FDA Rejects Orexo's Nasal Spray for Opioid Overdose Again

The FDA has denied approval for Orexo's OX124, a nasal spray designed to combat opioid overdoses, marking the second rejection in 15 months. In its complete response letter (CRL), the FDA cited two main issues with Orexo’s application, one of which was unexpected. The U.S. regulatory body is demanding more technical data on the final commercial product. Initially, Orexo had submitted data from pilot scale manufacturing, which they believed should suffice for approval. However, the FDA insists on receiving information derived from commercial scale manufacturing processes.

Orexo's CEO, Nikolaj Sørensen, expressed surprise at this technical data request but remains optimistic about addressing it efficiently. Importantly, the FDA is not requiring Orexo to conduct another clinical trial. Instead, they need the results from an additional "human factor" study to confirm that patients can correctly use the product. Orexo reported that they have already completed this study after the agency had flagged this deficiency in an April discussion.

OX124 is a high-dose formulation of naloxone, the active ingredient in Narcan, a well-known rescue medication manufactured by Emergent BioSolutions. Narcan has been available for prescription use since 2015, and a lower-dose over-the-counter version received approval in 2023. Orexo’s OX124 was developed using the company’s amorphOX drug delivery technology, aiming to provide a more potent and longer-lasting treatment option compared to current prescription medicines for opioid overdose. Last year saw the approval of Indivior’s nasal spray, Opvee (nalmefene hydrochloride), for prescription use, highlighting the evolving landscape in opioid overdose treatments.

Orexo is seeking FDA approval based on data from a pivotal study involving healthy volunteers. The study demonstrated that OX124 provided significantly faster and higher absorption of naloxone compared to intramuscular dosing with an injection reference product. This faster absorption could be critical in emergency overdose situations.

Despite these optimistic results, the FDA's request for additional data from commercial scale manufacturing could delay the potential approval and commercial availability of OX124. This setback arrives at a crucial time, as the opioid crisis continues to take a significant toll on public health in the United States. According to the CDC, the number of opioid overdose deaths in the U.S. saw a slight decline from 84,181 in 2022 to 81,083 in 2023, the first decrease in five years.

Orexo remains committed to addressing the FDA's concerns and moving forward with their application. Sørensen's confidence suggests that the company is prepared to meet the regulatory requirements set forth by the FDA, albeit acknowledging the unexpected nature of the additional data request.

The development and approval of effective opioid overdose treatments are vital in the fight against the opioid epidemic. As companies like Orexo continue to innovate and improve upon existing medications, the hope is to provide more effective and accessible solutions for those at risk of opioid overdose. The ongoing efforts to enhance drug delivery technologies and develop more potent formulations underscore the importance of addressing this public health crisis with urgency and precision.