Several earlier phase drug discovery activities funded by MMV also are under way. Thus, entirely new classes of antimalarials may start to come on to the market soon after 2010.

Several enhanced formulations of existing drugs also are under development.

  • Paediatric Coartem formulation by Novartis in collaboration with MMV, and TDR (MMV funded).

  • Rectal artesunate, developed by WHO/TDR, for use as a single administration for malaria patients unable to take antimalarial medication by mouth, before they are referred for hospital treatment.

  • Artesunate i.v. formulation for severe malaria; a collaboration between WRAIR, and MMV.

WRAIR has its own suite of new antimalarial drugs. Several families of compounds have progressed into preclinical development, including:

  • Pyrroloquinazolines: new analogs that show none of the toxicity common to the parent drug, and yet retain oral potency against highly resistant malaria in animal studies. Should enter clinical studies in 2005.

  • Third generation anti-folates: these show no cross-resistance in studies against multidrug resistant P. falciparum. They are under development in collaboration with Jacobus Pharmaceuticals.

  • Imidazolinedione derivatives: these compounds are unique in that they specifically kill liver stages of malaria but have no activity against blood stages. Because they are not in the 8-aminoquinolone drug class, they are not expected to create hemolysis in G6PD-deficient people. May enter clinical studies in 2005.

  • Tryptanthrins: a well-known, extremely potent class of chemicals with in vitro activity against trypanosomiasis as well as malaria. Difficulties with oral bioavailability have historically impaired progress with this drug class.

  • New macrolides: azithromycin nearly meets criteria as an effective malaria prophylactic drug. Many analogs have been identified with superior in vitro potency against multidrug-resistant malaria. PLIVA Pharmaceuticals is collaborating with WRAIR to develop these new analogs.

  • Chalcones: WRAIR is just beginning assessments of this drug class in collaboration with LICA Pharmaceuticals.

  • Methylene blue: this compound very rapidly kills malaria in animal studies, and appears to be nontoxic at effective doses. It may be a good partner for a combination antimalarial regimen. Its potential utility in malaria prophylaxis still being explored.

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