The Week [3 March 2020]
“Clinical trials on for an advanced oral drug for kala-azar”
Pharmaceutical Business Review [26 February 2020]
“Novartis, DNDi to jointly develop LXE408 for visceral leishmaniasis”
Science Africa [26 February 2020]
“Novartis and DNDi targets to treat visceral leishmaniasis”
Added to the 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 visceral leishmaniasis (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 toward DNDi’s long-term goal of developing an entirely new generation of all-oral drugs for VL.
For cutaneous leishmaniasis (CL), 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.
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, showing 83% efficacy while cutting treatment time by 75% compared to the standard eight-week treatment, with no patients discontinuing treatment due to side effects. Based on these results, DNDi is planning to run an international, multi-site 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 Congo, 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. The study’s targeted enrollment of 165 patients should be reached by the end of 2020.
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 one dollar 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 infected 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.
The Hindu Business Line [25 February 2020]
“Global clinical trial for drug to treat Kala Azar to take place in 2021”
Africa Link [25 February 2020]
“Novartis and DNDi collaborate to develop new treatment for visceral leishmaniasis.”
Basel, Switzerland – 25 February 2020
- LXE408 is a first-in-class compound, discovered at Novartis with financial support from the Wellcome Trust
- Novartis is responsible for completing Phase I clinical trials and has committed to maximizing access in endemic countries, once approved
- DNDi will lead Phase II and III clinical development, starting in India with additional trials planned in East Africa
- Leishmaniasis, which is transmitted by the sandfly, affects over one billion people; visceral leishmaniasis, the most serious form of the disease, affects an estimated 50 000 to 90 000 people per year
Novartis and DNDi have signed a collaboration and licence agreement to jointly develop LXE408, as a potential new oral treatment for visceral leishmaniasis, one of the world’s leading parasitic killers.