R&D status September 2014: DNDi Chagas disease programme

[September 2014]

Chagas disease is transmitted by the ‘kissing bug’ and also by blood transfusion, organ transplantation and congenital transmission. The disease is endemic in 21 countries in Latin America, where 100 million people are at risk.

It is estimated 8 million people are infected in the region but 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.

The current Chagas disease portfolio includes:


Research
Research

 

Early stage drug screening and lead optimization activities to ensure that new compounds and back-up molecules (oxabolore series and nitroimidazoles) are available and advance through the drug development pipeline.

 

Translation
Translation

Three projects are in the translation phase:

  • A Phase II proof-of-concept (PoC) with the New Chemical Entity (NCE) fexinidazole has begun this year in Bolivia and will include 140 adults with chronic intermediate Chagas disease.

Also, results of the recent study on the NCE E1224 (fosravuconazole, a pro-drug of ravuconazole from the azoles class of coumpounds discovered and developed in partnership with Eisai Co. Ltd) – which was the first placebo controlled, double-blind trial of benznidazole and the first Phase II trial to be undertaken in Bolivia – showed that the drug offered no perspective as a monotherapy for Chagas disease, but provided solid data on the efficacy of benznidazole. On this basis, the DNDi Chagas disease programme designed two additional studies for the treatment of adult patients with chronic indeterminate Chagas disease:

  • A Phase II PoC of new combination regimens of benznidazole and E1224, in Bolivia and Argentina, to be performed following a drug-drug interaction study testing the PK, safety and tolerability of concomitant administration of the two drugs.

Pre-clinical and clinical studies are ongoing to identify and validate potential biological markers of therapeutic response in Chagas to support clinical development.
Implementation
Implementation

 

Implementation and access to treatments:

  • DNDi continues to support implementation efforts and registration of the paediatric formulation of benznidazole that was delivered in 2011 by Lafepe in Brazil. The formulation was registered in Brazil (2011) and was included on the WHO Essential Medicine List for children (2013). DNDi is also working closely with Mundo Sano Foundation in Argentina on a second source of the pediatric dosage form of benznidazole. In addition, considering that only an estimated 1% of people affected are treated, DNDi is also partnering, notably through the Global Chagas Disease Coalition, to advocate for scaling up diagnosis and treatment for all Chagas disease patients, with existing health tools.

 

By 2018, from its Chagas-specific portfolio, DNDi aims:

  • To deliver a new,effective and safer oral therapy (in monotherapy or combination) for the treatment of chronic indeterminate Chagas disease, ideally also effective against the acute form of the disease.
  • To stimulate the development of biomarkers to gain understanding of disease progression and facilitate the development of tools for evaluation of treatment response to support drug development.


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