After CRL, Alkermes Wins FDA Approval for Schizophrenia Drug Lybalvi


Shares of Alkermes are climbing this morning after the company announced it finally won approval for its schizophrenia and bipolar I disorder drug, ALKS 3831 (olanzapine/samidorphan). 

The newly approved drug, dubbed Lybalvi, is a once-daily oral antipsychotic drug approved by the U.S. Food and Drug Administration (FDA) as both a maintenance monotherapy for these indications or for the acute treatment of manic or mixed episodes as a monotherapy or an adjunct to lithium or valproate.

Lybalvi is an atypical compound of Eli Lilly’s Zyprexa, an established antipsychotic agent, and samidorphan, an opioid antagonist that is a new chemical entity. Samidorphan was included in the makeup of the medication to control weight gain and other side effects that have been commonly established to the Eli Lilly drug. Weight gain is a concern for patients taking second-generation antipsychotics like Zyprexa due to its relationship to metabolic syndrome.

Richard Pops, chairman and chief executive officer of Alkermes, said Lybalvi represents an important new treatment option for adults with schizophrenia or bipolar I disorder, both of which are complex and difficult-to-treat brain disorders. 

Lybalvi was approved based on data from the ENLIGHTEN clinical development program. The ENLIGHTEN-1 study evaluated the antipsychotic efficacy of Lybalvicompared to placebo over four weeks, and the ENLIGHTEN-2 study assessed weight gain with ALKS 3831 compared to olanzapine over six months. 

The Phase III ENLIGHTEN-2 study met its primary endpoints of a lower mean percent weight gain from baseline at six months than those receiving olanzapine and a lower proportion of patients who gained 10% or more of their baseline body weight at six months compared to the cohort receiving olanzapine.

Approval for Lybalvi faced a tough road. In December, the FDA issued a Complete Response Letter to Alkermes over the coating process of the tablets manufactured at Alkermes’ facility in Wilmington, Ohio. There were no clinical issues associated with the CRL. Alkermes resubmitted its New Drug Application in late December after addressing the manufacturing issues raised by the FDA. 

Just two months prior to the CRL, the schizophrenia drug was overwhelmingly supported by an FDA advisory committee. In October 2020, a joint meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 16-1 in favor of the efficacy of ALKS 3831. It also received strong support for its safety profile during that meeting. There had been some concern about Lybalvi heading into that meeting. FDA staff members raised concerns over the potential for abuse due to the fact that the drug’s makeup includes an opioid antagonist.


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