U.S. Navy Lt. Cdr. Riley Tedrow, an entomologist with 3rd Medical Battalion, 3rd Marine Logistics Group, holds a Hime habu during a joint preventive medicine training at Jungle Warfare Training Center, Camp Gonsalves, Okinawa, Japan, May 5, 2026. (Jonathan Rodriguez Pastrana/U.S. Marine Corps)
A California company partnering with the Pentagon to develop an antidote for venomous snakebites is in animal trials to gauge the drug’s suitability for humans after clinical trials fell short but showed promise.
Ophirex Inc. expects the drug will be ready by 2028, four years beyond its first hopeful estimate, according to a company executive.
The Pentagon through the Army and Defense Health Agency between 2022 and 2025 has partly funded the project with $34 million and supported the company’s application to test the drug, varespladib, under the Food and Drug Administration’s Animal Rule.
“The Animal Rule is the most viable, scientifically sound pathway to evaluate this treatment and meet the urgent material needs of the warfighter,” according to a statement from DHA spokesman Peter Graves by email June 5.
“Varespladib remains a key part of our portfolio because an oral, field-ready snakebite rescue treatment is critical for protecting the Joint Force operating in austere environments,” the statement reads.
Animal testing is necessary, according to Ophirex chief operating officer Rebecca Carter, because two trials so far with human subjects could not get close enough in time to an actual snakebite to demonstrate the drug’s effectiveness.
Ophirex obtained FDA approval for animal testing in December, according to a company news release Dec. 11.
Studies in animals that mimic snakebite in humans “are underway” to determine the effective dose of varespladib, Carter said in a Zoom call April 28.
A Taiwan habu is displayed during a specialized snake handling course at Kadena Air Base, Okinawa, Japan, April 28, 2026. The venomous species poses a significant environmental hazard in parts of Okinawa. (Amy Kelley/U.S. Air Force)
“The Animal Rule in the United States is set up by Congress and by the FDA for situations where a normal clinical trial is not ethical and not feasible,” Carter said. “I cannot take you to the hospital, recognize you’ve been bitten by a snake, and then withhold care from you so that I can enroll you in my study.”
Substituting varespladib for antivenom, the standard treatment for snakebite patients, is not an option.
The FDA Animal Rule since 2022 “applies only to drugs and biological products that are intended to ameliorate or prevent serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic chemical,” the FDA website states.
The FDA did not respond to questions and an interview request submitted via its website in May.
Varespladib alone does not inhibit all snakebite toxins, but studies show it works against sPLA2, a toxic enzyme present in more than 95% of the world’s venomous snakes, according to Ophirex.
The drug proved inconclusive in clinical trials in India and the United States: BRAVO, from August 2021 to June 2023, and BRAVIO, from May 2023 to February 2025, according to reports on ClinicalTrials.gov.
“Both were proof of concept studies; we did not hit the primary endpoint in either study,” Carter said. “However, both studies had good indications that we were on the right track.”
In both trials, snakebite victims — 95 in BRAVO and 139 in BRAVIO — received antivenom and either varespladib or a placebo hours after being bitten.
The drug failed to significantly reduce snakebite severity, according to the BRAVO results published in October 2024.
But the 29 researchers behind BRAVO — including Carter, Ophirex cofounder Dr. Matthew Lewin and six other Ophirex colleagues -- reported what they called a “signal of benefit,” a small result they found worth pursuing further.
Among 37 patients treated with either varespladib or a placebo within five hours of a bite, those who received varespladib suffered less in the first week and were more likely to recover fully, according to the published results.
Researchers showed in small studies of animals in 2018 and 2023 that varespladib could rescue envenomed pigs. Under the Animal Rule those results — not the failed clinical trials — provide evidence that varespladib may be effective in humans if given as soon as possible.
In the 2023 study by Lewin, Carter and nine others, all 13 pigs treated with varespladib survived Australian taipan venom. The drug was administered in variable doses at 15 and 45 minutes after the venom.
Three envenomed animals not treated with varespladib died.
