Novel Novartis malaria compound shows potential to be effective against infections resistant to all currently available antimalarial drugs

News Hour:

Novartis published proof of concept study results in the New England Journal of Medicine showing that its new antimalarial compound, KAF156, demonstrated activity against both vivax and falciparum malaria, including artemisinin-resistant parasites.

Malaria is a life-threatening disease primarily caused by parasites (Plasmodium falciparum and Plasmodium vivax) transmitted to people through the bites of infected Anopheles mosquitos. Each year, it kills nearly half a million people, most of whom are children. Artemisinin-based combination therapies (ACTs), such as Coartem®, are currently the standard of care against falciparum infections. Yet, rising resistance to artemisinin and decreasing partner drug efficacy in Southeast Asia threatens the global control of Plasmodium falciparum malaria. This is why new drugs are needed.

“KAF156 is a potential game-changing therapy against malaria,” said Thierry Diagana, Head of the Novartis Institute for Tropical Diseases (NITD). “It acts against the two main parasites responsible for the majority of malaria deaths and against the blood and liver stages of the parasite’s lifecycle. Novartis leads two of the four most advanced malaria development programs worldwide. If the programs are successful, they could help address the emerging issue of multidrug resistance.”

KAF156 is the first compound from a novel class of drugs called imidazolopiperazines whose mechanism of action is still being characterized, but may be related to a previously uncharacterized gene (Plasmodium falciparum cyclic amine resistance locus, Pfcarl). In line with WHO guidance that antimalarials be co-formulated to mitigate the risk of parasite resistance development, it is expected that KAF156 will become part of a combination regimen when used to treat malaria.

From March to August 2013, a phase II, open-label, two part study was conducted in five centers in Thailand and Vietnam to assess KAF156 in adult patients with acute uncomplicated P.vivax (11 patients) or P.falciparium (10 patients) malaria. Multiple dose (400 mg once daily for 3 days) cohorts assessing parasite clearance rates were followed by a single dose cohort in falciparum malaria (800 mg) assessing 28 day cure rates (22 patients). Researchers saw that KAF156 resolves signs and symptoms of illness and cleared parasitemia rapidly in both vivax and falciparum malaria patients, including infections with artemisinin-resistant parasites.

“We are currently losing the battle against resistance in the Great Mekong Sub-region. In the past resistance has spread from this region and caused millions of deaths in Africa and India. The discovery and development of new safe and effective antimalarial drugs which are unrelated to those we currently use and do not share their resistance mechanisms, is essential if we are to curb this threat, and to control and ultimately eliminate malaria,” said Professor Nick White, from the Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Teams working as part of a joint research program with the Novartis Institute for Tropical Diseases, the Genomics Institute of the Novartis Research Foundation, and the Swiss Tropical and Public Health Institute, discovered KAF156.  Research was supported by the Wellcome Trust, the Singapore Economic Development Board, and Medicines for Malaria Venture (MMV). Novartis will lead the development of KAF156 with scientific and financial support from MMV (in collaboration with the Bill & Melinda Gates Foundation).

Md. Rafiuzzaman Sifat, a CSE graduate turned into journalist, works at News Hour as a staff reporter. He has many years of experience in featured writing in different Bangladeshi newspapers. He is an active blogger, story writer and social network activist. He published a book named 'Se Amar Gopon' inEkushe boi mela Dhaka 2016. Sifat got a BSc. from Ahsanullah University of Science & Technology, Bangladesh. He also works as an Engineer at Bangla Trac Communications Ltd. As an avid traveler and a gourmet food aficionado, he is active in publishing restaurant reviews and cutting-edge articles about culinary culture.
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