A two-week treatment with the antiparasitic drug 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).
‘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 Dr Faustino Torrico, co-principal investigator of the trial and President of the CEADES Foundation.
The trial was carried out between 2016 and 2018, in cooperation with many partners around the globe, including the Bolivian non-profit CEADES (Science and Applied Studies Foundation for Health and Environment Development), the Barcelona Institute for Global Health (ISGlobal), a centre supported by the ”La Caixa” Foundation, the Japanese pharmaceutical company Eisai Co., Ltd., and the Argentinian pharmaceutical company Elea.
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),’ said Joaquim Gascon, co-principal investigator and Director of the Chagas Initiative at ISGlobal.
Benznidazole was provided by Elea and fosravuconazole (E1224) was provided by Eisai Co., Ltd.
‘Although we could not verify the efficacy of the combination treatment of benznidazole and fosravuconazole (E1224) compared to treatment with benznidazole alone, the study confirmed the new regimen, with fewer adverse effects, which has potential to be a new standard treatment. We are pleased to have contributed to the creation of this evidence. Based on our human health care (hhc) corporate philosophy, we will continue to work with public and private partners including DNDi for the elimination of NTDs,’ said Dr Kappei Tsukahara, Vice President, Chief Data Officer and Head of Tsukuba Research Laboratories at Eisai Co., Ltd.
The objective of the BENDITA (Benznidazole New Doses Improved Treatment & Therapeutic Associations) clinical trial was to find regimens that are as effective as the standard treatment while producing fewer side effects to improve patient adherence to treatment. ‘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 Programme at DNDi and researcher at CONICET (National Scientific and Technical Research Council) in Argentina.
Confirmatory studies with a 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 trial in Argentina in partnership with ELEA-Phoenix and Mundo Sano Foundation to confirm the efficacy and the safety of this two-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.
‘This is truly a remarkable achievement made possible by international collaboration. With this new finding, we opened up a new way to provide a new shorter regimen for patients. We appreciate patients, their families, healthcare professionals, and all the partners who joined the BENDITA study. We also thank Eisai for providing their drug fosravuconazole (E1224) for the combination treatment arms in the clinical trial to compare efficacy and safety,’ said Ms. Catherine Ohura, the CEO and Executive Director of GHIT.
For this study, DNDi received financial support from the Global Health Innovative Technology Fund, Japan; the UK Department for International Development (UK Aid); the German Federal Ministry of Education and Research through KfW; the Dutch Ministry of Foreign Affairs; the Brazilian Ministry of Health; the Associação Bem-Te-Vi Diversidade, Brazil; the Fundação Oswaldo Cruz (Fiocruz), Brazil; and the Starr International Foundation, Switzerland.
For its overall mission, DNDi also receives funding from the Swiss Agency for Development and Cooperation, Switzerland and Médecins Sans Frontières International. Non-conventional serology assays were performed at the Biomolecule Analysis Core Facility (currently, Biomolecule Analysis and Omics Unit) at the Border Biomedical Research Center, University of Texas at El Paso, funded by the National Institute on Minority Health and Health Disparities.
A not-for-profit research and development organization, DNDi works to deliver new treatments for neglected patients, those living with Chagas disease, sleeping sickness (human African trypanosomiasis), leishmaniasis, filarial infections, mycetoma, paediatric HIV, and hepatitis C. DNDi is also coordinating a clinical trial to find treatments for mild-to-moderate COVID-19 cases in Africa. Since its inception in 2003, DNDi has delivered eight new treatments to date, including new drug combinations for kala-azar, two fixed-dose antimalarials, and DNDi’s first successfully developed new chemical entity, fexinidazole, approved in 2018 for the treatment of both stages of sleeping sickness. dndi.org
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