Development of emodepside as a possible adulticidal treatment for human onchocerciasis-The fruit of a successful industrial-academic collaboration.

Abstract

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer-DNDi partnership is an outstanding example of "One World Health," in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area.

• Authors: Jürgen Krücken, Lindy Holden-Dye, Jennifer Keiser, Roger K Prichard, Simon Townson, Benjamin L Makepeace, Marc P Hübner, Steffen R Hahnel, Ivan Scandale, Achim Harder, Daniel Kulke
• Journal: PLoS pathogens (PLoS Pathog) Vol. 17 Issue 7 Pg. e1009682 (07 2021) ISSN: 1553-7374 [Electronic] United States
• PMID: 34293063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antiparasitic Agents
• Depsipeptides
• emodepside

Topics

• Antiparasitic Agents (therapeutic use)
• Depsipeptides (therapeutic use)
• Drug Development (methods)
• Humans
• Onchocerciasis (drug therapy)