DNDi and our partners are working to develop safe, affordable treatments to prevent devastating amputation and disability – and to improve access for all people in need. With evidence from our Phase II trial showing the efficacy of treatment with itraconazole and fosravuconazole, the latter having practical advantages, we are now working to help facilitate access to the two treatments and close epidemiological knowledge gaps in key endemic countries.
Our progress in 2024 includes:
Discovery
MycetOS: Drug discovery efforts continued throughout 2024, with Erasmus MC, University College London, University of Sydney, and the University of Bayreuth closely collaborating to find new drugs for the treatment of fungal mycetoma. Several high school students participated by making novel analogues under the supervision of University College London and the University of Sydney, and the biological activity of these molecules was tested at Erasmus MC. Although the focus of the chemical synthesis activities remained on fenarimols, ketoximes, aminothiazoles, and benzoxazoles, additional biological experiments were performed to identify novel drug targets. These included screening additional compound libraries and using transcriptomic and genomic approaches to unravel the genes transcribed during grain formation and the kinome of Madurella mycetomatis. Several articles were written and submitted for publication.
Development
Fosravuconazole: The results of the Phase II clinical trial were published in The Lancet Infectious Diseases in November 2024 and showed that treatment with either of the two dose levels of fosravuconazole was not superior to itraconazole, and the two dose levels had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug-drug interactions compared with relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery, is warranted.
Implementation
New treatments for mycetoma: A field visit to Ethiopia (Bahir Dar, Dessie, Boru Meda, Arba Minch) was conducted in April to assess current medical practices and local treatment needs, establish partner networks, and collect existing epidemiological data. Retrospective data collection of mycetoma cases in medical and laboratory records for a 10-year period (2014-2023) began in July for Senegal and September for India, with the aim of providing information on existing, documented mycetoma cases. In December, a burden of disease study was started involving house-to-house visits from health extension workers in four regions of Ethiopia (Afar, Amhara, Southern Nations and Tigray) to screen patients for mycetoma and refer suspected cases to the nearest health facility for diagnosis and management.
Photo credit: Kumerra Gemechu-DNDi
