Moxidectin: new data support a vital role in the endgame on river blindness

TDR news item
24 January 2018

The results of a large TDR-managed phase 3 trial of treatments for river blindness conducted in the Democratic Republic of the Congo, Ghana and Liberia are now published. They confirm that moxidectin is superior to ivermectin in reducing and maintaining low levels of parasites in the skin. These parasites cause morbidity and are the transmission reservoir. Consequently, moxidectin shows great promise in the endgame on river blindness: a bigger effect on morbidity and transmission and thus shorter time to elimination can be expected if moxidectin is deployed.

Physical examination of a study participant with onchocercal skin disease
Physical examination of a study participant with onchocercal skin disease

River blindness (onchocerciasis) is caused by the parasite Onchocerca volvulus, transmitted by blackflies whose larvae develop in fast flowing rivers. Those infected can suffer from disabling skin and eye symptoms, including blindness. Recent estimates suggest 17 million people are infected and 1.1 million disability-adjusted life-years are lost among the 198 million people living in endemic areas in sub-Saharan Africa, Sudan and Yemen.

From control as a public health problem to elimination of parasite transmission in Africa

Community directed treatment with ivermectin (CDTI) is today the principal tool to control morbidity and parasite transmission. Ivermectin is donated to endemic countries by Merck & Co. CDTI has been very successful in eliminating onchocerciasis as a public health problem and may even have eliminated parasite transmission in some areas in Africa. In the face of these successes, elimination of onchocerciasis is now targeted in Africa.

The African Programme for Onchocerciasis Control (APOC) cautioned, however, that elimination across Africa will require alternative treatment strategies, including drugs with a greater effect on the parasite.

Development of moxidectin for elimination of parasite transmission in Africa

TDR initiated the clinical development of moxidectin in collaboration with Wyeth based on encouraging data from pre-clinical models of onchocerciasis and lymphatic filariasis and the safety data obtained for registration for veterinary use.

Capacity building was an integral part of this TDR-supported research. Besides staff capacity for conducting studies compliant with Good Clinical Practice guidelines, three clinical research centres were created to allow conducting the study in areas without prior CDTI. These centres can now conduct other research for onchocerciasis and lymphatic filariasis control.

Credit: Liberia/Dr Fatorma Bolay; Butembo, DRC/Dr Eric Kanza; Rethy, DRC/Dr Tony Ukety

Following withdrawal of interest of the company which acquired Wyeth, TDR completed the Phase 3 trial alone and searched for a new sponsor willing to submit regulatory filings and to make moxidectin available to countries.

In 2014, TDR licensed all data at its disposal to the non-profit organization Medicines Development for Global Health (MDGH). MDGH raised US$10 million from the Global Health Investment Fund to complete all work required for a New Drug Application with the US FDA. With this application having been designated by the US FDA for priority review, their decision can be expected in the middle of 2018.

For more information, contact Dr Annette C. Kuesel.