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 ideal goal is to develop two drugs that are effective against both stage 1 and 2 of HAT 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 hospitalization as treatment would no longer rely on administering a drug intravenously.
DNDi’s current HAT portfolio includes:
One project in the research phase:
- SCYX-1330682 and SCYX-1608210 oxaboroles: These two back-up candidates from the oxaborole class have demonstrated cure for stage 2 of the disease in the mouse model. Given the current success of other projects for HAT, further development was put on hold in 2013, and will only recommence should problems be encountered with SCYX-7158 in clinical development.
One project in the translation phase:
- SCYX-7158 oxaborole: 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. Seven study sites – Katanda, Isangi, Dipumba, Ngandajika, Masi Manimba, Kwamouth, and Bolobo – were initiated in Democratic Republic of Congo (DRC). Eleven patients (out of a target 350) had been recruited by the end of 2016.
One project in the development phase:
- Fexinidazole: In 2015, DNDi and the National HAT Control Programme (PNLTHA) of the DRC completed the recruitment of 394 adult patients with stage 2 HAT at ten clinical sites in the DRC and one (supported by MSF) in the Central African Republic, for the pivotal Phase II/III study which assesses the efficacy and safety of fexinidazole in comparison with nifurtimox-eflornithine combination therapy (NECT) in HAT stage 2 patients.
Two additional complementary cohorts with fexinidazole were also completed in 2016, one including 230 adult patients with stage 1 and early stage 2 of the disease, and another including 125 children between six and 14 years, both in DRC sites. Follow up of patients will be completed in 2017.
A Phase IIIb study aimed at getting more information about special population groups not included in previous fexinidazole trials (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 also providing 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 submission of a regulatory dossier to the European Medicines Agency under Article 58 is planned for the 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, and the study is planned to start in 2017.
Implementation and Access:
- NECT: Nifurtimox-Eflornithine Combination Therapy was included on the WHO Essential Medicines List in 2009, and extended to the List for children in 2013. With the recommendation of NECT as a first-line treatment in all endemic countries, all 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: Simon Tshiamala-DNDi