The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Adamis Pharmaceuticals regarding the New Drug Application (NDA) for Zimhi™, an investigational high-dose naloxone injection product for the treatment of opioid overdose.

In the CRL, the FDA stated that the NDA could not be approved in its present form due to new issues pertaining to Chemistry, Manufacturing and Controls. This is the second time the Company has received a CRL related to the Zimhi application, although neither letter was related to clinical safety or efficacy. 

To address these issues, the Company plans to provide the FDA with additional analysis and information stated in the letter. “This is a very disappointing setback that was totally unexpected since we completed the extractables and leechables issues that were associated with the first CRL,” said Dr Dennis J. Carlo, President and CEO of Adamis. “We believe the comments and recommendations stated in the CRL can be addressed and overcome. […] As soon as reasonably possible, we will resubmit additional information and analysis of data to the FDA for the NDA.”

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Naloxone, an opioid antagonist, is used for the emergency treatment of known or suspected opioid overdose. Currently, naloxone is supplied in ampules and vials for IV, IM or SC administration, in a prefilled auto-injector, and as a nasal spray. According to case reports, higher doses of naloxone may be needed to reverse opioid overdoses resulting from carfentanil ingestion.

In July 2020, the FDA recommended that health care professionals discuss naloxone with all patients when prescribing opioid medications. The Agency also announced that drug manufacturers of opioid medications would need to add naloxone recommendations to the prescribing information.

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Adamis Pharmaceuticals receives a Complete Response Letter from the FDA regarding Zimhi. [press release]. San Diego, CA: Adamis Pharmaceuticals; November 16, 2020.