The Drugs for Neglected Diseases initiative (DNDi) is pleased to announce its 2023 Projects of the Year, which recognize DNDi teams and partners for outstanding progress in the areas of pre-clinical and clinical research. Nominated by the DNDi Scientific Advisory Committee and selected by the DNDi Executive Board, the 2023 awards recognize two projects from among more than 40 in DNDi’s R&D portfolio.
Partners and staff collaborating on the 2023 Projects of the Year were celebrated during a dedicated session of the 41st meeting of the DNDi Scientific Advisory Committee on 6 October.
‘From investigating new compounds to fill a long-empty research and development pipeline for Chagas disease to conducting the first clinical trial for neglected mycetoma patients, our 2023 projects of the year are prime examples of DNDi’s work to tackle innovation challenges from the laboratory bench to patient bedside,’ said Dr Laurent Fraisse, Director of R&D, DNDi. ‘We are very grateful for the expertise and dedication our colleagues and partners are bringing to these important initiatives and thank them for their commitment to advancing medical innovation for neglected patients.’
Pursuing better treatments for a silent killer
Early discovery for Chagas disease – 2023 Project of the Year in pre-clinical research
Only two drugs – discovered half a century ago – are available to treat Chagas disease, a potentially fatal parasitic illness transmitted by insects known as ‘kissing bugs’, which hide in cracks in walls and furniture. If not treated, Chagas can cause irreversible, life-threatening damage to the heart and other vital organs. Endemic in Latin America and the southern US, it is also present in Europe, Japan, and Australia. The current treatment for the disease is effective but lasts eight weeks and sometimes has serious side effects. Better and safer treatments are urgently needed.
Applying multiple technologies and research strategies, DNDi and partners’ early drug discovery teams have made significant progress in screening chemically diverse compound libraries – including natural product collections – and identifying novel chemical entities as new starting points to feed the early drug discovery pipeline for Chagas disease.
DNDi is grateful to the many partners who have advanced this critical early work toward discovering and developing all new treatments for Chagas. These include Mitsubishi Tanabe Pharma Corporation for its active participation in the early-stage development of a novel lead series identified from the screening of a proprietary Mitsubishi Tanabe compound collection of synthetic origin, Fundación Medina and Institut Pasteur Korea for their support for natural products hit identification and parasite painting assays, and the University of Geneva for their contribution of enabling technologies for natural products hit identification.
We are also very grateful for the vital expertise in parasitology brought to bear by our screening platform partners – Institut Pasteur Korea, Nagasaki University, Swiss Tropical and Public Health Institute, and University of Dundee – who have recently identified over 20 new active series against T. cruzi, the Chagas disease parasite, via high-throughput screening of compound libraries.
Progress against the ‘most neglected of neglected diseases’
Fosravuconazole for mycetoma – 2023 Project of the Year in clinical research
Mycetoma is a devastating infection that can destroy muscle and bone. The fungal version of the disease, known as eumycetoma, leads to horrible deformities and disability. The disease occurs in the so-called mycetoma belt, between latitudes 15° S and 30° N, but its global burden is unknown. There is no effective cure for fungal mycetoma, and amputation is common when infection is severe or treatment fails. A new drug is urgently needed.
In 2017, DNDi and the Mycetoma Research Center (MRC) in Khartoum, Sudan began enrolling patients in the first-ever double-blind, randomized Phase II clinical trial for fungal mycetoma. The initial trial studied the efficacy of a weekly dose of fosravuconazole – an anti-fungal azole compound originally discovered for various fungal infections including onychomycosis by Eisai Co. Ltd. – compared to daily treatment with itraconazole, in patients requiring surgery.
Results presented in 2022 showed that fosravuconazole and itraconazole had significant and similar levels of efficacy, with fosravuconazole having practical advantages – including weekly as opposed to twice-daily administration, no need to administer with food, and no contraindication to other drugs. With a favourable safety profile, fosravuconazole showed efficacy at two tested doses. A follow-up study was initiated to determine relative rates of long-term disease recurrence.
DNDi, the Sudanese MRC, and the Japanese pharmaceutical partner Eisai, who provided fosravuconazole for the trial, initiated discussions in 2022 with the regulatory authorities in Sudan ahead of submitting it for approval. Given the urgent medical and public health need, the Ministry of Health of Sudan authorized the importation of fosravuconazole for patient treatment at the MRC – although the full impact of current unrest on patients with mycetoma in the country is not yet known.