FDA Declines to Approve Orexo’s Opioid Overdose Drug, Seeks More Information

A seizure of tens of thousands of fentanyl pills by the Drug Enforcement Administration's Rocky Mountain Field Division in a photo released on July 1, 2024. (DEA)

The U.S. Food and Drug Administration (FDA) has rejected Orexo’s application for a new, high-dose drug for reversing opioid overdoses.

Orexo said on July 16 that the FDA issued a complete response letter, seeking an additional “human factors” study and further technical data on its naloxone rescue medication, known as OX124.

The Sweden-based pharmaceutical company said the FDA’s request for additional technical data was “unexpected” and that it’s working with the agency to enable a resubmission.

Orexo submitted the new drug application in September 2023.

The company said it developed OX124 to be absorbed quickly for “high bioavailability” to reverse the effects of synthetic opioid poisoning.

According to the National Institute on Drug Abuse, nearly 108,000 drug overdose deaths were reported in 2022. Of those, more than 81,000 involved opioids, up from about 50,000 in 2019.

The new drug is expected to address the demand for higher naloxone dosages. Synthetic opioids, such as fentanyl, are implicated in about 92 percent of all fatal opioid overdoses.

Last year, the FDA approved the life-saving drug naloxone for over-the-counter (OTC) sale as a nasal spray sold under the brand names NARCAN, made by Emergent Biosolutions, and RiVive, manufactured by Harm Reduction Therapeutics.

“We know naloxone is a powerful tool to help quickly reverse the effects of opioids during an overdose. Ensuring naloxone is widely available, especially as an approved OTC product, makes a critical tool available to help protect public health,” FDA Commissioner Robert M. Califf said in July 2023.

“The agency has long prioritized access to naloxone products, and we welcome manufacturers of other naloxone products to discuss potential nonprescription development programs with the FDA.”

According to Orexo, the company submitted the required technical data in its initial new drug application using data generated during its pilot-scale production.

Earlier this year, the company said it received comments from the FDA about the drug’s instructions, possibly delaying its targeted launch for later this year or early 2025.

Now, Orexo says the FDA is seeking commercial-scale manufacturing data.

“I am impressed by the vigour and agility of the teams in Sweden and the US in addressing FDA’s concerns from April regarding the instructions for use and our ability to complete a new human factors study shortly,” Nikolaj Sørensen, Orexo’s president and CEO, said in a statement on July 16.

“However, I am surprised with the agency’s other requests with regards to additional technical data from final commercial product, but I am confident we can address this efficiently.”

Mr. Sørensen said he believes the medication will reduce the number of opioid-related deaths in the United States and that he and his team are taking action to respond to the FDA request.

The FDA review period after resubmission of a new drug application could take up to six months.