FDA rejects Orexo nasal opioid overdose remedy again

Orexo AB has encountered a setback with the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for OX124, a high-dose naloxone rescue medication designed to counteract opioid overdoses. The FDA issued a complete response letter (CRL) to Orexo, outlining the need for further information before the application can proceed.

The CRL specified the necessity for an additional Human Factors (HF) study and more comprehensive technical data related to the final commercial product. Importantly, the FDA did not demand any further clinical or non-clinical studies, which often require extensive time and resources to complete.

Orexo had previously made adjustments to its NDA in response to earlier feedback from the FDA. These adjustments included optimizing the instructions for use and conducting a new HF study, specifically designed to align with FDA standards. Despite these efforts, the request for more technical data from the final commercial product came as an unexpected development for the company. Orexo is now swiftly working to compile and submit the additional data, in close consultation with the FDA, to resolve this issue promptly.

According to Orexo, the type of technical data now requested by the FDA had previously been generated during the pilot-scale manufacturing phase and was included in the initial NDA submission. However, the FDA is now seeking additional data from the established commercial-scale manufacturing process.

OX124 is developed using Orexo's proprietary drug delivery platform known as amorphOX. This technology is distinguished by its physical and chemical stability, even in elevated temperatures. The formulation comprises a combination of a drug, carrier materials, and possibly other excipients such as a permeability enhancer.

Orexo has a history of working with the FDA; back in 2013, the agency approved Orexo’s Zubsolv for the treatment of opioid addiction. Zubsolv is a sublingual tablet that combines buprenorphine and naloxone, offering a treatment option for those battling opioid dependency.

In light of the recent CRL, Orexo remains committed to addressing the FDA’s requests and advancing the approval process for OX124. The company acknowledges the unexpected nature of the current situation but is focused on meeting the regulatory requirements to bring this critical rescue medication to market.

Overall, while the FDA’s request for additional technical data from commercial-scale manufacturing presents a hurdle, Orexo's prior experience with regulatory approvals and its ongoing efforts to meet FDA standards suggest a path forward. The successful approval of OX124 would mark another significant contribution by Orexo in the battle against the opioid crisis, expanding the options for emergency overdose interventions.

Orexo continues to work diligently to ensure that all necessary data and studies are completed to the satisfaction of the FDA, reinforcing their commitment to addressing opioid overdose emergencies.