DNDi aims to deliver:
- A safe, effective, and orally administered drug to replace current first-line HAT treatments, and to improve and simplify current case management.
- The goal is to develop two drugs that are effective against both stages of the disease and both subspecies of the parasite (Trypanosoma brucei gambiense (g-HAT) and Trypanosoma brucei rhodesiense (r-HAT)).
- If successful, this would represent a fundamental shift in disease management, as it would remove the need both for a risky and painful lumbar puncture test to confirm the disease stage, and for systematic hospitalization, as treatment would no longer rely on administering a drug intravenously.
DNDi’s current HAT portfolio includes:
Research
Work in the research phase:
- DNDi continues 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.
Development
Two projects in the development phase:
- Acoziborole (SCYX-7158): Phase I trials on this new chemical entity were completed in 2015, and allowed the therapeutic dose to be determined at 960mg, administered as a single dose of three tablets. A pivotal Phase II/III trial started in the last quarter of 2016. In 2017, recruitment continued with the inclusion of 76 patients (out of 210 patients in total) in eight clinical sites in DR Congo, including two new sites in Bandundu and Roi Baudoin Hospital (Katanda, Isangi, Dipumba, N’gandajika, Masi Manimba, Kwamouth, Bandundu, and Roi Baudoin Hospital in Kinshasa). One site (Bolobo) was closed in December 2017. Three more sites are planned to open in 2018, including one in Guinea.
- Fexinidazole: 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 lumbar puncture and systematic patient hospitalization. A regulatory dossier was submitted to the European Medicines Agency under Article 58 for the treatment of Trypanosoma brucei gambiense HAT (stages 1 and 2). Results were presented at ECTMIH in October 2017 and published in The Lancet.
A Phase IIIb trial to obtain more information about special populations not included in previous fexinidazole trials (including pregnant and lactating women, and patients with poor nutritional status or chronic diseases) started in 2016 and is ongoing. Patients are treated either in hospital, or at home, thereby also providing preliminary information about treatment compliance and final effectiveness in ambulatory patients.
Recruitment continued in the Phase IIIb study with the inclusion of 45 patients (out of 174 in total) in five sites (Bandundu, Bagata, and Mushie, Masi Manimba, and Dipumba). Masi Manimba was opened in June 2017 and Dipumba in October 2017. An additional new site (Roi Baudouin Hospital, Kinshasa) was initiated in December and started recruitment in January 2018. 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 disease, and another including 125 children between 6 and 14 years, both at sites in DR Congo. Follow-up of patients was completed in 2017.
In 2015, DNDi and the National HAT Control Programme (PNLTHA) of DR Congo completed the recruitment of 394 adult patients with stage 2 sleeping sickness at ten clinical sites in DR Congo and one supported by MSF in the Central African Republic, for a pivotal Phase II/III study to assess the efficacy and safety of fexinidazole in comparison with nifurtimox-eflornithine combination therapy (NECT) in stage 2 patients.
Implementation
Implementation and Access:
- NECT: Nifurtimox-eflornithine combination therapy (NECT) was included on the WHO Essential Medicines List in 2009 and extended to the Essential Medicines List for Children in 2013. With the recommendation of NECT as first-line treatment in all endemic countries, all of which receive free supplies from WHO via drug donations by Sanofi and Bayer, 100% of HAT stage 2 patients are now treated with NECT.
Photo credit: Neil Brandvold-DNDI
