2019 R&D portfolio in review: Sleeping sickness

 

DNDi aims to deliver new oral treatments to cure sleeping sickness that are safe, affordable, effective and easy to use, and that support the sustainable elimination of the disease.

 

Fexinidazole pill in a handDNDi’s current sleeping sickness portfolio includes:

 

R&D discovery stage iconDiscovery

 

  • SCYX-1330682 & SCYX-1608210: DNDcontinues to provide support and advice to researchers working on discovery of new candidates for HAT and maintains two back-up candidates from the oxaborole class to ensure future development options, if needed.

 

R&D development stage iconDevelopment

 

  • Acoziborole: The enrolment of 208 patients was completed in March 2019. The clinical study will be finished at the end of 2020 once 18-month post-treatment follow-up has been completed for all patients at clinical sites in the Democratic Republic of Congo and Guinea. In the interim, non-clinical studies to meet EMA and US FDA requirements will be carried out.

  • Fexinidazole: The last patients in the Phase IIIb trial whose purpose was to obtain additional clinical data on special populations (including pregnant and lactating women, and patients with poor nutritional status or chronic diseases) completed enrolment in August 2019. Post-treatment follow-up is anticipated to be completed by the end of 2020. A Phase IV access and pharmacovigilance study will begin in 2020.

    To assess fexinidazole to treat HAT caused by T.b rhodesiense – the other, more virulent subspecies of the parasite affecting humans – a Phase II/III study that aims to enrol 34 stage two patients began with enrolment of the first patient in Malawi in October 2019. A total of 20 patients were enrolled by February 2020.

    To provide clinical data to extend the indication to treat rhodesiense sleeping sickness with fexinidazole, we have joined with partners to form the HAT-r-ACC consortium with funding from the European & Developing Countries Clinical Trials Partnership. The consortium is working on a five-year project in Uganda and Malawi, which together account for 88% of rhodesiense sleeping sickness cases globally.

 

R&D implementation stage iconImplementation

 

  • Fexinidazole: Fexinidazole received a positive scientific opinion by the European Medicines Agency’s Committee for Medicinal Products for Human Use in November 2018 and was registered in the Democratic Republic of Congo in December 2018.

    Fexinidazole is now being donated by Sanofi to the World Health Organization (WHO) for distribution to national sleeping sickness control programmes in HAT-endemic countries. Fexinidazole distribution began in January 2020 in DRC. DNDi is supporting roll-out of fexinidazole and pharmacovigilance activities in DRC, Guinea, Central African Republic, Angola, and South Sudan to scale up access to this oral treatment for sleeping sickness caused by T.b. gambiense.

    WHO began training of trainers in 2019, first in DRC, followed by trainings in the HAT-endemic countries of Central and West Africa. DNDi will continue in-country training in collaboration with the HAT Platform, targeting relevant staff from 250 hospitals and health centres in T.b. gambiense-endemic countries.

  • Nifurtimox-eflornithine combination therapy (NECT): NECT was included on the WHO Essential Medicines List in 2009 and extended to the Essential Medicines List for Children in 2013. With the revision of WHO treatment guidelines for HAT in 2019 and the inclusion of fexinidazole, NECT will become the second-line treatment, though it remains the recommended first-line treatment in cases of advanced disease. Endemic countries will continue to receive free supplies from WHO via drug donations by Sanofi and Bayer.

 

Photo credit: Xavier Vahed-DNDi