Health, Defense Secretaries Pave Way for Ketamine Drug

At first, the Federal Register notice set off alarm bells: The secretaries of health and defense were collaborating on emergency use of medical countermeasures for U.S. military forces — but they didn’t specify why.

In July, Defense Secretary Pete Hegseth determined there was a military emergency — or significant potential for one — involving a higher risk of a chemical, biological, radiological, or nuclear attack on U.S. forces.

The next month, HHS Secretary Robert F. Kennedy Jr. determined that circumstances existed to justify emergency use of drugs, specifically targeting moderate-to-severe acute pain caused by such attacks.

The notice, posted Sept. 3, left many scratching their heads. Then, a few days later, a press release appeared: Singapore-based iX Biopharma announced that the U.S. government cleared an emergency use pathway for its sublingual ketamine product Wafermine.

Earlier this year, the company received a $41 million sole-source contract from Trump’s Defense Department for the development of the compound, which in part funded a phase III trial that’s still ongoing.

That contract came out of the blue, according to a source who did not want to be named but described the arrangement as “bizarre.”

“The accelerated EUA [emergency use authorization] strategy and sole-source award deserve transparency and scrutiny,” Terry Adirim, MD, MPH, MBA, former acting assistant secretary of defense for health affairs, told MedPage Today.

Adirim questioned why the drug needs to “move through an emergency use pathway before the normal phase III studies and approval process are complete.” Though ketamine is a known commodity, this formulation is not, she said.

She added that there “may be legitimate operational reasons for wanting to use it,” since sublingual ketamine is “easy to carry, and needle-free for use in large-scale combat” — but emphasized that “those reasons should be clearly explained.”

“I would also want to see the government’s justification for the $41 million sole-source development agreement,” she added.

Military sources said that the contract isn’t typical; it’s an “Other Transaction Agreement” rather than a competitively bid procurement. These agreements give military leaders considerable flexibility, but federal law still instructs that competitive procedures be used as often as possible.

It’s also unclear as to whether the notice pertains only to this ketamine product, or to others as well. Adirim questioned whether the increased risk is related to a potential escalation of the war in Iran.

A request for comment from HHS went unreturned as of press time.

Ketamine has a long history of battlefield use, and military guidelines currently recommend it in its intravenous, intramuscular, and intranasal forms for significant battlefield pain. It has many advantages over opioids, including that it causes less respiratory depression and low blood pressure, which is important for casualties with hemorrhage, shock, or respiratory compromise.

This newer, sublingual formulation hasn’t been studied as thoroughly, Adirim noted, and it may require a higher dose given the way it’s metabolized. That’s why the results of the phase III study will be important.

The Federal Register notice doesn’t grant an EUA for sublingual ketamine; it simply establishes a pathway for the company to apply for an EUA, Adirim noted. “The FDA still has to review the application and decide whether it meets the statutory standard,” she said.

The pathway invoked by Kennedy doesn’t have much precedent. The only other time it occurred was in 2018, during the first Trump administration, for freeze-dried plasma to treat uncontrolled hemorrhage in combat casualties, according to Adirim and iX Biopharma.

In its press release, the company said it plans to complete its EUA submission for the sublingual ketamine product by the end of this year.

If it gets the EUA, the company said it can “begin generating revenue ahead of full FDA approval and in parallel with” its ongoing phase III program.