New chemical compound shows promising results against drug-resistant malaria parasites

The new chemical compound ACT-451840 is highly effective against most deadly malaria parasites in humans. It is also active against those parasites that have developed resistance against the standard therapies. The findings, published today in the journal PLOS Medicine, come from the Swiss Tropical and Public Health Institute (Swiss TPH) in collaboration with partners from industry and academia.

Treating malaria is a global challenge. Resistance against artemisinin-based combination therapies has recently been detected in Southeast Asia, threatening the impact of standard therapies on malaria. Developing new and highly efficient antimalarials is, therefore, badly needed.
The new chemical compound ACT-451840 could be a new and effective weapon in the fight against the disease. In preclinical studies, the compound proved to be active against P. falciparum and P. vivax – the parasites responsible for the deadliest forms of malaria in humans.


“One of the huge advantages of ACT-451840 is that its mode of action differs from that of other chemical compounds”, says Sergio Wittlin, project leader at Swiss TPH. ACT-451840 belongs to a different chemical class of antimalarials than the standard artemisinin, which allows it to successfully tackle artemisinin-resistant strains. “With its properties, ACT-451840 could replace artemisinin in future combination therapies”, says Wittlin. Initial clinical studies testing the effects of ACT-451840 in humans showed good tolerability and fast action.


Transmission-blocking characteristics 
ACT-451840 has another decisive advantage: it is also active against sexual-stage parasites (gametocytes).  Only at this stage of the life cycle are parasites infectious to mosquitoes. ACT-451840 is able to block the parasite’s transmission from humans to mosquitoes, thereby containing the spread of the disease.


Further clinical studies depend on new partners
The development and characterisation of ACT-451840 is the result of a ten-year research collaboration between public and private partners, supported by the Medicines for Malaria Venture (MMV). Actelion Pharmaceuticals Ltd. was responsible for the compound’s discovery and first clinical trials. Swiss TPH and other academic partners tested the compound in vitro against the parasites at different stages of their life cycle. To further develop ACT-451840 and to fund the clinical phase II and III studies, new sponsors have to be found. Additional financial investments are needed to successfully develop ACT-451840 into an effective antimalarial drug. “Developing the compound is of huge importance”, says Sergio Wittlin, for the spread of resistance against traditional drugs is an increasing threat. No new chemical class of antimalarials has been registered in the last 20 years.


About Malaria
Every 30 seconds, a child dies of malaria. This disease costs Africa 12 billion dollars (US) a year in health-care costs and lost productivity, particularly in the agricultural sector. The rapid spread of drug-resistance has become a global threat. WHO set the aim of eradicating the disease by 2030. Therefore, new investments in developing drugs and vaccines and in fighting the mosquitoes are needed. The new compound ACT-451840 could play a central role in this endeavour.


Amélie Le Bihan, Ruben de Kanter, Iñigo Angulo-Barturen, Christoph Binkert, Christoph Boss, Reto Brun, Ralf Brunner, Stephan Buchmann, Jeremy Burrows, Koen J. Dechering, Michael Delves, Sonja Ewerling, Santiago Ferrer, Christoph Fischli, Francisco Javier Gamo–Benito, Nina F. Gnädig, Bibia Heidmann, María Belén Jiménez-Díaz, Didier Leroy, Maria Santos Martínez, Solange Meyer, Joerg J. Moehrle, Caroline L. Ng, Rintis Noviyanti, Andrea Ruecker, Laura María Sanz, Robert W. Sauerwein, Christian Scheurer, Sarah Schleiferboeck, Robert Sinden, Christopher Snyder, Judith Straimer, Grennady Wirjanata, Jutta Marfurt, Ric N. Price, Thomas Weller , Walter Fischli, David A. Fidock, Martine Clozel, Sergio Wittlin, Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose–Efficacy Modeling, PLoS Medicine (2016): DOI:10.1371/journal.pmed.1002138


Sergio Wittlin , Head of Malaria Drug Discovery Group, Swiss Tropical and Public Health Institute (Swiss TPH), Sergio.wittlinanti spam bot@unibasanti spam bot.ch

Amélie Le Bihan, First author, Swiss Tropical and Public Health Institute (Swiss TPH), amelie.j.lebihan@gmail.com






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