Trial renews interest in Chagas' disease

Abstract

Chagas' disease is receiving more international attention as news emerged that the first trial in 40 years of a drug for the condition is to begin next year. Anastasia Moloney reports. After a void of medical research on Chagas' disease for decades, campaigners hope that the trial of a new drug will lead to the development of a better treatment for the neglected condition. Chagas' disease, transmitted by the parasite Trypanosoma cruzi, a blood-sucking bug endemic to Latin America, affects an estimated 8 million people worldwide and kills more people in the region each year than any other parasite-borne disease, including malaria. Around 14 000 people worldwide, often from poor, rural communities in South America, die from the tropical disease each year. Current drugs being used to treat the disease produce side-effects such as nausea, skin rashes, skin inflammations associated with swollen or enlarged lymph nodes, and abdominal pain. The non-profit drug research and development organisation, Drugs for Neglected Disease Initiative (DNDi), is teaming up with Eisai, a Japanese pharmaceutical company, to test the safety and effectiveness of a prodrug of the antifungal ravuconazole in patients with Chagas' disease. The trial, the first in 40 years of a new drug for this disease, is planned to start late next year in South America. Under the licence agreement announced last month, the Swiss-based DNDi will be solely responsible for the clinical trials. “This is the first clinical trial in a long time using a new class of compounds with a potential use for Chagas' disease. We do not know whether it will work but just to be able to go ahead and test its potential is good news”, said Isabela Ribeiro, DNDi's senior project manager in Brazil. Ravuconazole, discovered and produced by Eisai, is one of a new generation of antifungal drugs. In-vitro and in-vivo studies have shown that ravuconazole has potent effects against the pathogen responsible for Chagas' disease. Researchers are pinning hopes on the drug's special properties that could lead to improved treatment of Chagas' disease, particularly during the chronic phase of the disease in adults, when current drugs being used have little efficacy. “Ravuconazole…stays very long in the blood and distributes well into tissues. These properties seem to have great potential for the treatment of Chagas”, explained Ribeiro, who will be overseeing the clinical trials. Ravuconazole, a prodrug that is broken down and transformed when absorbed into the bloodstream, is active in the body for longer than benznidazole and nifurtimox, the only two antiparasitic drugs being used to treat Chagas' disease. This means ravuconazole could be potentially taken by patients less frequently. Benznidazole and nifurtimox are taken in two or three doses per day for up to 90 days, making it difficult for patients to complete the long course. “We've been using the same two drugs since the 1960s”, said Ribeiro. “They have limitations and cause a high incidence of side-effects in adults.” It is likely that phase 1 clinical trials will take place exclusively in Bolivia, which has the highest rate of Chagas' disease in the world, and involve around 400 patients, said Ribeiro. Initially trials will focus just on adults with chronic and indeterminate Chagas' disease. This is the population most in need and with the greatest burden of the disease. The idea is to target this population before they develop organ problems. About 30% of people living with Chagas' disease will develop life-threatening health problems, most commonly heart failure and intestinal complications. Clinical trials are being planned to produce a paediatric tablet of benznidazole. Neither benznidazole nor nifurtimox is currently available in a paediatric formulation. Children are being treated with adult medication, broken up into as many as 12 pieces, depending on the child's body weight, making it difficult to ensure a correct dosage. As more cases of Chagas' disease are being diagnosed across the world, it is likely that research will be stepped up and greater efforts made to improve diagnosis and treatment of the neglected disease. “There's growing concern about Chagas”, said Ribeiro. Worldwide migration has led to the spread of the disease outside of Latin America. 300 000 people live with Chagas' disease in the USA, and more cases are being reported in Europe, Australia, and Japan.