Authors

S Specht¹;  ¹ Drugs for Neglected Diseases initiative (DNDi), Switzerland

Discussion

Twenty diseases are recognized as neglected tropical diseases (NTDs) by World Health Assembly resolutions, including human filarial diseases. The end of neglected tropical diseases is now firmly embedded within the Sustainable Development Goals for 2030, under target 3.3. Filarial diseases still affect an estimated 200 million people worldwide and global efforts undertaken in recent decades have enabled elimination of filariasis as a public health problem. It is recognized that new drugs or drug regimens that kill or permanently sterilize adult filarial worms would significantly improve elimination timelines and accelerate achievement of the program goal of disease elimination. Drug development is, however, handicapped by high attrition rates, and many promising molecules fail in preclinical development or in subsequent toxicological, safety and efficacy testing; thus, research and development (R&D) costs are, in aggregate, very high. Drug discovery and development for NTDs is largely driven by unmet medical needs put forward by the global health community; the area is underfunded and since no high return on investment is possible, there is no dedicated drug development pipeline for human filariasis. Product development partnerships between the private sector, academic institutions and NGO´s are a vital part of enabling drug development in an otherwise underfunded area. In addition, repurposing existing drugs is one approach to filling the drug development pipeline for human filariasis. While the de novo development of anthelmintics is commercially not attractive for human use, development of new drugs for animal health is (relatively) financially rewarding and therefore much better supported and further advanced. Furthermore, drug repurposing typically has a higher chance of success with an already proven drug target in nematodes of veterinary importance. Some impressive examples demonstrate successful repurposing of veterinary drugs for human use, including benzimidazoles, IVM, praziquantel, moxidectin and triclabendazole. This approach has also been adopted by the DNDi, which is currently investigating emodepside (in collaboration with Bayer AG) and ABBV-4083 (a tylosin derivative, jointly developed in collaboration with the Anti-Wolbachia (AWOL) consortium and the pharma partner AbbVie). The third lead compound is the off-patent veterinary product oxfendazole for potential human use. Here we present a project update and discuss the considerations to enable patient`s access to new medicines.