FDA Issues Complete Response Letter for Olanzapine/Samidorphan

While the CRL did not raise clinical concerns, the Agency noted that certain conditions related to the tablet coating process needed to be resolved.

The Food and Drug Administration (FDA) has issued a complete response letter (CRL) to Alkermes regarding the New Drug Application (NDA) for olanzapine/samidorphan (ALKS 3831) for the treatment of adults with schizophrenia and bipolar I disorder.

While the CRL did not raise any clinical concerns, the Agency requested that certain conditions related to the tablet coating process at the Company’s facility would need to be resolved prior to a decision being made on the application.

“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,” said Craig Hopkinson, MD, Chief Medical Officer and Executive Vice President of Research & Development at Alkermes. “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.”

ALKS 3831 is comprised of samidorphan, a mu-opioid receptor antagonist, co-formulated with the established antipsychotic agent olanzapine, in a single bilayer tablet. The once-daily oral formulation is designed to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The NDA was supported by data from the ENLIGHTEN clinical program, which includes two phase 3 studies.

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Recently, the FDA’s Psychopharmacologic Drug Advisory Committee and the Drug Safety and Risk Management Advisory Committee jointly voted in favor of the approval of the treatment, although a concern related to the opioid antagonist effect of samidorphan in real-world settings was raised during the meeting.  When asked whether labeling was sufficient to mitigate the risks, the panel voted 11 yes and 6 no.

For more information visit alkermes.com.


Alkermes receives FDA complete response letter related to ALKS 3831 manufacturing records review. [press release]. Dublin, Ireland; November 17, 2020.