FDA Accepts Orexo's IZIPRY Naloxone Powder, Sets March 2027 Decision

The Food and Drug Administration has accepted for review Orexo's resubmitted application for IZIPRY, a high-dose naloxone nasal powder, and set a March 29, 2027 target action date, the Swedish drugmaker said Thursday. The agency confirmed a six-month review timeline, the standard clock for a resubmitted application that answers a prior rejection.

If approved, IZIPRY would be the first naloxone product sold in the United States as a nasal powder rather than a liquid spray. Orexo built it on its AmorphOX delivery platform, which the company says produces rapid absorption and higher bioavailability than conventional liquid nasal formulations.

"Confirmation of the March 29, 2027 PDUFA target action date marks another important milestone toward potential FDA approval of IZIPRY," said Nikolaj Sørensen, Orexo's president and chief executive. "Acceptance for review confirms that the application contains the information needed for the FDA to assess whether the issues previously raised have been adequately addressed."

A second pass at the agency

The filing is Orexo's second attempt. The FDA issued a complete response letter in July 2024 asking for commercial manufacturing data, an additional human factors study and further technical information — questions about whether the finished product would perform the way clinical batches had, not about whether the drug reversed overdoses. Orexo resubmitted the application on September 29.

Acceptance for review means the agency considers the file complete enough to evaluate. It does not signal how the review will end. The FDA can still approve the product, approve it with conditions, or issue another complete response letter before the March date.

The company said it is still looking for a commercialization partner to handle United States market access, and no partner has been announced.

Why a powder, and why dose

Orexo's argument rests on two shifts in the overdose landscape. The first is dose. Since illicit supply moved from heroin to fentanyl, researchers have documented rising rates of repeat naloxone administration by both lay bystanders and emergency medical crews, and the Drug Enforcement Administration has warned that fentanyl combined with emerging synthetic opioids may require several doses to reverse. A formulation that delivers more naloxone per actuation is intended to shorten the gap between overdose and restored breathing.

The second is temperature. Liquid naloxone sprays are subject to freezing, which matters for a rescue drug stored in a patrol car, an ambulance compartment, a syringe exchange bag or an unheated vestibule in a northern winter. Orexo describes its dry powder as stable and usable in freezing conditions, a claim the agency will have reviewed as part of the stability data.

None of that has been independently tested in a head-to-head field comparison. The published evidence on repeat dosing describes how often multiple doses are used, not how a higher-dose powder changes outcomes in a parking lot at 2 a.m.

A market that changed under it

When Orexo first filed, naloxone was still moving from prescription-only to over-the-counter. Narcan became the first nonprescription nasal spray in 2023, followed by RiVive and then Rextovy, Amphastar's 4-milligram spray. Manufacturers have also pushed dose strengths higher within the spray category, and Scienture markets Rezenopy as the highest-dose naloxone nasal spray the agency has cleared.

That leaves IZIPRY competing on delivery format and on price — a fight that increasingly runs through public purchasers. State health departments, county health systems, school districts and harm reduction programs now buy naloxone in bulk, often with settlement money, which makes the cost of a kit a central selling point.

A March approval would land about two years and eight months after the July 2024 rejection. Whether a distributor is in place by then is a separate question, and one the company has not answered publicly.

People seeking help for opioid use disorder can find medication-assisted treatment programs and naloxone access points through federally maintained directories.