R&D status November 2015: DNDi Chagas disease programme

[November 2015]

The parasite that causes Chagas disease is transmitted by the ‘kissing bug’ and also by blood transfusion, organ transplantation, and congenitally. The disease is endemic in 21 countries in Latin America, where 70 million people are at risk.

An estimated 6 million people are infected in the region, and patient numbers are growing in non-endemic, high-income countries as well. Though currently available treatments (benznidazole and nifurtimox) show good efficacy, they still present drawbacks, including long treatment periods and side-effects. Today, it is estimated that less than 1% of those affected are treated.

DNDi’s current Chagas disease portfolio includes:


Research
Research


One project in the research phase:

  • Chagas H2L (hit-to-lead): The project evaluates hits identified from screening and begins the process of optimizing new chemical series. If promising activity can be demonstrated in in vivo models of Chagas disease then the series will be advanced into full lead optimization programmes. This process of hit-to-lead optimization is ongoing with multiple series from several pharmaceutical companies.

 

Translation
Translation

Three projects are in the translation phase:

  • New Benznidazole Regimens/Combinations: From 2011 to 2013, DNDi and partners conducted a proof–of-concept study assessing three different regimens of fosravuconazole, a new drug candidate from the azole-compound class, on the one hand, and benznidazole, on the other hand, in a double-blind placebo controlled trial. This study prospectively confirmed the efficacy of benznidazole in chronic indeterminate Chagas disease but failed to show sustained efficacy for any regimen of fosravuconazole. To optimize benznidazole regimens in combination with fosravuconazole, a drug-drug interaction (DDI) study was conducted to demonstrate the safety of administering both drugs together. The study was undertaken in Buenos Aires, Argentina. Twenty-eight healthy human volunteers were recruited and the trial concluded with no major clinically relevant safety or tolerability issues identified. Following this DDI study, DNDi is undertaking preparatory activities for a proof-of-concept study that will assess simultaneously selected benznidazole new doses and durations in monotherapy and benznidazole/fosravuconazole combination regimens. The study will take place in Argentina and Bolivia and will include approximately 200 patients.
  • Fexinidazole: A Phase II proof-of-concept study of the New Chemical Entity (NCE) fexinidazole started in 2014 in Cochabamba and Tarija, Bolivia. A total of 180 patients were selected for study participation and 47 were included. The study was interrupted due to safety and tolerability issues.
  • Biomarkers: Pre-clinical studies are ongoing to identify and validate potential markers of therapeutic response in Chagas disease patients to support clinical development.

Implementation
Implementation

 

Implementation and access to treatments:

Together with the Global Chagas Coalition and other key stakeholders, DNDi is actively supporting endemic countries to develop policies and mechanisms to scale up diagnosis and treatment of Chagas disease patients with existing therapies. Five pilot regions have been identified to implement operational studies and assessments of new models of intervention in partnership with National Control Programmes.

 

From its Chagas disease-specific portfolio, DNDi aims to develop:

  • A new benznidazole monotherapy regimen for chronic Chagas disease patients
  • A new benznidazole and fosravuconazole combination treatment regimen for chronic Chagas disease patients

 

 

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