Ophirex Reports Phase 2 Data on Varespladib for Snakebite Treatment in BMJ Global Health

Ophirex, Inc., a Public Benefit Corporation based in Corte Madera, California, is actively developing an innovative oral treatment for snakebite victims worldwide. Recently, the esteemed journal BMJ Global Health featured the company’s BRAVO trial, which evaluates the efficacy and safety of oral varespladib, a groundbreaking therapeutic candidate. This small synthetic molecule directly inhibits secretory phospholipase A2 (sPLA2), an enzyme found in over 95% of snake venoms. The oral formulation aims to serve as an immediate intervention, potentially becoming the first-ever field therapy for snakebite envenoming.

The BRAVO trial (Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite) is a multi-center, randomized, double-blind, placebo-controlled Phase 2 study designed to assess the safety, tolerability, and efficacy of varespladib. The trial included 95 participants from the United States and India, who were given either varespladib or a placebo in addition to the standard care, which typically involved antivenom for 93 of the 95 patients.

According to Timothy Platts-Mills, M.D., MSc, Chief Medical Officer of Ophirex, the BRAVO trial is pioneering in its approach. It is the first clinical trial to evaluate a direct toxin inhibitor for snakebites and to enroll patients bitten by various snake species across two continents. Although the study did not achieve its primary endpoint, there was a promising indication of benefit for the group treated within five hours of the bite. This suggests that varespladib could be a valuable early treatment option, potentially serving as a field treatment.

In the subgroup of patients treated early, significant differences were noted in key outcomes such as reduced illness severity during the first week, higher rates of complete recovery, and improved patient-reported function. The BRAVO trial results also indicate that varespladib is safe and well-tolerated, reinforcing its potential as a reliable treatment for snakebite.

Charles J. Gerardo, M.D., Professor and Chair for the Department of Emergency Medicine at Duke University, highlighted the limitations of antivenom, the current standard of care for snakebites. These limitations include the need to match the antivenom to specific snake types, the risk of anaphylaxis, and the requirement for intravenous administration in a hospital setting. Given that 75% of venomous snakebite deaths occur before the victim reaches a medical facility, there is a critical need for an effective early treatment. Dr. Gerardo emphasized that early treatment results in better patient outcomes, making these BRAVO trial findings highly encouraging.

Dr. Suneetha D.K., Professor and Head of Internal Medicine at Mysore Medical College and Research Institute in Mysuru, noted that India bears the highest burden of snakebite deaths worldwide, with 97% occurring in rural areas far from medical care. She expressed optimism that oral varespladib, in addition to standard care, could enable treatment at the time of the bite or while en route to advanced care, significantly improving patient outcomes and healthcare systems.

Matthew R. Lewin, MD, PhD, Chief Scientific Officer and Founder of Ophirex, reiterated the company's commitment to developing varespladib as an oral field treatment. He emphasized that the BRAVO trial findings support this vision, and the company plans to apply these insights to ongoing studies, addressing the long-unmet need for a field treatment for snakebites.

Ophirex is dedicated to creating a first-of-its-kind oral solution for snakebite envenoming. With approximately 500,000 annual cases of snakebite envenoming resulting in death or permanent disability, the need for an effective treatment is urgent. Antivenom, which has been the standard of care for over a century, is limited by its requirement for hospital administration. Ophirex aims to bridge this gap with varespladib, providing a critical early intervention that could improve survival rates and patient outcomes. The company continues to advance its research and development efforts, with the ultimate goal of transforming snakebite treatment globally.