Access activities were consolidated in 2023 following completion of the clinical development of fexinidazole for T.b. gambiense sleeping sickness in 2022. All endemic countries are utilizing fexinidazole as a first-line treatment, health staff have been trained on the new treatment guidelines, and pharmacovigilance is ongoing in five countries (Democratic Republic of the Congo, Central African Republic, Guinea, Angola, and South Sudan). Community awareness activities were carried out in the most endemic areas of the Democratic Republic of the Congo using communication materials updated based on recommendations emerging from an ethnographic study implemented by DNDi and partners.

The clinical development of fexinidazole for T.b. gambiense sleeping sickness was completed with the finalization of the last clinical study report, which is expected to be published in 2023. Access activities continued throughout the year, including in additional countries where fexinidazole has been adopted as the first-line treatment for sleeping sickness caused by T.b. gambiense. The post-approval safety study will be finalized in the second quarter of 2023. Training on the new treatment guidelines was completed and the team is now concentrating on improving routine pharmacovigilance reporting using fexinidazole as an example in five countries (Democratic Republic of the Congo, Central African Republic, Guinea, Angola, and South Sudan). The ethnographic study was completed and published.

In July 2021, DNDi and Sanofi registered fexinidazole with the US Federal Drug Administration, obtaining the rights for a priority review voucher. Access activities launched in 2020 continued and will run until at least 2024. These activities include extending diagnosis and treatment coverage in the health system through the rehabilitation, construction, and equipping of health centres and training of health staff; supporting safety follow-up within the Sanofi post-approval safety study; reinforcing national pharmacovigilance systems in five of the most endemic countries to guarantee sustainable safety reporting; and conducting ethnographic research to inform and reinforce community awareness and develop new communication tools and campaigns.

Fexinidazole distribution began in January 2020 in the Democratic Republic of Congo. DNDi continued to support the roll-out of fexinidazole, including active support for access and pharmacovigilance activities, in Angola, Central African Republic, the Democratic Republic of Congo, Guinea, and South Sudan. In September 2020, DNDi received funding through the Democratic Republic of Congo’s Health System Strengthening for Better Maternal and Child Health Results (PDSS) project to continue in-country training, in collaboration with the HAT Platform, for relevant staff from 250 hospitals and health centres in countries where T.b. gambiense is endemic.

Patient follow-up for DNDi’s Phase IIIb trial to obtain clinical data on special populations concluded in February 2021; however, the COVID-19 pandemic caused monitoring visits in Guinea to be put on hold. Study results are expected in late 2021.

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.

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 project will begin in 2020.

Fexinidazole received a positive scientific opinion by the 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.

A Phase IIIb trial that started in 2016 is still ongoing, with 116 patients (of a target 174) recruited. Patients are treated either in hospital, or at home, thereby also providing preliminary information about treatment adherence and final effectiveness in ambulatory patients. In 2018, two new clinical sites in DRC (Nkara and Kimpese) and one in Guinea (Dubreka) were added to the already active sites.

In addition, a Phase IV study to support access to fexinidazole and collect pharmacovigilance data is also under preparation. The first patients are expected to be enrolled by the end of 2019.

Lastly, a Phase II/III study is being prepared in Malawi to assess fexinidazole to treat HAT caused by T.b rhodesiense, the other subspecies of the parasite that causes sleeping sickness, and one that causes a more virulent strain of the disease occurring primarily in East and Southern Africa. Protocols have been submitted and the study should start in mid-2019.

Phase II/III study results published in 2017 confirmed that fexinidazole is safe and effective, and presents significant advantages over NECT, as it removes both the need for a systematic lumbar puncture and patient hospitalization. A regulatory dossier was submitted to the European Medicines Agency under Article 58 for the treatment of T.b. gambiense HAT (stages 1 and 2). Results were presented at ECTMIH in October 2017 and published in The Lancet.

The Phase IIIb trial that started in 2016 to obtain more information about special populations not included in previous fexinidazole trials is ongoing. Recruitment continued in 2017 with the inclusion of 45 patients (out of 174 in total) in five sites (Bandundu, Bagata, and Mushie, Masi Manimba, and Dipumba). Three more sites are planned to be opened in 2018, including one in Guinea.

Two additional complementary cohorts with fexinidazole were completed in 2016, one including 230 adult patients with stage 1 and early stage 2 of the disease, and another including 125 children between 6 and 14 years, both in DRC sites. Follow up of patients will be completed in 2017.

A Phase IIIb aiming at getting more information about special population groups not included in previous fexinidazole trials (including pregnant or lactating women, and patients with poor nutritional status or with chronic diseases) started in 2016. Patients will be treated either in hospital, or at home, thereby providing also preliminary information about the treatment compliance and final effectiveness in ambulatory patients. Three sites were initiated (Bandudu, Mushie and Bagata) and six patients (out of a target of 174) had been recruited by the end of 2016.

The results of the Phase II/III study support the submission of a regulatory dossier to the European Medicines Agency under Article 58, planned for late 2017 for the treatment of g-HAT with fexinidazole. It aims to facilitate faster WHO prequalification of the medicine as well as regulatory approvals and implementation in endemic countries. A risk management plan to further monitor safety and efficacy in the field is under preparation in collaboration with Sanofi and WHO.

In addition, the protocol for a study to be undertaken in r-HAT patients is being finalized, sites in Uganda and Malawi have been identified.

The pivotal Phase II/III study with fexinidazole completed this year, the recruitment of 394 stage 2 HAT patients at ten clinical sites in the Democratic Republic of Congo and the Central African Republic. A second study in adult patients with stage 1 and early stage 2 of the disease that was initiated in 2014 has recruited 228 patients to date. A third study in children between six and 14 years, also initiated in 2014, has recruited 125 patients to date.