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 15 Feb 2023
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’ main benefits were related to an improved safety profile, but further assessment was required to confirm non-inferiority compared to standard regimens. 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. In 2021, DNDi started a Phase III clinical trial in Argentina to validate a two-week regimen with benznidazole for adults in the chronic phase of the disease. In late 2021, recruitment was put on hold based on scientific evidence and new findings, including post-hoc analyses of the BENDITA study.
News & resources
- 14 April 2021 - Un medicamento en Fase II para la enfermedad de Chagas podría darse sólo dos semanas y ayudar a más pacientes, Infobae
- 7 April 2021 - Confirman la efectividad del tratamiento breve en la enfermedad de Chagas, Estrella digital
- 6 April 2021 - Chagas disease: Shorter treatment just as effective as longer one, according to study in Bolivia published by The Lancet
- 14 March 2019 - Study shows dramatically shorter treatment for Chagas disease could be just as effective, and significantly safer
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