Neglected Diseases
Snakebite envenoming results from the bite of a venomous snake, and if not treated quickly and effectively can result in life-long disability, or lead to amputation or death.
Snakebite envenoming is prevalent in tropical and sub-tropical regions in Africa, Asia, Oceania and Latin America. Snakebite envenoming was included in the G-FINDER report for the first time in the 2019 report.
Antibody-based antivenoms are the mainstay of snakebite envenomation treatment. These are effective, life-saving products if administered at the right time, in the correct dose, and for the right species. However, manufacturing immunobiologicals is expensive and complex, requiring harvesting and purifying immune-rich plasma from hyper-immunised large animals. The production of quality antivenom is hampered by the lack of a universal regulatory framework and appropriate reference standards, and geographical variations in the venom pool. Conventional anti-venoms are liquid or freeze-dried formulations requiring skilled professionals for administration, making them inappropriate in resource-limited settings. There is an urgent need to develop next-generation antivenom products that are safe, effective, geography-appropriate or polyvalent, and affordable for the low-income settings where they are most needed. The current research efforts include recombinantly expressed human antibodies and antibody fragments and small molecule therapeutics (SMT), including oral formulations. One such SMT – varespladib-methyl, is currently in a Phase II clinical trial.
The BRAVO Phase II clinical trial of the drug Varespladib-methyl, a repurposed PLA2 inhibitor, was completed in June 2023, after demonstrating activity against anti-coagulant PLA2 toxins and procoagulant venom toxins in preclinical studies. The Novel ICP-AVRIUOP Sri Lankan polyspecific antivenom, with neutralizing abilities against the venom of four snake species highly prevalent in Sri Lanka, is currently registered for two Phase II/III studies testing several different dosages and efficacy relative to the Indian AVS. Preclinical research is being conducted on monoclonal antibody-based candidates, a potentially more efficient, tailored, and less immunogenic alternative to traditional plasma-derived antivenoms. These include the broad spectrum human monoclonal antibodies (IgG), developed by Centivax, which has a clinical trial scheduled to launch by the end of 2023.