Ophirex Publishes Data from Phase 2 BRAVIO Trial Evaluating Intravenous Followed by Oral Varespladib for Snakebite
Trial evaluated varespladib administered after antivenom across multiple snake species in India and the United States
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Trial evaluated varespladib administered after antivenom across multiple snake species in India and the United States
Clinically important signals of benefit observed in patients bitten by kraits and copperheads
CORTE MADERA, Calif., Sept. 22, 2026 (GLOBE NEWSWIRE) — Ophirex, Inc., a Public Benefit Corporation developing novel treatments for snakebite envenomation, today announced the publication of results from the Phase 2 BRAVIO clinical trial in PLOS Neglected Tropical Diseases. The trial evaluated the efficacy and safety of intravenous sodium varespladib followed by oral methyl varespladib, added to standard antivenom therapy, in patients with snakebite envenomation in India and the United States.
The multicenter, randomized, double-blind, placebo-controlled study enrolled 140 hospitalized patients (139 analyzed) across 18 sites in India and the United States, assigning them in a 1:1 ratio to varespladib or placebo in addition to antivenom. Sites were selected to provide broad geographic representation and capture a diverse range of medically important snake species. Enrolled patients were bitten by a range of elapids and vipers, including kraits, Russell’s vipers, rattlesnakes and copperheads.
Varespladib is a small-molecule inhibitor of snake venom secretory phospholipase A2 (sPLA2), a major snake venom toxin present in at least 95% of venomous snake species worldwide with multiple effects, including neurotoxicity, local tissue injury and hemorrhage. Varespladib is being studied as a broad-spectrum snakebite treatment that binds to and inactivates sPLA2 regardless of the snake species, neutralizing its activity and mitigating downstream toxic effects.
In BRAVIO, on average, varespladib was initiated 7.3 hours after the snakebite and 3.3 hours after antivenom. The trial did not meet its prespecified primary endpoints of time to recovery of 5-second head-lift for elapid envenoming and area under the curve (AUC) from baseline to Day 14 of a 3-item Snakebite Severity Score (SSS) composed of the local wound, hematologic, and neurologic subscores for viper envenoming.
Varespladib did demonstrate a signal of benefit in patients bitten by snakes with well-defined sPLA2-driven toxicities, including elapids and copperheads. Among elapid patients, primarily those bitten by kraits, varespladib-treated patients (n=24) spent approximately half as much time on mechanical ventilation (21 hours vs. 40 hours) and experienced 36% lower illness severity over the first week. Copperhead patients treated with varespladib (n=12) experienced a 43% reduction in illness severity over the first two weeks.
“The study drug was initiated an average of seven hours after snakebite and following the administration of antivenom, making it difficult to measure the true effect of sPLA2 inhibition,” said Charles J. Gerardo, MD, co-lead author and Professor at Duke University Hospital. “Giving antivenom up front was necessary due to the severity of snakebite envenomation within the trial. Nonetheless, varespladib, as a late adjunctive therapy, was associated with clinically meaningful signals of benefit in krait and copperhead patients. These results are consistent with the known mechanism of action of varespladib and point to the need for further studies.”
Varespladib was well tolerated across the study population, and no serious adverse events were reported in varespladib-treated patients.
“The results in krait- and copperhead-bite patients are aligned with the benefits observed in animal experiments,” said Timothy Platts-Mills, M.D., MSc, Chief Medical Officer of Ophirex. “To study the effects of varespladib in humans in a use case more similar to its intended use – as an oral rescue treatment administered at the time of bite, before antivenom – Ophirex is continuing the study of varespladib via the FDA’s Animal Rule, under which efficacy data from adequate and well-controlled animal studies form the basis for approval. This is the appropriate regulatory pathway in instances when human efficacy trials are unethical or infeasible. If approved, we anticipate additional post-approval clinical studies will evaluate the effects of prehospital and early in-hospital treatment.”
Snakebite envenomation globally results in 80,000-138,000 deaths and 400,000 cases of permanent disability each year primarily in low- and middle-income countries, with more than 50,000 deaths per year in India alone.i The majority of deaths occur before patients reach a hospital.ii Despite this toll, antivenom remains the only pharmacologic treatment available, requiring intravenous administration in a medical setting. Delays in antivenom administration are a major contributor to poor outcomes following snakebite.
“There is a significant unmet need for a snakebite treatment that can be administered at the time of bite to immediately inhibit the effects of snake venom,” said Jeremy Gowler, CEO of Ophirex. “We are committed to continuing varespladib’s development, and efficacy studies in animals are underway.”
The paper, Adjunctive Varespladib After Antivenom Administration for Snakebite: a Phase II Randomized Clinical Trial, is available online here.
The company plans to publish subgroup analyses of varespladib administration in patients bitten by krait and copperhead snakes in the next few months.
About Ophirex
Ophirex is a Public Benefit Corporation developing varespladib, a first-of-its-kind oral rescue treatment for snakebite that, if approved, could be taken at the time of bite. Varespladib is a small-molecule inhibitor of snake venom secretory phospholipase A2 (sPLA2), a class of toxins present in the venom of more than 95% of venomous snake species. It rapidly inhibits sPLA2 activity and mitigates downstream toxic effects. Varespladib has received FDA Orphan Drug, Pediatric Rare Disease and Fast Track designations, and is being developed with support from the Defense Health Agency’s Small Business Innovation Research (DHA SBIR) program and the Warfighter Protection and Acute Care (WPAC) team under the Broad-Spectrum Snakebite Antidote (BSSA) program. Additionally, varespladib has received Minor Use in Major Species (MUMS) designation from the FDA’s Center for Veterinary Medicine for the treatment of snakebite in dogs when antivenom is not immediately available. For more information, visit www.ophirex.com.
The information contained in this press release does not necessarily reflect the position or the policy of the U.S. Government and no official endorsement should be inferred.
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i Warrell DA, Williams DJ. Clinical aspects of snakebite envenoming and Its Treatment in Low-Resource Settings. Lancet. 2023;401(10385):1382-1398. doi:10.1016/S0140-6736(23)00002-8.
ii Mohapatra B, Warrell DA, Suraweera W, et al. Snakebite mortality in India: a nationally representative mortality survey. PLoS Negl Trop Dis. 2011;5(4):e1018. Published 2011 Apr 12. doi:10.1371/journal.pntd.0001018.
