R&D MODEL & PORTFOLIO
New benznidazole regimens/ combinations
PROJECT START: December 2013 OVERALL OBJECTIVE: Develop a new improved regimen of benznidazole and a benznidazole/fosravuconazole combination treatment regimen for chronic Chagas disease 2015 OBJECTIVE: Initiate plans for Phase II studies for simpler benznidazole monotherapy regime or in combination with fosravuconazole
of-concept trial carried out in 2013 showed that fosravuconazole (previously known as E1224) had good safety and was effective at clearing the parasite, but efficacy was not sustained. A Phase I drug-drug interaction study, undertaken in 2014 in 28 healthy human volunteers in Buenos Aires, Argentina, assessed the safety and pharmacokinetic interactions of fosravuconazole and benznidazole administered separately and in combination: no major clinically relevant safety or tolerability issues were identified. A proof of concept study in approximately 270 patients with chronic Chagas disease will determine if the safety and tolerability issues of benznidazole can be managed by reduced doses and treatment duration, or by combining it with fosravuconazole. The protocol for this study, composed of eight arms with benznidazole in monotherapy or in combination with fosravuconazole at selected doses and treatment durations versus placebo, was finalized in 2015. Sites in Argentina, Bolivia, and Spain were identified, and patient recruitment is expected to start in 2016.
MAIN PARTNERS: ARGENTINA: Fundación Mundo Sano and ELEA; Administración Nacional de Laboratorios e Institutos de Salud (ANLIS); Instituto Nacional de Epidemiología Dr Fatala Cháben; Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” - INGEBI-CONICET; Centro de Chagas y Patologia Regional, Hospital Independencia, Santiago del Estero; Fundación Para el Estudio de las Infecciones Parasitarias y Enfermedad de Chagas (FIPEC); BOLIVIA: Collective of Applied Studies and Social Development (CEADES); Universidad Autónoma Juan Misael Saracho; Universidad Mayor de San Simon; SPAIN: IS Global, Centre de Recerca en Salut Internacional de Barcelona (CRESIB); Hospital General de Valencia; SPAIN/BOLIVIA: Platform of Integral Care for Patients with Chagas Disease; JAPAN: Eisai Co. Ltd
Benznidazole, the standard treatment for Chagas, had sustained efficacy until 12 months post-therapy, but was associated with side effects that resulted in treatment discontinuation. A proof-
PROJECT START: December 2013 OVERALL OBJECTIVE: Evaluate fexinidazole for treatment of chronic Chagas disease 2015 OBJECTIVE: Conclude the 12-month assessments of the PoC
MAIN PARTNERS: ARGENTINA: Instituto de Investigaciones en
Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” INGEBI-CONICET; BOLIVIA: Collective of Applied Studies and Social Development (CEADES); Platform of Integral Care for Patients with Chagas Disease, Tarija and Cochabamba; Universidad Autónoma Juan Misael Saracho; Universidad Mayor de San Simon; SPAIN: Centre de Recerca en Salut Internacional de Barcelona (CRESIB)
Phase II and proceed to the data cleaning and analysis
47 patients recruited at 2 sites
Comprehensive pre-clinical results evaluation of fexinidazole supported its clinical evaluation in patients. A Phase II Proof-of-Concept trial was initiated in adult patients with chronic Chagas disease in Bolivia in 2014, but after recruiting 47 participants, the study was interrupted due to safety and tolerability issues. A safety review did not identify the same frequency or severity of adverse events for fexinidazole when used in other indications. Patient monitoring continued for 12 months post-treatment to assess if there was sustained suppression of parasites as assessed by PCR and the final study results are expected in early 2016.
DNDi Annual Report 2015 › 39