Drugs for Neglected Diseases initiative (DNDi), a product development organization founded to develop drugs for patients suffering from most neglected diseases, seeks NIAID support to develop a new drug to treat visceral leishmaniasis (VL) through collaboration with public and private partners. DNDi manages a portfolio of research and development projects to develop new treatments for VL and proposes a promising project aimed at developing a low cost, tropical climate stable, efficacious and simply reconstituted formulation as an alternative for the current reference treatment, liposomal amphotericin B (AmB). The project is based on use of narrow molecular weight polymers to which AmB is bound. Polymers can prevent the systemic toxicity of AmB to which they are covalently conjugated, still allowing drug intracellular delivery. The research program should result in a complex which combines adequate intracellular delivery of AmB and synergistic immuno-therapeutic activity brought by the polymer. Specifically, DNDi requests NIAID support to achieve the 3 year pre-clinical development objectives for the chosen complex: (1)-to conduct and complete chemical synthesis and lead optimization at laboratory scale testing by 2009;(2)- to conduct and complete biological testing for safety and early stage efficacy by 2009;(3)- to complete additional chemical and biological assessment and submit an IND regulatory file to the Indian authorities in 2010. In 2011, following authorization from the Indian regulatory authorities, DNDi will begin clinical development in India to ensure the registration of this new drug in 2015 VL, a potentially fatal disease, is present in 88 countries, where 350 million people are at risk of infection yet almost all the 500,000 new cases each year arise from recurrent epidemics in poor, rural areas of the Indian subcontinent (India, Nepal, Bangladesh), Brazil, and Sudan. Therapeutic options to treat VL are limited, based on old drugs with limited efficacy and severe side effects or more recent drugs to which patient access is limited by high cost, toxicity or parenteral administration. The proposed project should yield an efficacious treatment with a cost per vial below $2USD (compared to $20USD for the reference treatment) making broad distribution possible;thus, has great potential for positive impact on public health.
