R&D MODEL & PORTFOLIO
What are the current treatments and their limitations?
Current treatments for onchocerciasis and lymphatic filariasis are based on repeated mass drug administration (MDA) of antiparasitic drugs through programmes directed by the WHO. WHO recommends MDA for onchocerciasis at least once yearly for 10-15 years, and for lymphatic filariasis once yearly for at least five years. The drugs used in MDA programmes are ivermectin for onchocerciasis; albendazole for lymphatic filariasis; and albendazole plus either ivermectin in areas where onchocerciasis is also endemic (i.e. African countries), or diethylcarbamazine (DEC) in areas where onchocerciasis is not co-endemic (i.e. non-African countries). A bite from an infected insect allows filarial larvae to pass into the blood and migrate through the human body. These mature into adults that produce microfilariae, which the insect ingests during a blood meal, and the cycle goes on. MDA drugs can prevent this vector-borne transmission for several months by killing mainly the microfilariae, and inducing a temporary sterilization of adult worms. However, because adult worms (macrofilariae) continue to live in the body, they eventually produce new microfilariae, often before the next MDA, thus requiring repeated MDAs for several years to decades. Ivermectin treatment is safe and has been used widely in MDA programmes. However, the use of ivermectin in patients co-infected with high levels of Loa loa microfilaria in the blood can result in safety issues such as the occurrence of encephalopathy that can be fatal if not properly managed. Additionally, a suboptimal response to ivermectin in patients with onchocerciasis has been reported which may be a sign of resistance development. Furthermore, the morbidity associated with onchocerciasis and LF infection (itching, dermatitis, lymphedema, and blindness) are only partially improved or prevented and require repeated treatment with the current drugs.
infected worldwide, with 99% cases in
265,000 blinded 169 million
were estimated at risk in 2014
and more than 4 million suffering from severe itching
Over billion people at risk worldwide, 57% in South East Asia region Over million suffering from clinical illness (19.4 million with hydrocele, and 16.6 million with lymphedema)
WHAT IS DNDi DOING TO ADDRESS UNMET TREATMENT NEEDS?
DNDi’s strategy is to develop a new compound with macrofilaricide activity (to kill adult worms) for use as a safe and field-adapted macrofilaricidal drug for patient case management and possibly later MDA if needed. As a medium-term strategy, DNDi is assessing emodepside which is commercialized by Bayer under license from Astellas as an anthelmintic veterinary drug for cats and dogs in combination with praziquantel (Profender®) and in combination with toltrazuril (Procox®). DNDi has an agreement with Bayer to develop emodepside for the treatment of onchocerciasis. Other compounds targeting Wolbachia, a worm symbiotic bacteria present in the parasites causing onchocerciasis and LF, will also be explored. As a long-term strategy, DNDi is assessing additional opportunities through an active screening programme of drug compounds emanating from animal health/pharmaceutical companies and academic institutions, with the goal of selecting one or two candidates to move into clinical development. DNDi aims to deliver a safe, efficacious, affordable, and field-adapted macrofilaricidal drug for onchocerciasis and/or lymphatic filariasis for the treatment of patients, and as a possible alternative in mass drug administration programmes.
42 › DNDi Annual Report 2015