New single-dose oral treatment for human African trypanosomiasis (sleeping sickness)

Acoziborole Winthrop simplifies treatment of first- and second-stage disease caused by T. brucei gambiense
NewsHumanMedicines for use outside the EU

EMA’s human medicines committee (CHMP) has adopted a positive scientific opinion for Acoziborole Winthrop for the treatment of human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense (g-HAT).

Acoziborole Winthrop is intended for use outside the European Union (EU) and was assessed under the EU-M4all programme. EU-M4all aims to facilitate patient access in low- and middle-income countries to essential medicines intended to prevent or treat diseases of major public health interest.

g-HAT occurs in some parts of Africa and is classified as a neglected tropical disease by the World Health Organization (WHO). Following concerted efforts to control g-HAT, transmission has been eliminated in many countries. Fewer than 1,000 cases arenow reported annually on the African continent. However, the disease is usually fatal without treatment and current therapies are complex.

g-HAT is spread through the bite of tsetse flies infected with the parasite Trypanosoma brucei gambiense. In the first few days after infection, patients may have symptoms such as fever, headache and rash (first stage). Later, they may experience a more severe form of the disease which affects the nervous system, causing symptoms such as sleep disturbances and changes in behaviour (second stage).

Acoziborole Winthrop is indicated for use in adults and adolescents from 12 years of age weighing at least 40 kg to treat first-stage and second-stage (including severe second-stage) g-HAT.

The exact way that Acoziborole Winthrop works is not fully understood. However, data suggest that its active substance, acoziborole, binds to and blocks the activity of an enzyme that the parasite needs to produce essential proteins, causing the parasite to die.

Current therapies for g-HAT involve multiple doses, intravenous infusions or intramuscular injections, as well as hospitalisation. They are selected based on disease stage, which is determined by a lumbar puncture (spinal tap). Acoziborole Winthrop is given as a single oral dose and is effective in all stages of g-HAT, removing the need for lumbar puncture and hospitalisation. This simplifies treatment for patients, facilitating compliance and accessibility.

The safety and efficacy of Acoziborole Winthrop are based on the results of a single-arm open-label phase II/III clinical trial carried out in the Democratic Republic of Congo and Guinea. The study involved 208 adults and adolescents from 15 years of age with g-HAT who received a single dose of the medicine.

The results showed that, after 18 months, treatment was successful in around 95% (159 out of 167) of people with second-stage disease and in 100% (41 out of 41) of people with first- and intermediate‑stage g-HAT. Treatment success was based on the absence of clinical signs of g-HAT, no detectable parasites and a white blood cell count below a set limit. Supportive data also showed that in adolescents aged 12 to 17 and weighing at least 40 kg the medicine is expected to behave in the same way as in adults.

The most common side effects reported with Acoziborole Winthrop were headache, fever, weakness, decreased appetite and tremor. The medicine is not for use in people with pre-existing heart rhythm problems, nor should it be taken with certain medicines used to treat HIV and some other infections. Patients will receive a card to explain these risks. The company will also perform a post‑authorisation study to collect information on the real-world safety of the medicine during the 3 months after treatment.

EMA’s positive scientific opinion will streamline the WHO prequalification and facilitate national registration of Acoziborole Winthrop for use in public health programmes in countries where the disease is endemic. The application for scientific opinion was assessed under an accelerated timetable to enable faster patient access to this medicine.

Medicines submitted under the EU-M4all programme are assessed by the CHMP in collaboration with the WHO and the target countries, combining EMA’s scientific review capabilities with the epidemiology and local disease expertise of WHO and experts and national regulators in the target countries. 

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