references
R&D MODEL & PORTFOLIO
pre-clinical development in 2015. Additional drug candidates have come from the drug discover y programmes of GSK/Dundee Drug Unit (two classes), and Celgene (one class). These six classes are also undergoing testing in animal models of CL. The three classes from the DNDi series have already shown efficacy against L. major in a mouse model of infection, with the aminopyrazole class showing sterile cure in animals. This is the first time this has been observed with a drug candidate. The NTD Drug Discovery Booster, a multilateral experiment launched in 2015, aims to speed up the discovery of new compounds for leishmaniasis and Chagas disease. The lack of clinical markers of disease, and of animal models capable of accurately predicting the translation of drugs from laboratory to patient, has proven to be a major obstacle in developing new drugs for Chagas disease.
A two-pronged approach aims to This increased number of comdevelop direct-acting or indirectpounds in development has resulted acting compounds for treating in a concomitant increase in the filarial diseases. Emodepside, used number of clinical trials. At the end in veterinary healthcare, began of 2015 more than 30 clinical trials its clinical evaluation in healthy were in preparation, on-going, or volunteers in 2015 as a potential reporting results worldwide. treatment for onchocerciasis. The extension of DNDi’s portfolio Additional NCEs are being sought with the new Business Plan 2015by screening focused libraries 2023 (see p. 6) led to the inclusion of with known anthelmintic activity two new diseases. Fosravuconazole, from animal health companies and already available to DNDi because repurposing libraries from human of its previous evaluation for Chagas health companies. Although drug disease, is the most promising drug repurposing is high risk, the wealth candidate for fungal mycetoma and DND i will begin recruiting of information available for drugs which have already undergone 130 patients in Sudan in the first ever randomized clinical trial to clinical development can speed up be undertaken for eumycetoma. the development process drastically, A combination of sofosbuvir with and new treatments reach patients ravidasvir will be evaluated in faster. A macrofilaricide which indirectly leads to the death of the DNDi 750 patients in Malaysia and South parasite by killing its Wolbachia East Thailand as a potential public health Asia symbiont entered the development tool to treat Hepatitis C. pipeline in 2015.
29 ongoing clinical studies in 2015, on 4 continents, for 7 diseases
Phase I Phase II Phase III Phase IV
3 STUDIES
11 STUDIES
10 STUDIES
5 STUDIES
Efficacy studies with fexinidazole in human African DNDi trypanosomiasis (HAT) patients in the Democratic DRC Republic of Congo and Central African Republic will ultimately collect information from 750 adults and children above the age of 6 years with both stages of gambiense disease, including an evaluation of its ease of use under real-life conditions. A later study will examine its efficacy in patients with rhodesiense HAT. Fexinidazole is also being investigated for treating patients with the related kinetoplastid diseases – leishmaniasis and Chagas disease. A combination of fexinidazole and miltefosine for the treatment of DNDi Africa visceral leishmaniasis (VL) patients in eastern Africa could be the first oral-only combination therapy for VL: an allometric dosing study of miltefosine to address drug underexposure in children was undertaken in 2015. Twelve month follow-up of efficacy and safety data of fexinidazole in adult Chagas disease patients was concluded in 2015, with the results expected in early 2016. A planned study in 270 adult patients with chronic
DNDi Chagas disease aims to determine if the safety and Latin America tolerability issues of benznidazole can be managed by
