Target product profiles for pan-Africa recombinant antivenoms against neurotoxic or hemotoxic and cytotoxic snakebite envenoming

Snakebite envenoming is a neglected tropical disease that yearly causes more than 100,000 deaths worldwide and leaves many more individuals permanently disabled. Because of this enormous human suffering, the World Health Organization (WHO) listed snakebite envenoming as a high-priority neglected tropical disease in 2017, with the goal to reduce mortality and disability caused by snakebite envenoming by 50% by 2030. One of the avenues to reach this goal involves improving current envenoming therapy and developing new types of antivenom products. Today, the only specific treatments for snakebite envenoming are plasma-derived immunoglobulins or fragments of these (traditional antivenoms), which are obtained from large animals, such as horses, hyperimmunized with whole venoms from one or more snake species. Although these traditional antivenoms continue to save lives, they come with some drawbacks, including limited efficacy against certain venoms or toxins, dependence on venoms for production, high production cost, batch-to-batch variation, and the risk of causing adverse immunological reactions upon administration . To overcome these drawbacks, the development of recombinant antivenoms is being investigated. These new types of antivenom are composed of broadly neutralizing, recombinantly produced antibodies or antibody fragments, and, today, several examples of how these can be discovered and optimized have been reported. It is expected that, when properly engineered and developed, recombinant antivenoms have the potential to be safe, effective, and affordable. However, to prove this in a clinical setting, the next step would be to develop and formulate specific antivenom products. To this end, decisions must be taken on desired product characteristics and properties, which can be outlined in so-called target product profiles (TPPs) Such TPPs may also facilitate a regulatory harmonization of recombinant snakebite therapies in a centralized approach through the African Medicines Agency (similar to the European Medicines Agency) and thereby enable/expedite a timely introduction of products throughout sub-Saharan Africa.