references
R&D MODEL & PORTFOLIO
LEISHMANIASIS
WHAT IS DNDi DOING TO ADDRESS UNMET TREATMENT NEEDS?
VISCERAL LEISHMANIASIS
Improved treatment options for VL patients in some areas have already been delivered. DNDi’s short-term approach has been to develop new treatments by combining existing drugs and/or shortening treatment duration in order to increase tolerability, reduce burden on health systems, and offer greater affordability, whilst also preventing or delaying emergence of resistance, and the geographical extension of existing drugs in other countries and regions. In 2010, DNDi and LEAP partners delivered the SSG&PM combination therapy for East Africa, now recommended as first-line treatment for VL in the region. In India, a Phase III trial demonstrated the efficacy of combination therapies of already-registered drugs (see p. 35). In 2014, based on the evidence generated by this trial and one conducted by Sundar et al., the government of India recommended use of single-dose AmBisome® as a first option and paromomycin/miltefosine combination as the second option for treatment instead of using miltefosine as monotherapy, with the same policy change also taken up in Bangladesh and Nepal. DNDi later collaborated with the National Control Programmes of India and Bangladesh, MSF, the Bihar State Health Society, and the Indian Council for Medical Research to assess the effectiveness and safety of these new treatments at the primary healthcare level and facilitate their introduction. In Latin America, DNDi is participating in a study sponsored by the Brazilian Innovation Agency (FINEP) to evaluate the safety and efficacy of Glucantime®, AmBisome®, and amphotericin B as monotherapies, and of AmBisome®/Glucantime® combination to treat VL patients. The national control programme has extended the use of AmBisome® as second-line treatment based on the interim safety data from this trial. In addition, DNDi supports the Leishmaniasis East Africa Platform (LEAP) (see p. 58). A new VL treatment for adults and children based on a new chemical entity would ideally be efficacious against all species of Leishmania in all regions as well as against resistant strains, have at least 95% efficacy, be short course (once a day for 10 days oral; or 3 shots over 10 days), easy to use, compatible for combination therapy, safe in pregnant and breastfeeding women and for immunocompetent/immunosuppressed patients, affordable, and adapted to tropical climates. The TPP for the combination treatment will be reviewed in 2016.
Leishmania and HIV co-infection is a growing problem, difficult to manage clinically due to poor response to treatment with frequent relapses of disease, and is eventually fatal. DNDi is working with partners towards better treatment for HIV/VL co-infected patients in Africa and Asia.
In the medium term, DNDi is assessing the combination of fexinidazole and miltefosine for the treatment of VL patients in eastern Africa. This could be the first oral-only combination therapy for VL. The role of Post-Kala Azar Dermal Leishmaniasis (PKDL, a common complication of VL) in infectivity is poorly understood and treatment options remain limited, requiring long and often repeated courses of treatment including with antimonials. It is a particular problem in Sudan and Bangladesh, and needs to be addressed if VL is to be controlled. DNDi is working with partners to facilitate additional research in epidemiology, diagnosis, pathogenesis, and treatment. DNDi’s long-term strategy for VL is to bring new oral drug candidates into clinical development through its lead optimization programme with the ultimate goal of improving the safety profile and efficacy of the existing tools with a second oral-only combination treatment.
