• Mefloquine analogs: an in vitro assay to predict neurotoxicity has been established, in order to identify several potent mefloquine analogs which do not have in vitro neurotoxic effects.

• Tafenoquine: Phase 2 studies have been completed in partnership with GlaxoSmithKline Pharmaceuticals. This product has a very long half-life, and may be effective for prophylaxis when taken monthly.

• Azithromycin/chloroquine and azithromycin/quinine: these combinations are known to be safe and effective in children and in pregnant women. Pfizer Pharmaceuticals is collaborating with WRAIR in clinical trials in Thailand and Kenya.

Given the remarkably limited resources, the progress in antimalarial drug development over the past 5 years or so has been impressive. Direct expenditures total less than US$50 million in 2004, even including a large proportion of in-kind expenditures. For most of the products in development, however, the costliest phases—clinical trials—are yet to come. The global community must plan to increase funding resources for the core groups, MMV and WRAIR (mainly the responsibility of the U.S. government). As more projects mature beyond early development, the pharmaceutical industry also will need to step up in-kind contributions in the developmental areas it does best.

It is not a useful exercise to compare expenditures on antimalarial R&D to commercial drug development (which totals some hundreds of millions of dollars per successful product), but something of the scale should be kept in mind when global investments in antimalarials are considered. During the course of this study, the committee did not independently calculate an “appropriate” amount of investment in antimalarial R&D, but has concluded that current levels are less than optimal, and that increased funds will definitely be required merely to maintain the momentum of existing development activities. MMV, which manages about half the antimalarial R&D worldwide, has estimated its needs at US$30 million per year for development and early clinical studies (Personal communication, R. Ridley, WHO, March 2004). As compounds progress through to advanced clinical and field trials, at least an additional US$10 million per year will be needed (this also assumes continuing contributions in kind from industrial partners not included in these figures). The recently established European and Developing Countries Clinical Trials Partnership (whose funding goal over the next five years is 600 million Euros, including 200 million from the founding European Commission (European Union, 2004) could play a key role in this phase. Equal amounts totaling US$30 million per year plus extra funding for clinical trials and industry investments will be needed for the WRAIR program to remain productive.