is a serious brain disorder marked by positive symptoms (hallucinations and delusions, disorganized speech and thoughts, and agitated or repeated movements) and negative symptoms (depression, blunted emotions and social withdrawal).4 Schizophrenia affects approximately 1.1% of the U.S. population.5 

About Bipolar I Disorder

Bipolar disorder is a brain disorder that is marked by extreme changes in a person's mood, energy and ability to function. Individuals with this brain disorder may experience debilitating changes in mood from extreme highs (mania) to extreme lows (depression). Bipolar I disorder is characterized by the occurrence of at least one manic episode, with or without the occurrence of a major depressive episode, and affects approximately one percent of the adult population in the United States in any given year.6

About the ENLIGHTEN Clinical Development Program

The ENLIGHTEN clinical development program for Lybalvi includes two key studies in patients with schizophrenia: ENLIGHTEN-1 and ENLIGHTEN-2.

ENLIGHTEN-1 evaluated the antipsychotic efficacy, safety and tolerability of Lybalvi compared to placebo over four weeks in 403 patients experiencing an acute exacerbation of schizophrenia. This study met its prespecified primary endpoint, with Lybalvi demonstrating statistically significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) scores compared to placebo (p<0.001). An olanzapine comparator arm was also included, which achieved similar improvements from baseline PANSS scores compared to placebo (p=0.004). The most common adverse events (AEs) for both the Lybalvi and olanzapine treatment groups were weight gain, somnolence and dry mouth.

ENLIGHTEN-2 evaluated the weight gain profile of Lybalvi compared to olanzapine over six months in 561 patients with stable schizophrenia. This study met its prespecified co-primary endpoints, demonstrating both a lower mean percent weight gain from baseline at six months compared to the olanzapine group (p=0.003) and a lower proportion of patients who gained 10% or more of their baseline body weight at six months compared to the olanzapine group (p=0.003). The most common AEs reported in the Lybalvi treatment group were weight gain, somnolence and dry mouth; the most common AEs reported in the olanzapine treatment group were weight gain, somnolence and increased appetite. 

The program also included supportive studies to evaluate the pharmacokinetic and metabolic profile and long-term safety of Lybalvi, and pharmacokinetic bridging studies comparing LYBALVI and ZYPREXA? (olanzapine).

About Lybalvi (olanzapine and samidorphan)

Lybalvi (olanzapine and samidorphan) is a once-daily, oral atypical antipsychotic drug 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. Lybalvi is composed of olanzapine, an established antipsychotic agent, co-formulated with samidorphan, a new chemical entity, in a single bilayer tablet. Lybalvi will be available in fixed dosage strengths composed of 10 mg of samidorphan and 5 mg, 10 mg, 15 mg or 20 mg of olanzapine.