FDA gives another thumbs down to Orexo's nasal spray for opioid overdose

For the second time in 15 months, the FDA has rejected Orexo’s OX124 (naloxone), a nasal spray rescue treatment for opioid overdoses.

In a complete response letter (CRL), the United States regulator identified two issues with the application, including one which was “unexpected,” the Swedish drug delivery specialist said in its release.

The FDA wants to see “additional technical data on the final commercial product.” In the application, according to Orexo, data were generated from “pilot scale manufacturing” and support approval. But the agency disagrees and is requesting data from “commercial scale manufacturing,” the company added.

Orexo CEO Nikolaj Sørensen said in the release that he was “surprised” by the technical data request but “confident we can address this efficiently.”

Additionally, while the FDA is not requesting that Orexo conducts another trial, it does need to see the results of another “human factor” study showing that patients can use the product correctly. Orexo has already completed this study, it said, after the agency cited the shortfall in a discussion with the company in April.

Orexo has high hopes for OX124, which is a high-dose formulation of naloxone, the active ingredient in Emergent BioSolutions’ rescue medicine Narcan. Narcan was approved for prescription use in 2015, followed by a nod in 2023 for a lower-dose over-the-counter version.

OX124 was developed with Orexo’s amorphOX drug delivery technology to compete with other prescription medicines for opioid overdose, where there is a need for more potent and longer-lasting treatment options. Last year, Indivior’s opioid overdose nasal spray Opvee (nalmefene hydrochloride) was approved for prescription use.

Orexo is seeking approval on the strength of data from a pivotal study in healthy volunteers, which found OX124 nasal spray provided a significantly faster and higher absorption of naloxone than intramuscular dosing with an injection reference product. 

Last year, opioid overdose deaths in the U.S. decreased for the first time in five years, falling from 84,181 in 2022 to 81,083 in 2023, according to the CDC.