Special Edition 2021

NEW PRODUCTS

fexinidazole ( fexinidazole winthrop °) and sleeping sickness caused by Trypanosoma brucei gambiense Effective and more convenient than injectable treatments

A REAL ADVANCE Fexinidazole is the first drug for patients with trypanosomiasis caused by Trypanosoma brucei gambiense that can be taken orally and has high efficacy in both stages of the disease and acceptable adverse effects. Com­ pared with pentamidine and NECT ( nifurti- mox + eflornithine combination therapy), which require daily injections or infusions for 7 days, oral administration is a major advan­ tage for patients living in countries with limit­ ed health infrastructure, often in rural areas, and sometimes far from a healthcare facility. However, NECT remains the first choice for patients with the most advanced forms of the disease and who have access to this treat­ ment, as it is probably more effective in this situation. FEXINIDAZOLE WINTHROP° - fexinidazole tablets • 600 mg of fexinidazole per tablet ■ antiparasitic drug; 5-nitroimidazole derivative ■ Indication : “ first-stage (haemo-lymphatic) and second-­ stage (meningo-encephalitic) of human African tryp­ anosomiasis due toTrypanosoma brucei gambiense in adults and children ≥ 6 years old and weighing ≥ 20 kg ”. [Euro- pean Medicines Agency (EMA) evaluation procedure for drugs intended exclusively for use outside the European Union (Article 58 of European Regulation EC No 726/2004)] Human African trypanosomiasis (or sleeping sick- ness) is caused by a parasite of the genus Trypano- soma , usually T. brucei gambiense . The disease is endemic in many countries in sub-Saharan Africa, and is transmitted to humans through the bite of the tsetse fly (genus Glossina ), a haematophagous insect. It typically affects people living in rural or periurban areas. After an incubation period, sometimes lasting several years in the case of T. brucei gambiense , sleeping sickness progresses through two phases or stages: the haemolymphatic stage, followed by the more advanced meningoencephalitic stage. If left untreated, the disease is almost always fatal, within 2 to 3 years on average from the start of an infection caused by T. brucei gambiense (1,2).

The standard treatments for T. brucei gambiense infection are pentamidine during the haemolymph­ atic stage, and nifurtimox + eflornithine combination therapy (NECT) during the meningoencephalitic stage.These treatments are highly effective, with a cure rate of over 95%.They involve daily injections or infusions for 7 days (2).

What’s new?

An oral antiparasitic drug

Fexinidazole is a 5-nitroimidazole derivative, like metronidazole (3,4). Its mechanism of action in sleeping sickness is thought to involve conversion of the drug by parasite enzymes into metabolites that are toxic to trypanosomes. Nifurtimox is thought to have a similar mechanism of action (3). Fexinidazole (Fexinidazole Winthrop°, Sanofi Aventis) has been evaluated by the European Medi­ cines Agency (EMA) as a treatment for both stages of sleeping sickness due to T. brucei gambiense , in adults and children aged 6 years or more and weighing at least 20 kg. The evaluation was con- ducted through a European procedure for drugs intended exclusively for use outside the European Union (see also the inset “Development of fexini- dazole”, p. 289) (3,5). Is fexinidazole more effective than the standard treatments for sleeping sickness due to T. brucei gambiense ? Does it have fewer adverse effects? Is it easier to use? Fexinidazole has not been compared with penta­ midine in patients with haemolymphatic-stage human African trypanosomiasis due to T. brucei gambiense . Clinical evaluation of fexinidazole at this stage of the disease is based on two non-­ comparative trials (3,6). Fexinidazole was evaluated inmeningoencephalitic-­ stage disease in a randomised trial versus NECT (3,6,7). Full review (5 pages) available to subscribers at english.prescrire.org ▶ Translated from Rev Prescrire August 2020 Volume 40 N° 442 • Pages 565-567 Is it effective? Highly effective

Prescrire Int • December 2020

P age 4 • P rescrire I nternational S pecial E dition 2021