Alkermes Overcomes Regulatory Setbacks to Snag FDA Approval for Schizophrenia Drug

After experiencing several regulatory setbacks in the past three years, Alkermes must be finally breathing a sigh of relief. The Waltham, MA-based company announced the FDA approval of Lybalvi (olanzapine and samidorphan), it’s oral antipsychotic for treating adults with schizophrenia and bipolar I disorder.

“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 CEO at Alkermes.

A Regulatory Success to Savor

In November 2020, the FDA turned down Lybalvi’s (then ALKS 3831) application with a complete response letter (CRL) citing issues with the tablet coating process at the Wilmington, Ohio facility. That rejection could have felt like a déjà vu moment for Alkermes. Two years earlier, the company had endured a harsh advisory panel review that voted 21-2 against the approval of its experimental depression drug, ALKS 5461, which eventually led to rejection and sinking stocks.

The CRL for ALKS 3831 would have hurt more because it received a relatively favorable vote from the FDA panel. Alkermes though swiftly resolved those manufacturing issues and bounced back to resubmit the application. Six months later, Lybalvi has finally garnered the FDA’s nod as Alkermes’ first oral antipsychotic.

Confronting the Schizophrenia Challenge

Schizophrenia is a chronic disorder affecting close to 20 million people worldwide. The illness results from complex crosstalk between genetic and environmental factors and is typically treated using antipsychotics. Although affordable, first-generation antipsychotics could cause serious neurological adverse effects.

But second-generation antipsychotics, also known as atypical antipsychotics pose a lower risk of side effects. Among them, Eli Lilly’s Zyprexa Relprevv (olanzapine) has grown into a very popular treatment, despite its tendency to cause significant weight gains in patients. Approved in 2009, the drug yielded Lilly a revenue of $406.6 million in 2020.

Alkermes’ Lybalvi, on the other hand, is designed to negate the weight gain side effect of olanzapine by co-formulating it with samidorphan, a new chemical entity. Lybalvi met the primary endpoints in two of the key Phase 3, ENLIGHTEN trials.

In the ENLIGHTEN-2 trial, Lybalvi demonstrated 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).

“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,” said René S. Kahn, M.D., Ph.D., Professor & Chair, Department of Psychiatry and Behavioral Health System, Icahn School of Medicine at Mount Sinai.

Author

Rajaneesh K. Gopinath