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Human African Trypanosomiasis (HAT; sleeping sickness), is a parasitic disease caused by two related parasite strains, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. The HAT parasite is transmitted by the tsetse fly. Sleeping sickness is endemic to sub-Saharan Africa. It is characterized by two stages: an early hemolymphatic phase and a late encephalitic phase. If untreated, late-stage disease progresses to coma and death.

In the past century, sleeping sickness has killed millions of patients in Africa. Over the past two decades, coordinated global health efforts have reduced reported cases from more than 25,000 in 2000 to fewer than 600 in 2024. Disease vector control strategies such as “Tiny Traps” for tsetse flies and advances in treatment options have driven substantial progress, including the introduction of fexinidazole, the first all-oral treatment for sleeping sickness in 2018. However, other therapies for advanced Stage 2 disease can require complex administration and, in some cases, invasive lumbar punctures to determine disease stage and guide treatment decisions.

The development of acoziborole, a single-dose, oral curative treatment effective for both Stage 1 and Stage 2 HAT caused by the gambiense parasite, represented a significant opportunity to further simplify care and accelerate disease elimination. Developed through a collaboration between the Drugs for Neglected Diseases initiative (DNDi) and Sanofi, with funding support from the Gates Foundation, among other donors, acoziborole promised to transform the standard of care.

Challenge

Acoziborole has a pharmacokinetic profile that includes a long half-life. As part of the due diligence in preparation for the registration package, it was necessary to assess the drug-drug interaction potential and age-related metabolism.

解决方案

Certara global health experts have a track record of supporting the development of life saving medicines to treat neglected diseases including malaria, tuberculosis, and river blindness. With support from the Gates Foundation, Certara scientists worked strategically with DNDi and Sanofi to generate the evidence needed to support acoziborole’s approval. They used model-informed integrated drug development to analyze data and make recommendations to support the new drug application. Certara scientists provided state-of-the-art clinical pharmacology stewardship and physiologically-based pharmacokinetic (PBPK) modeling using its Simcyp® Simulator to minimize the number of clinical pharmacology studies required to adequately characterize acoziborole.

“The Certara team has expertise in guiding the development of therapies for addressing global health problems,” said Jean-Yves Gillon, Head of Translational Sciences, at the Drugs for Neglected Diseases initiative (DNDi). “I am thrilled that we were able to use this expertise to enable more efficient drug development which ultimately benefits patients.”

Impact

Acoziborole received a positive scientific opinion from the EMA through an accelerated assessment pathway designed to enable faster patient access to this medicine. This milestone positions the therapy for WHO prequalification and broader rollout across endemic regions.

The positive scientific opinion for acoziborole represents an important step forward in the fight against sleeping sickness. A safe and effective single-dose oral treatment has the potential to transform patient care and support ongoing efforts to eliminate this devastating disease.

结论

Acoziborole is currently indicated for treatment of adults and adolescents. Certara will continue this collaboration by providing input on the development of acoziborole for use in children.

The development of acoziborole demonstrates how model-informed drug development can accelerate therapies for neglected diseases. By combining scientific rigor, regulatory alignment, and a shared commitment to global health, this partnership illustrates how innovative development strategies can help deliver transformative therapies to the patients who need them most.

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