references
HUMAN AFRICAN TRYPANOSOMIASIS / SLEEPING SICKNESS
R&D MODEL & PORTFOLIO
DEVELOPMENT
Fexinidazole
PROJECT START: April 2007 OVERALL OBJECTIVE: Develop and register fexinidazole as a new oral drug for the treatment of HAT caused by T. b. gambiense (g-HAT), ideally also to be used for T. b. rhodesiense (r-HAT) 2015 OBJECTIVES:
regimen with doses adapted to children’s weight. In total therefore, information collected from 749 individuals will be included in the safety database. More information from special population groups not included in trials to date, such as pregnant and breastfeeding women, patients with poor nutritional status or with chronic diseases, will be obtained in a planned Phase IIIb trial. This will also include a cohort of outpatients and will provide preliminary information about treatment compliance and use on an outpatient basis. 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 commence in 2017. The submission of a regulatory dossier to the European Medicines Agency (EMA) under Article 58 is planned for 2017, for the treatment of g-HAT with fexinidazole. This provision allows the EMA’s Committee for Medicinal Products for Human Use (CHMP) to give scientific opinions, in co-operation with the World Health Organization (WHO), on drugs to prevent or treat diseases of major public health interest and intended exclusively for markets outside the European Union. It aims to ensure faster WHO prequalification of medicines by removing barriers to simultaneous prequalification. A Risk Management Plan to further monitor safety and efficacy in the field is under preparation in collaboration with Sanofi and WHO.
PARTNERS: Sanofi, France; Swiss Tropical and Public Health
• Complete recruitment of the pivotal Phase II/III study of fexinidazole versus the reference treatment (NECT) • Complete recruitment of the studies in adults with stage 1/early stage 2 g-HAT and in children above 6 years of age and over 20 kg weight (both stages)
Fexinidazole, the result of successful compound-mining efforts pursued recruited at 10 sites by DNDi in 2005, entered clinical development in September 2009 and is being co-developed with Sanofi: DNDi is undertaking clinical and pharmaceutical development whilst Sanofi is responsible for the industrial development and production. Fexinidazole is the most advanced oral candidate under development for HAT. DNDi aims to evaluate and register it as a treatment for a wide range of patients, specifically in adults and children over 6 years of age and 20 kg body weight with either stage of disease. The pivotal study compares fexinidazole in patients with late stage g-HAT versus NECT, and completed inclusions of all 394 patients between October 2012 and April 2015. The 18 month follow-up period will end in 2016, and results processed for regulatory submission in Q3 2017. Additional safety and efficacy data from the two complementary studies will also be included; the first reached 230 early stage adult patients and the second 125 children aged 6-14 years (approximately equal numbers of early stage and late stage patients) in an open, non-comparative study, using the same
749 patients
Institute (Swiss TPH), Switzerland; Institute of Tropical Medicine (ITM) – Antwerp, Belgium; Médecins Sans Frontières; Institut de Recherche pour le Développement (IRD), France; Institut National de Recherche Biomédicale (INRB), DRC; HAT Platform; National Control Programmes of the Democratic Republic of Congo and the Central African Republic.
IMPLEMENTATION
NECT: Nifurtimox-Eflornithine Combination Therapy
PROJECT START: May 2004 OVERALL OBJECTIVE: Develop and make available a safe, effective, easier to administer and more cost-effective combination therapy which requires shorter hospitalization 2015 OBJECTIVE: Prepare the field for change of policy and
implementation
365 NECT kits distributed, sufficient to treat 1,460 patients
