To conclude Proof-of-Concept (PoC), Phase II evaluation for E1224 in adults with chronic indeterminate Chagas disease
last phase of drug development
updated 30 Sep 2014
In 2009, DNDi joined forces with Eisai Co. Ltd – the Japanese pharmaceutical company that discovered E1224 – to develop this new chemical entity for Chagas disease. The Phase II proof-of-concept study started in July 2011 in Cochabamba and Tarija, Bolivia, the country which carries the world’s largest Chagas disease burden.
The study evaluated the potential of E1224 as a treatment for Chagas disease and explored promising biomarkers of therapeutic response in Chagas disease (see also Biomarkers project). This randomized, multicentre, placebo-controlled, safety and efficacy study evaluated three oral dosing regimens of E1224 and the standard dosing regimen of benznidazole (5mg/kg/day). The preliminary results, released in November 2013 at ASTMH, indicated that the experimental drug candidate E1224 was effective at clearing the parasite that causes Chagas disease at the end of the treatment course, but there was limited sustained efficacy one year after treatment as a single medication, as well as some safety issues at the highest dose. The current, standard therapy for Chagas, benznidazole, was shown to be very effective in the long term but continued to be associated with safety and tolerability concerns. While development of E1224 as monotherapy has been stopped, the focus has been shifted to exploring its use in a combination treatment for Chagas disease (see new benznidazole regimens and new combinations).
Key findings from the project:
- At treatment completion, PCR-determined eradication rates of the Chagas parasite were 79-91% for E1224; 91% for benznidazole; 26% for placebo.
- 12 months after treatment, 8-31% of patients treated with E1224 maintained parasite clearance compared with 81% with benznidazole and 8.5% placebo.
- 29 September 2009 – Eisai and DNDi enter into a collaboration and license agreement to develop a new drug for Chagas disease
- Special DNDi Clinical Award 2011
- 12 March 2012 – DNDi received a EUR 2 million strategic translation award from the Wellcome Trust to develop E1224
- 14 November 2013 – Drug trial for leading parasitic killer of the Americas shows mixed results but provides new evidence for improved therapy
- DNDi‘s Project of the Year 2013
Get our latest news, personal stories, research articles, and job opportunities.