DNDi aims to develop an effective, safe, affordable, and simpler curative treatment. There is currently no effective cure for fungal mycetoma.

DNDi’s current mycetoma portfolio includes:

R&D discovery stage iconDiscovery

  • MycetOS: A list of current targets for Open Pharma project MycetOS has been compiled and opportunities given to researchers interested in working on them. Two participating institutions from the Open Synthesis Network have received preliminary data and are working to identify new compounds with potential activity against mycetoma.

R&D development stage iconDevelopment

  • Fosravuconazole: The first-ever double-blind study to determine whether the new chemical entity fosravuconazole could be an effective and affordable treatment for eumycetoma is ongoing. By January 2020, 101 patients had been enrolled in the study, which should reach the targeted enrollment of 165 patients by the end of 2020. A Data and Safety Monitoring Board (DSMB) meeting was held in 2019 after the study reached the threshold for interim analysis (84 participants). The DSMB reviewed study data and decided to continue with all three treatment arms (200 mg vs 300 mg of fosravuconazole weekly vs daily itraconazole).

Photo credit: Neil Brandvold-DNDi

Click here to read the article

The Mycetoma Research Centre (MRC) has completed work to launch a specialized laboratory in Sudan, situated at the Wad Onsa Regional Mycetoma Centre (WORMC) in Sennar State. Now fully operational, the laboratory was constructed with support from DNDi and opened officially by the Governor of Sennar State in early January 2020.

The MRC has partnered with DNDi since 2016 to conduct the first-ever mycetoma clinical trial for fosravuconazole, a potential new treatment for fungal mycetoma. Until this year, most specialized mycetoma lab procedures in Sudan were carried out at the MRC or at Soba Hospital in the capital city, Khartoum. This meant that patients had to travel long distances – from as far away as endemic Sennar State, about 400 kilometres from the capital – to be tested for mycetoma.

The new laboratory at WORMC is equipped for microbiological testing and has an excellent storage facility for reagents and samples. A portable ultrasound machine also is now available, both for use in the centre and for outreach activities in the surrounding villages. The imaging and laboratory equipment will improve the quality of medical services offered by the MRC for the whole community and support patient recruitment for the ongoing mycetoma treatment clinical trial.

Healthcare worker examining a patient

Doctors doing an operation on the foot

Photo credit: Mycetoma Research Centre

Click here to read the article

Click here to read the article

Klicken Sie hier, um den Artikel zu lesen / Cliquez ici pour lire l’article / Clicca qui per leggere l’articolo

DNDi aims to deliver:

  • A new safe, effective and affordable treatment for patients with eumycetoma.

DNDi’s current mycetoma portfolio includes:

Research

Discovery

  • MycetOS: In February 2018, the Mycetoma Open Source (MycetOS) project was launched by the University of Sydney, Erasmus MC, and DNDi to use an ‘Open Pharma’ approach to discover compounds that could lead to new treatments for patients suffering from fungal mycetoma (eumycetoma). MycetOS will progress drug discovery efforts through community-driven, in-kind scientific contributions and a robust, fully transparent online presence. All ideas and results will be published immediately in real time to an open-access database. Results and the associated data form the starting point for the MycetOS community, which communicates on Twitter (@MycetOS) and uses a dedicated subreddit forum for transparent interactive discussion, and github for sharing data and key project files.

Development

   Development

    One project in the development phase:

  • Fosravuconazole: In March 2017, the Mycetoma Research Centre (MRC), a WHO Collaborating Centre, in Khartoum, Sudan, began recruiting patients into the first-ever double-blind, randomized clinical trial for eumycetoma (fungal mycetoma). The clinical trial, which will recruit 138 patients, is studying the efficacy of weekly treatment with the anti-fungal fosravuconazole in moderate-sized lesions in comparison with the standard of care, 400mg of itraconazole daily, over 12 months of treatment.

    Fosravuconazole, an orally bioavailable azole developed for onychomycosis by Eisai Ltd (Japan) that is also under development by DNDi for Chagas disease, could be an effective and affordable treatment for eumycetoma. Its pharmacokinetic properties are favourable, and its toxicity is low.

    Following slower than anticipated recruitment, a protocol review and amendment was conducted in 2018 to extend the inclusion criteria in relation to lesion size and site, and age range of participants. By January 2019, 84 patients had been enrolled, reaching the threshold for interim analysis. This analysis will determine which of two treatment arms will be retained for the remainder of the trial (200mg vs 300mg of fosravuconazole weekly). 

Photo credit: Neil Brandvold-DNDi

Former DNDi Medical Director Dr Nathalie Strub-Wourgaft takes over leadership of NTD programme

DNDi is pleased to announce the appointment of Dr Nathalie Strub-Wourgaft as the new Director of Neglected Tropical Diseases. She will assume her new role as NTD Director and member of DNDi’s Executive Team as of 1 July 2018.

Dr Strub-Wourgaft has been a pillar of scientific expertise at DNDi for the last nine years, bringing strong medical and scientific credibility to the organization in R&D clinical development. As the Medical Director, she developed and strengthened the capacity and expertise of DNDi in Regulatory Affairs, Pharmacovigilance and Quality Assurance. She played an active role in promoting mycetoma as the 18th NTD in the WHO list. Her team’s latest achievement was overseeing the clinical development and dossier preparation for fexinidazole, the first oral treatment for African sleeping sickness, which was submitted by industrial partner Sanofi to the European Medicines Agency for review in January of this year.

Dr Strub-Wourgaft came to DNDi in 2009 with more than 15 years of clinical development experience, including as Director, Clinical Development at Trophos, Medical Director for the French office of Aspreva, and several years at each of Pfizer and Lundbeck. Dr Strub-Wourgaft earned her MD at Necker Hospital, Université René Descartes in Paris in 1983.

In her new role, Dr Strub-Wourgaft will provide strategic leadership and direct oversight of DNDi’s five NTD teams, which are working to deliver new and improved treatment regimens for human African trypanosomiasis, leishmaniasis, Chagas disease, filarial diseases, and mycetoma.

Photo credit: Neil Brandvold-DNDi

by Lim W, Melse Y, Konings M, Phat Duong H, Eadie K, Laleu B, Perry B, Todd M, Ioset J-R, and van de Sande W. PLOS Neglected Tropical Diseases 2018, 12(4): e0006437, doi: 10.1371/journal.pntd.0006437ER.

Summary: The authors describe a study in which 800 diverse drug-like molecules were screened for activity against eumycetoma, 215 of which were active in vitro. One of the most potent compounds, a fenarimol analogue for which a large analogue library is available, led to the screening of an additional 35 compounds, rendering four further hits. The potency of these hit compounds was assessed in vivo using a Galleria mellonella larvae model infected with M. mycetomatis; the results were promising for several hits in terms of prolonged larval survival and/or reduced fungal burden. These results are the starting point of an Open Source Mycetoma (MycetOS) approach in which members of the global scientific community are invited to participate and contribute as equal partners.

Click here to read the article / PDF

Click here to read the article