This project aimed to develop flubendazole as a safe, highly efficacious, and field-usable macrofilaricidal drug candidate for the treatment of onchocerciasis and LF. Flubendazole belongs to the benzimidazole class of molecules. Developed by Janssen Pharmaceuticals (a pharmaceutical company of Johnson & Johnson) in the mid-1970s, it is a potent and efficacious anti-helminthic drug for gastrointestinal nematode infections in swine, poultry, companion animals, and humans. In Europe, flubendazole is marketed for human use as Fluvermal.
In several animal models(1) and in a smallscale human clinical trial for onchocerciasis, in which the drug was administered parenterally,(2) flubendazole showed very specific potency against the adult stage of the worm. Despite this selective potency, it has not been considered as a treatment for filarial infections, as all of the current formulations have very low bioavailability and these oral forms would not provide sufficient systemic exposure.
The first step of this project was to develop, with the help of AbbVie, a new pre-clinical formulation of flubendazole that allows oral absorption.
All data generated by DNDi has been made available to Johnson & Johnson in order to facilitate pre-clinical development of flubendazole as a macrofilaricide. DNDi will continue to support Johnson & Johnson by establishing the pharmacokinetic/pharmacodynamics relationship of flubendazole in different animal models of filariasis.
1) Zahner H., Schares G. (1993) Experimental chemotherapy of filariasis: comparative evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and B. pahangi. Acta Trop 52: 221-66.
(2) Dominguez-Vazquez A. et al. (1983) Comparison of flubendazole and diethylcarbamazine in treatment of onchocerciasis. Lancet 1: 139-43.