Varespladib for snakebite envenoming: insights from therapeutic development and clinical trials

Abstract

ABSTRACT Introduction Snakebite envenoming (SBE) causes significant worldwide morbidity and mortality. Patients often face barriers to and delays in accessing antivenom, an effective yet time-sensitive treatment. Finding alternative drugs that could be administered early has the potential to improve SBE outcomes. Phospholipases A2 (PLA2s) are a group of toxins that are common in snake venoms and responsible for many life- and limb-threatening toxicities. Varespladib is an investigational small molecule that broadly inhibits PLA2s and can be given orally or intravenously. Areas covered Preclinical and clinical evidence for the use of varespladib in SBE. We review in vitro studies, animal studies, human safety and tolerability data and the two randomized control trials of varespladib for treatment of SBE. Expert opinion There is strong preclinical evidence that varespladib can prevent and treat severe toxicity in animal models of SBE. In two clinical studies in patients with SBE, varespladib has been safe and well tolerated. Clinical evidence from these studies supports further evaluation of varespladib as an in-hospital treatment administered, with encouraging signals from Agkistrodon contortrix (copperhead), Micrurus fulvius (eastern coral snake), and Bungarus spp (krait). Additional studies may provide insight into the benefit of varespladib as a time-of-bite treatment in specific regions.