On 16 November the European Medicines Agency (EMA) approved a new drug, fexinidazole, for treating human African trypanosomiasis, known as sleeping sickness. The neglected tropical disease is endemic to Africa ― 78% of cases in 2017 were reported in the Democratic Republic of Congo (DRC), followed by the Central African Republic, Guinea, and Chad ― and caused by a parasite transmitted by the bite of the tsetse fly. The parasite can cross the blood-brain barrier entering the brain and causes horrendous symptoms including severe disruption in sleep patterns, aggressive behaviour, and psychosis. Without treatment, the disease is usually fatal.
According to Dr Victor Kandé, Neglected Tropical Diseases Expert Advisor to the Ministry of Health of the DRC, “Those affected are some of the most vulnerable and live in some of the most remote areas of the Congo, if not the world. They need a treatment that is safe, effective and simple.” Kandé who led the recent clinical trials involving 749 patients in the DRC and the Central African Republic has spent most of his career treating the illness.
Early treatments of sleeping sickness were based on an arsenic derivative that killed 5% of all patients. Newer treatments, including eflornithine and nifurtimox, are much safer but require patients to be hospitalized due to the complicated combination of infusions and pills. Patients must also undergo a painful procedure called a lumbar puncture ― fluid is taken from the spine through a hollow needle ― to determine whether the parasite is present. These requirements place a huge strain on health care systems and also make the costly treatment out of reach for many.
Fexinidazole is a 5-nitroimidazole derivative that can be taken orally as a pill once a day for 10 days. The drug was originally developed by Sanofi (formerly Hoechst), a global biopharmaceutical company, but abandoned in the 1980s for strategic reasons. In 2005, fexinidazole was rediscovered by the Swiss Tropical and Public Health Institute and Drugs for Neglected Diseases initiative (DNDi) ― a non-profit R&D organization working on new treatments for neglected diseases ― as part of a collaboration to uncover compounds with anti-parasitic activity.
Sanofi and DNDi worked together to test the drug in patients to prove its efficacy and then, to apply for the EMA recommendation under Article 58, a special set of rules designed to help new drugs reach the market in low- and middle-income countries outside of the European Union. The recent approval was based on recommendations given by experts from the EMA, WHO, and affected nations. The fexinidazole programme cost €55 million was supported by seven European countries (France, Germany, the Netherlands, Norway, Spain, Switzerland and the UK) as well as private donors including the Bill & Melinda Gates Foundation and Médecins Sans Frontières.
The EMA’s “positive opinion” has paved the way for approval in individual countries within 90 days and fexinidazole should be available by mid-2019. This is a huge win for DNDi and Sanofi, as well as the many African people affected by the horrific disease. Fexinidazole is the “first new chemical entity to be developed by DNDi,” according to Dr Bernard Pécoul, Executive Director of DNDi, and was “developed through an alternative non-profit R&D model.” Chief Medical Officer and Executive Vice President Medical Function of Sanofi Dr Ameet Nathwani says, “Fexinidazole is the proof that partnerships between public and private sectors can deliver safe and effective medicines for the most neglected patients.”
It is hoped the new powerful drug will improve the lives of thousands of patients in West and Central Africa.
Image credit: Xavier Vahed/DNDi