Orexo nasal opioid overdose rescue drug is rejected by FDA, again

Orexo has received a complete response letter (CRL) from the FDA regarding its NDA for OX124, a high-dose naloxone rescue medication for opioid overdose.

The CRL indicates the need for an additional Human Factors study and more technical data on the final commercial product. The FDA did not request further clinical or non-clinical studies.

In response to earlier comments to its NDA, Orexo optimized the instructions for use and completed a new HF study to meet the FDA's requirements. The request for additional technical data from the final commercial product was unexpected, and Orexo is now working quickly to address this issue in consultation with the FDA.

Orexo says that the type of technical data requested by the FDA had already been generated during pilot-scale manufacturing and was included in the original NDA submission. But, the agency has requested additional data from the established commercial-scale manufacturing. 

OX124 is formulated using Orexo's proprietary drug delivery platform, amorphOX, combined with a high dose of naloxone. AmorphOX is a powder-based technology known for its physical and chemical stability, even at elevated temperatures, and consists of a drug, carrier materials, and optionally, other excipients like a permeability enhancer. The FDA had rejected OX124 once before, in April 2023, citing “technical issues with the equipment used for the secondary packaging process.” 

Back in 2013, the FDA approved Orexo’s Zubsolv for the treatment of opioid addiction. The drug, offered in a sublingual tablet, combines buprenorphine and naloxone.