The Novartis Malaria Initiative: lessons from a
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Buoyed by progress of the past decade, major international agencies and many governments are now aiming for elimination of malaria, the interruption of mosquito-borne transmission to eliminate the local reservoir of parasites. Currently 32 nations are pursuing an elimination strategy, with success a prospect for the next decade provided they are adequately supported. Elimination is a more distant prospect for many countries, however, reflecting both the high intensity of local transmission and substantial movement of people across borders which creates the constant potential for malaria importation.
Innovation again promises to be the driving force in elimination. Sir Richard Feachem, the former executive director of the global Fund and currently director of the Global Health Group at the University of California, San Francisco, says: "The speed of progress will depend on the development and deployment of better drugs, better diagnostics and a series of increasingly effective vaccines."
Novartis aspires to contribute to elimination of malaria and has embarked on a number of important research programs and clinical studies. Today, the declining number of malaria cases and widening use of rapid diagnostic tests are helping to reduce intensity of malaria transmission. According to experts, some form of focused screening and availability of novel medicines will be essential to elimination of malaria.
Gametocytes, the sexual stage of the malaria parasite, do not cause malaria symptoms but are responsible for transmission of the disease when ingested by a mosquito in a blood meal and inoculated into the next person bitten. Several studies have confirmed that rapid clearance of gametocytes by Coartem helps to break the cycle of transmission between the mosquito and human hosts. In Burkina Faso, Novartis is conducting the first comprehensive study to evaluate the effect of mass screening followed by targeted treatment of asymptomatic patients. If effective, this strategy could lead to substantially decreased parasite transmission.
In recent years, there also has been growing concern that the poor quality of some antimalarial medicines available in many countries not only could jeopardize the health of patients but also hasten the emergence of malaria parasites resistant to ACTs.
The WHO has presented a global plan for containment of artemisinin resistance. There may, however, be a limited window "for containing or eliminating artemisinin resistance before it spreads to high transmission areas, endangering all recent advances in malaria control," a recent WHO report warns.
Novartis has never developed or marketed monotherapies for malaria, recognizing that the unique properties of artemisinins must be protected by a longer-acting partner drug. Lumefantrine, the partner compound in Coartem, has never been deployed as a monotherapy and no resistance has developed in Africa so far. Nevertheless, the threat of artemisinin resistance has triggered a concerted search for new drugs with novel mechanisms of action. Last year, in the journal Science, Novartis researchers reported the discovery of an antimalarial drug candidate in a new class of compounds known as spiroindolones.
The compound, known by the research number KAE609, suppresses protein synthesis in malaria parasites and displays good antimalarial activity. KAE609 has advanced to the initial phase of testing in humans and is currently undergoing proof-of-concept testing. This work is being done by a consortium led by the NITD and funded by the Welcome Trust, Medicines for Malaria Venture (MMV) and the Singapore EDB. Even if these tests are successful, the route to regulatory approval could take up to eight years. The program, however, exemplifies the ongoing commitment of Novartis to remain the pharmaceutical leader in the fight against malaria.