Developed by DNDi and partners and added to the World Health Organization (WHO) Essential Medicines List in 2019, the first all-oral cure for sleeping sickness, fexinidazole, is now being donated by Sanofi to WHO for distribution in T.b. gambiense-endemic countries. DNDi is supporting pharmacovigilance and training to scale up access to this new treatment while advancing clinical development of acoziborole – a potentially game-changing, single-dose oral treatment that could provide an even better treatment option and facilitate sustained elimination of the disease.
Short-term strategies to develop better treatment regimens using existing drugs progressed, with Phase IIb/III studies in Africa testing new regimens for VL and post-kala-azar dermal leishmaniasis (PKDL) and a Phase II study in South Asia testing a new regimen for PKDL. Results from HIV/VL Phase III studies in Ethiopia and India were presented to national and international authorities to inform review of HIV/VL treatment guidelines. In addition, multiple new chemical entities have progressed in pre-clinical and Phase I studies, marking significant progress towards DNDi’s long-term goal of developing an entirely new generation of all-oral drugs for VL.
Preliminary results from a Phase II study in Latin America showed the combination of thermotherapy with a shorter course of oral miltefosine to be significantly better than thermotherapy alone for the treatment of uncomplicated CL in the Americas. Planning for first-in-human studies is underway for CpG-D35, a novel immunomodulator designed to promote the immune system’s response to the parasitic infection that causes CL.
Preliminary results of a Phase II study evaluating new therapeutic regimens of benznidazole showed that all treatment arms were effective and had good safety profiles. The two-week course of treatment with benznidazole alone was particularly promising. Based on these results, DNDi is planning to run an international, multisite confirmatory Phase III study.
With first-in-human studies for emodepside in healthy volunteers successfully completed, preparations are underway to run a Phase II clinical trial at two sites in Ghana. In the Democratic Republic of the Congo (DRC), training and trial site renovations are advancing ahead of a Phase II proof-of-concept study for TylAMac, which was shown to be safe and well tolerated in Phase I studies. And new efforts to identify novel treatments against ‘nematode’ worms have kicked off following the launch of a new multidisciplinary consortium: the Helminth Elimination Platform (HELP).
In Sudan, the first-ever double-blind, randomized clinical trial for fungal mycetoma is ongoing and had enrolled 101 patients by January 2020. The primary objective of the study is to demonstrate the superiority of the new chemical entity fosravuconazole over the current standard treatment, itraconazole.
DNDi’s pharmaceutical partner Cipla submitted the ‘4-in-1’ fixed-dose combination treatment for infants and young children with HIV to the US Food and Drug Administration (FDA) for tentative approval. The easy-to-administer, strawberry-flavoured treatment requires no refrigeration and is a great improvement over the current treatment option: a bitter-tasting syrup with high alcohol content. Cipla will price the 4-in-1 at under USD 1 a day for children weighing up to 14 kg.
Following excellent results from the first stage of a Phase II/III trial evaluating the ravidasvir/sofosbuvir combination, a second stage of the study in Malaysia and Thailand is testing the treatment in patients with hepatitis C genotypes 1a, 1b, 2, 3, and 6 to further establish the pan-genotypic profile of ravidasvir. Plans to submit for the conditional registration of ravidasvir with the Malaysian National Pharmaceutical Regulatory Authority are underway, with filing expected in mid-2020.
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