patients

R&D MODEL & PORTFOLIO
MYCETOMA
DEVELOPMENT
Fosravuconazole
PROJECT START: September 2015
OVERALL OBJECTIVE: Conduct a randomized controlled clinical
trial to investigate the efficacy of fosravuconazole compared to the
current treatment, itraconazole.
Treating eumycetoma is a challenge. Currently, the antifungals
ketoconazole and itraconazole are the only therapies available
but these are expensive, ineffective, and have serious side
effects. Patients often have to undergo amputation, and often
more than once, sometimes resulting in death. Safe, effective
antifungal agents that are appropriate for use in rural settings
are urgently needed.
Fosravuconazole (E1224), an orally bioavailable azole that is
under development for Chagas disease, may be an effective
and affordable treatment for eumycetoma. Fosravuconazole,
a prodrug, is rapidly converted to ravuconazole, which has
been shown to have potent in vitro activity against one of the
causative agents of eumycetoma, Madurella mycetomatis. Its
pharmacokinetic properties are favourable and its toxicity
is low. A randomized controlled trial will be conducted with
the WHO Collaborating Centre on Mycetoma in Khartoum
to study the efficacy of fosravuconazole in moderate lesions
in comparison with the current treatment, itraconazole. The
primary objective of this double-blinded, randomized, singlecentre
study (with an interim analysis at three months) will be
to demonstrate superiority of fosravuconazole over itraconazole
after 12 months treatment. The study is due to begin in 2016.
MAIN PARTNERS: Eisai Co. Ltd, Japan; Erasmus Medical Center, The
Netherlands; Radboud University Medical Center, Nijmegen, The
Netherlands; Mycetoma Research Centre (MRC), Soba University
Hospital, Khartoum, Sudan; Institute of Endemic Diseases (IEND),
Khartoum University, Sudan
Mustafa Alnour Alhassan, a young university student aged 26, with
mycetoma, sitting on the rickshaw he took to the Mycetoma Research
Centre (MRC) in Khartoum, Sudan. Despite the treatments he received,
the flesh-eating fungal disease continued to progress and his leg was
amputated in July 2015. The disease unfortunately spread to his groin
and lungs. He died in March 2016.
52 › DNDi Annual Report 2015