Evaluate new therapeutic regimens of benznidazole as monotherapy, or in combination with fosravuconazole, for the treatment of adult patients with chronic Chagas disease.
current phase of drug development
updated 1 Mar 2022
Benznidazole, currently the standard treatment for Chagas disease, is effective but has limitations: the treatment lasts 60 days, and some 20% of patients stop treatment due to side effects, which can include gastric intolerance, skin rashes, and neuromuscular problems. To explore whether the side effects were related to dose or treatment duration, DNDi decided to test the efficacy of new regimens where exposure to benznidazole would be reduced, either due to shorter treatment, lower doses, or both.
In 2013, a proof-of-concept trial showed that fosravuconazole, an azole-class antifungal drug discovered by Eisai Ltd (Japan), had good safety and was effective at clearing the parasite, but efficacy was not sustained. A Phase I drug-drug interaction study assessed the safety and pharmacokinetic interactions of fosravuconazole and benznidazole administered separately and in combination. No major clinically relevant safety or tolerability issues were identified.
The BENDITA (Benznidazole New Doses Improved Treatment & Therapeutic Associations) study looked for regimens at least as effective as the standard treatment, with fewer side effects. From 2016 to 2018, a Phase II, randomized, placebo-controlled study was carried out in three sites in Bolivia to test six benznidazole treatments of differing lengths and dosages, both as a monotherapy and in combination with fosravuconazole, against a placebo. The aim was to improve efficacy, safety, and tolerability of treatment of adults with chronic indeterminate Chagas disease, thereby improving patients’ adherence and making the treatment more acceptable to physicians.
Results showed that the new regimens presented good safety profiles. DNDi continues to work with national programmes, partners, and health ministries of endemic countries to confirm these results and encourage the necessary steps to register the new regimen. Currently, DNDi is conducting a Phase III clinical trial in Argentina to validate a two-week regimen with benznidazole for adults in the chronic phase of the disease.
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