Novartis announced yesterday that its scientists at the Novartis Institute for Tropical Diseases (NITD), in collaboration with researchers from the Genomics Institute of the Novartis Research Foundation (GNF), the Swiss Tropical and Public Health Institute and The Scripps Research Institute have discovered a novel compound that shows promise as a next generation treatment for drug resistant malaria. Major support for the project was provided by the Wellcome Trust, the Medicines for Malaria Venture (MMV), A*STAR, Singapore and the US government.
Published this week in Science, the findings demonstrate that the antimalarial candidate, spiroindolone NITD609, is effective against both strains of the malaria parasite, Plasmodium (P.) falciparum and P. vivax.
Through a novel mechanism, NITD609 rapidly clears plasmodium in a malaria mouse model and shows pharmacological properties compatible with a once-daily dosing regimen.
According to the World Health Organization (WHO), in 2008 there were approximately 247 million cases of malaria, causing nearly one million deaths, mostly among young children in Africa. Although malaria is preventable and curable, it is estimated that in Africa, a child dies every 45 seconds from the disease.
"Malaria remains a scourge," said Mark Fishman, president, Novartis Institutes for BioMedical Research. "The parasite has demonstrated a frustrating ability to outwit new medicines, from quinine to today's unsettling increased tolerance to artemisinin derivatives. We are delighted that our scientists could provide this potential new malaria therapy, based on an unprecedented chemical structure and directed to a novel target."
Further regulatory pharmacological and safety evaluation is currently ongoing and, provided the outcome of these studies is favorable, the compound could progress to Phase I human trials.
A novel mechanism of action
Despite significant advances in Plasmodium genome biology, the identification and validation of new drug targets has proven challenging. In the Science paper the research team outlines how they identified a potential target by identifying mutations that decreased the parasite's sensitivity to this novel compound class.