FDA Issues CRL For ALKS 3831

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for ALKS 3831, a combination treatment involving olanzapine and samidorphan for adults with schizophrenia and adults with bipolar I disorder.

The CRL, sent to developer Alkermes plc, does not include any clinical efficacy or safety issues. However, following a remote review of manufacturing recorders, the FDA found certain conditions related to the tablet coating process at a facility in Ohio need to be addressed before approving the New Drug Application (NDA).

The NDA was submitted based on the data from 27 clinical trials, including 18 studies evaluating ALKS 3831 and 9 trials evaluating samidorphan alone. The study drug has demonstrated a consistent antipsychotic efficacy, safety, and tolerability profile in patients with schizophrenia throughout the clinical development program.

The FDA found certain development batches of the drug have issues, but Alkermes has stated that the issues have since been resolved and sufficient data is available to address what is raised in the CRL.

Because of the ongoing coronavirus disease 2019 (COVID-19) pandemic, the FDA did not conduct an on-site Pre-Approval Inspection (PAI) of the Wilmington, OH manufacturing facility. However, they did conduct a remote review of records.

The company has stated plans to submit data and work closely with the FDA to resolve any remaining discrepancies.

"We will continue to work closely with the Agency in an expeditious manner to support approval of ALKS 3831 for the treatment of schizophrenia and bipolar I disorder and believe we have a clear path to resolution,” Craig Hopkinson, MD, Chief Medical Officer and Executive Vice President of Research & Development at Alkermes, said in a statement. “Importantly, there were no clinical issues identified in the CRL pertaining to ALKS 3831's efficacy or safety, and no new studies were requested for approval of the application.”

In October, the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 16-1 that the samidorphan meaningfully mitigates olanzapine-associated weight gain.

The committee also ruled the safety profile of ALKS 3831, developed by Alkermes, has been adequately characterized with a 13-3 vote.

Finally, the committees jointly voted that labeling is sufficient to mitigate the risks related to the opioid antagonist action of samidorphan in a 11-6 vote.