A two-week treatment with benznidazole for adults with chronic Chagas disease has similar efficacy and significantly fewer adverse effects than the current standard eight-week treatment, according to a study published by The Lancet Infectious Diseases.
These results are extracted from a Phase II clinical trial that was carried out in three centres in Bolivia, led by the Drugs for Neglected Diseases initiative (DNDi) and funded by the Global Health Innovative Technology Fund (GHIT).
The trial was carried out between 2016 and 2018, in cooperation with many partners around the globe, including the Bolivian CEADES (Science and Applied Studies Foundation for Health and Environment Development), the Barcelona Institute for Global Health (ISGlobal) –a centre supported by ”La Caixa” foundation-, the Japanese pharmaceutical company Eisai Co., Ltd. and the Argentinian pharmaceutical company Elea Phoenix S.A.
“A shorter treatment that is just as effective and much safer than the current one could be a game-changer for people with Chagas disease, who live for years with this debilitating disease,” said Faustino Torrico, principal coinvestigator of the trial and president of the CEADES foundation.
Chagas disease affects an estimated six million people globally and can cause irreversible, life-threatening damage to the heart and other vital organs if not treated. Current treatment with benznidazole, one of the two drugs used to treat the disease, is effective but has limitations: the treatment course lasts 60 days and around 20% of patients stop it due to serious side effects, which include gastric intolerance, skin rashes and neuromuscular problems.
“This was the first placebo-controlled study to compare different durations and doses of treatment with benznidazole, alone or in combination with fosravuconazole (E1224)," explained Joaquim Gascon, principal coinvestigator and director of the Chagas Initiative at ISGlobal.
The objective of the BENDITA (Benznidazole New Doses Improved Treatment & Therapeutic Associations) clinical trial was to find regimens that are at least as effective as the standard treatment while producing fewer side effects, in order to improve the patients’ adherence to treatment. Benznidazole was provided by Elea and fosravuconazole (E1224) was provided by Eisai Co., Ltd.
“This study provides hope for people affected by this neglected disease, as a shorter treatment will remove some concerns of caregivers and patients and will improve treatment adoption,” said Sergio Sosa Estani, Head of the Chagas Clinical Program at DNDi and researcher at CONICET (National Scientific and Technical Research Council) in Argentina.
Confirmatory studies with larger number of patients in Argentina and other countries will validate these findings before the new regimen can be adopted by Chagas patients. DNDi will soon launch a phase III clinical trialin Argentina in partnership with ELEA-Phoenix and Mundo Sano Foundation to confirm the efficacy and the safety of this 2-week regimen of benznidazole.
This upcoming study should also contribute to simplifying the treatment of young girls and woman of child-bearing age to prevent congenital transmission from previously treated mothers to their babies. As mothers can transmit Chagas disease to their children, the trial could help lead to the elimination of Chagas disease as a public health problem, which is one of the World Health Organization's Neglected Tropical Disease (NTD) Roadmap objectives for the next decade.
Reference: F Torrico, J Gascón, F Barreira, B Blum, IC Almeda, C AlonsoVega, T Barboza, G Bilbe, E Correia, W Garcia, L Ortiz, R Parrado, JC Ramirez, I Ribeiro, N Strub-Wourgaft, M Vaillant, S Sosa-Estani, on behalf of the BENDITA study group, New regimens of benznidazole monotherapy and in combination with fosravuconazole for Chagas disease (BENDITA): a phase 2, double-blind, randomised trial, Lancet Infect Dis 2021. https://doi.org/10.1016/S1473-3099(20)30844-6