R&D Portfolio Update February 2019: DNDi Sleeping sickness programme

 

DNDi aims:

  • To complete the development and register 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).

 

Lab technicians looking into microscope in a clinical working on sleeping sicknessDNDi’s current human African trypanosomiasis (HAT) portfolio includes:

 

Research

Discovery

Work in the discovery 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 Development

One project in the development phase:

 

  • Acoziborole: Phase I trials of 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 2018, recruitment of patients continued with 191 patients enrolled to date, including 148 late stage-2 patients. Three new clinical sites in Democratic Republic of Congo (DRC) – Nkara, Kimpese, and Bagata – were added to the already active sites (Katanda, Isangi, Roi Baudouin Hospital in Kinshasa, Dipumba, N’gandajika, Masi Manimba, Kwamouth, Bandundu). A new site also opened in Guinea (Dubreka).

  • 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.

    A Phase IIIb trial that started in 2016 is ongoing, with 116 patients (of a target 174) recruited in this study 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). 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 (Bandundu, Bagata, Mushie, Masi Manimba, Dipumba, Roi Baudouin Hospital, Kinshasa).

    A new Phase II/III study is also 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.

 

Implementation

Implementation

Implementation and access:

 
  • Fexinidazole will be donated by Sanofi to the World Health Organization for distribution to national sleeping sickness control programmes in endemic countries. Fexinidazole was registered in the Democratic Republic of Congo in December 2018, and patients should have access the drug in the coming months. Access to fexinidazole in other endemic countries will follow.
  • 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 stage-2 HAT patients are now treated with NECT.
 
 

Photo credit: Xavier Vahed-DNDi