A major impediment to eliminate lymphatic filariasis and onchocerciasis is the lack of effective short-course macrofilaricidal drugs or regimens that are proven to be safe for both infections. In this study we tested oxfendazole, an anthelmintic shown to be well tolerated in phase 1 clinical trials.
In vitro
, oxfendazole exhibited modest to marginal motility inhibition of adult worms of
Onchocerca gutturosa
, pre-adult worms of
Onchocerca volvulus
and
Onchocerca lienalis
microfilariae.
In vivo
, five days of oral treatments provided sterile cure with up to 100% macrofilaricidal efficacy in the murine
Litomosoides sigmodontis
model of filariasis. In addition, 10 days of oral treatments with oxfendazole inhibited filarial embryogenesis in patent
L
.
sigmodontis
-infected jirds and subsequently led to a protracted but complete clearance of microfilaremia. The macrofilaricidal effect observed
in vivo
was selective, as treatment with oxfendazole of microfilariae-injected naïve mice was ineffective. Based on pharmacokinetic analysis, the driver of efficacy is the maintenance of a minimal efficacious concentration of approximately 100 ng/ml (based on subcutaneous treatment at 25 mg/kg in mice). From animal models, the human efficacious dose is predicted to range from 1.5 to 4.1 mg/kg. Such a dose has already been proven to be safe in phase 1 clinical trials. Oxfendazole therefore has potential to be efficacious for treatment of human filariasis without causing adverse reactions due to drug-induced microfilariae killing.