EMA Panel Backs First Oral-Only Drug for Deadly Sleeping Sickness

Megan Brooks


November 16, 2018

The first oral-only treatment for human African trypanosomiasis (HAT), commonly known as sleeping sickness, has received a green light from the Committee for Human Medicinal Products (CHMP) of the European Medicines Agency (EMA).

Fexinidazole Winthrop (fexinidazole, 600 mg tablets) is indicated as a 10-day once-a-day treatment for both the first-stage (hemolymphatic) and second-stage (meningo-encephalitic) of HAT caused by Trypanosoma brucei gambiense in adults and children aged 6 years and older who weigh at least 20 kg.

Fexinidazole was developed by Sanofi-Aventis in partnership with the Drugs for Neglected Diseases initiative (DNDi), a nonprofit drug research and development organization based in Switzerland. Fexinidazole is intended exclusively for markets outside the European Union.

HAT is a life-threatening, neglected tropical disease endemic to sub-Saharan Africa. It is caused by two subspecies of the flagellate protozoan Trypanosoma brucei: Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. The organisms are transmitted by bites of infected tsetse flies.

The vast majority of cases of HAT (98%) are caused by T brucei gambiense and occur in the Democratic Republic of the Congo (DRC). The remainder occur in central African countries that border the DRC.

This is a huge leap in how we can tackle this deadly disease. Dr Victor Kande

HAT caused by T brucei gambiense is characterized by "a more chronic disease evolution," the EMA explains in a news release. Within weeks of infection, patients can experience fever, headaches, joint and muscle pains, and itching.

Over time, the disease invades the central nervous system (CNS). Patients often develop mental confusion, slurred speech, seizures, difficulty walking and talking, and worsening sleep problems. If left untreated, HAT is typically fatal within 2 to 3 years.

Current treatments include intramuscular injections of pentamidine, which are only effective in the earlier stage of the disease. Other treatments include a combination of oral nifurtimox and intravenous infusion of eflornithine when the disease has advanced and affects the CNS. However, these treatments require a minimum health infrastructure and personnel, which are not readily available in some remote areas, the EMA notes.

As an all-oral treatment, fexinidazole "could potentially allow quicker and wider access to treatment because distribution and administration of tablets is easier," the EMA said.

"Fexinidazole comes as a simple pill: this is a huge leap in how we can tackle this deadly disease," added Victor Kande, MD, expert advisor to the Ministry of Health of the DRC regarding neglected tropical diseases, in a press release. Dr Kande was the principal investigator for the trials.

Fexinidazole was evaluated in three clinical studies that involved 749 patients with different stages of the disease. The studies showed high cure rates in patients after 10 days of treatment, especially in the earlier stage of the disease. For patients with marked CNS involvement, fexinidazole "should only be given under strict supervision in hospital when no other adequate treatment is available or tolerated," the EMA said.

The most common side effects with fexinidazole are vomiting, nausea, headache, insomnia, weakness, dizziness, and tremor.

Because a small number of cases of late relapse occurred in clinical testing, the CHMP recommends follow-up monitoring of up to 24 months to detect potential relapses.

This is the tenth medicine recommended by the EMA under Article 58, a regulation that allows the CHMP to assess and give opinions on medicines that are intended for use in countries outside the European Union.

"The scientific opinion from the CHMP helps to support regulators in countries where regulatory capacity may be limited, by providing an expert evaluation of the medicine when used in local practice. National regulators can use the CHMP's scientific assessment to decide on the use of the medicine in their countries," the EMA explains.

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