FDA Declines Approval of High-Dose Naloxone Rescue Medication, OX124 for a Second Time

The US Food and Drug Administration (FDA) declined to approve OX124, a high-dose naloxone rescue medication that is currently in development for opioid overdose, the manufacturer, Orexo, said in a July 16, 2024, announcement. It is the second rejection of the product in the past 15 months.

According to Orexo, the FDA issued a complete response letter (CRL) for the new drug application (NDA) that was submitted for OX124 in September 2023. In the CRL, the agency stated a need for an additional Human Factors (HF) study and more technical data on the final commercial product. The CRL does not indicate a need for additional clinical or nonclinical studies.

The FDA’s request for an additional HF study is “in line with previous communication” with the agency, Orexo stated, adding that it has already completed such a study to help determine if there are any issues related to use.

Orexo added that the FDA’s request for additional technical data was unexpected and that the company will work with the agency to enable a resubmission of the drug’s NDA.

The company states it had already generated the requested technical data from its pilot scale manufacturing and is confident the information supports approval of OX124. The FDA, however, has requested data from the established “commercial scale manufacturing.”

“I am impressed by the vigour and agility of the teams in Sweden and the US in addressing FDA’s concerns from April regarding the instructions for use and our ability to complete a new human factors study shortly. However, I am surprised with the agency´s other requests with regards to additional technical data from final commercial product, but I am confident we can address this efficiently,” Nikolaj Sørensen, president and CEO of Orexo, said in the announcement. “We remain confident our powerful life-saving medication, OX124, can contribute to reducing the steep number of Americans who die from overdoses caused by the increasingly prevalent synthetic opioids.”

After resubmission of the NDA, the new review will require up to 6 months.

Reference: Orexo shares new information on OX124, a high-dose naloxone rescue medication in development for opioid overdose. News release. July 17, 2024. Accessed July 17, 2024. https://orexo.com/posts/2024-07-16-orexo-shares-new-information-on-ox124-a-high-dose-naloxone-rescue-medication-in-development-for-opioid-overdose