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 2023 includes:
Discovery
MycetOS: Drug discovery efforts continued throughout 2023, with Erasmus MC, University College London, University of Sydney, and the University of Bayreuth closely collaborating to find new drugs for mycetoma. Participants with new expertise joined the MycetOS community, allowing for modelling activities to be incorporated into the collaboration. 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. Our focus remained on fenarimols, aminothiazoles, antifolate inhibitors, benzimidazoles, and ketoximes, and additional compound libraries were also screened to identify novel hits. In the fenarimol series, a correlation was discovered between logD and in vivo efficacy in an invertebrate model.
Development
Fosravuconazole: The results of DNDi’s the Phase II clinical trial were presented at the 13th European Congress on Tropical Medicine and International Health (ECTMIH), held in November 2023 in Utrecht, Netherlands. The clinical study report was finalized and results are expected to be published in 2024. The long-term follow-up study assessing the recurrence rate of mycetoma in clinical trial participants in the Phase II trial was stopped in 2023 due to socio-political unrest in Sudan. A total of 51 participants were included in the follow-up study. Recurrence rates remained low and no serious adverse events were reported.
Implementation
New treatments for mycetoma: Three expert meetings organized by DNDi in Nairobi, Geneva, and Utrecht brought together representatives from Africa, South America, South Asia, and Europe to set out a framework for much-needed epidemiological studies to address knowledge gaps on the burden and distribution of mycetoma. The meetings also examined important aspects of clinical trial design and drug development, including the need to develop medicines that are not only simpler and more effective, but also suitable for children and women of childbearing potential. In July, a field visit was conducted in Senegal to assess current practices and local treatment needs, establish partner networks, and collect epidemiological data.
Photo credit: Lameck Ododo-DNDi
