Human African trypanosomiasis (HAT), also known as ‘sleeping sickness’, is transmitted by the tsetse fly. While currently its prevalence is declining, HAT is still a threat to millions of people across Sub-Saharan Africa with 83% (2013) of all cases in the Democratic Republic of Congo (DRC).

The WHO Roadmap (2012) to overcome the global impact of neglected tropical diseases (NTDs) has set the objective to eliminate HAT disease by 2020[1]. In support of this strategy, DNDi is carrying out an ambitious clinical development programme in close collaboration with NGO, research, and industrial partners, and national control programmes.

The current HAT portfolio includes:

Research

Two projects in the research phase:

Two backup candidates have been identified and are currently on hold in pre-clinical development in case SCYX-7158 (see project in clinical development) is precluded from further clinical development:

• SCYX-1608210 from the oxaborole class was identified and selected among a range of structurally diverse oxaboroles with good activity against T. brucei that were profiled in a laboratory pharmacokinetic (PK) study

• SCYX-2035811 is from the nitroimidazole class. The nitroimidazole backup programme for HAT has been searching for a compound with a lower projected human dose than fexinidazole to simplify dosing and mitigate any potential issues with tolerance.

Currently, two oral drug candidates that are both new chemical entities (NCEs) are in clinical development for HAT which, if successful, could become the first-ever oral-only treatments for the disease:

Translation

One project in the translation phase:

• A Phase I study with oxaborole SCYX-7158, will be completed by the end of this year. SCYX-7158, the first clinical candidate issued from the oxaboroles class provided by Anacor Pharmaceuticals and developed in partnership with SCYNEXIS, is also intended to treat stage 1 and 2 HAT. If successful, as a one-dose therapy (i.e. cure with one pill only), would provide significant advantages over NECT and even fexinidazole. It is expected to enter into a Phase II/III study in 2015.

Development

 One project in the development phase:

• A pivotal Phase II/III study with fexinidazole started in 2012 at nine clinical sites in the Democratic Republic of Congo and the Central African Republic[2]. Fexinidazole,the first success of the extensive compound mining efforts pursued by DNDi aimed to explore new and old nitroimidazole drug leads, would provide significant advantages over the current treatment standard NECT, which, while very effective, still requires hospital stays and specialized healthcare staff. A simple oral treatment, fexinidazole, if successful, will be easy to administer at the primary healthcare level and will allow patients to take their treatments home. The study has so far recruited 285 stage 2 HAT adult patients out of the 390 in total.. This year, following positive initial results of the trial, the study has also been extended both adult patients with stage 1 and early stage 2 of the disease, and in children between 6 and 14 years of age. Sanofi is DNDi’s industrial partner for this project.

If ultimately successful, fexinidazole and/or SCYX-7158 would be the first oral treatments to be used for both stage 1 and stage 2 sleeping sickness, thereby replacing the complicated diagnosis and treatment paradigm, which includes systematic lumbar punctures of every diagnosed patient to determine the stage of the disease before deciding which treatment to administer.

Implementation

 Implementation and access

DNDi continues to support the implementation and access to the Nifurtimox-Eflornithine combination treatment (NECT) that DNDi and its partners delivered in 2009. NECT has been included in the WHO Essential Medicines List since 2009 and is now on the Essential Medicines List for children (April 2013). Since June 2014, all countries endemic to T. b. gambiense are using NECT as first-line treatment for second stage HAT.

For more information on the partners and donors involved in DNDi HAT programme, please click on each hyperlink that will refer you to each project.