FDA Issues Complete Response for High-Dose Opioid Rescue Med

The FDA has issued a complete response letter for Orexo’s OX124. The product is a nasal rescue medication for opioid overdose containing a high dose of naloxone and is the first product based on Orexo’s drug delivery platform, amorphOX. AmorphOX is a powder-based technology that provides rapid absorption and high bioavailability of naloxone.

Drug overdose continues to be a major public health issue in the United States. From 2020 to 2021, opioid deaths rose 15%, according to CDC. More than 75% of the drug overdose deaths in 2021 involved an opioid.

The complete response letter indicates that regulators would like to see an additional human factors (HF) study and additional technical data on the final commercial product. The CRL does not indicate a need for additional clinical or non-clinical studies. N

A human factors study to assess how people use a device determine if there are any issues related to use. Regulators had previously requested this from Orexo, and company officials said in a news release that the study has been successfully completed. Orexo has worked to optimize the instructions of use.

Company officials said the requirement from FDA to provide additional technical data was unexpected, and they will work with the FDA to address this.

Nikolaj Sørensen

“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,” Nikolaj Sørensen, president and CEO, of Orexo, said in the release.

Orexo had submitted the application for OX124 in September 2023. The submission was supported by data from a pivotal study in healthy volunteers, where OX124 showed a significantly faster and higher absorption of naloxone compared with intramuscular dosing with an injection reference product.

In addition, development formulations of OX124 have in a previous exploratory clinical study in healthy volunteers demonstrated a more rapid absorption and higher bioavailability compared with the market leading naloxone rescue medication, even with the same dose as the comparator.