assistance from WHO/TDR, and WHO-RBM an agreement has now been established between Hollekin and MMV for development to international standards. Clinical studies in progress, but further GLP preclinical work still required.
Mefloquine-artesunate, a proven combination as a non-fixed treatment regimen, is being developed as a fixed-dose combination. A consortium involving the Drugs for Neglected Diseases Initiative (DNDi), TROPIVAL (Bordeaux), and Far Manginhos of Brazil are involved with EU funding, and some WHO/TDR technical support. Phase 1 clinical studies in progress.
Amodiaquine-artesunate, another proven combination as a non-fixed treatment regimen, is in development by the same consortium as above. A commercial partner is being sought for manufacture and production. Phase 1 clinical studies in progress.
In addition to the combinations cited above, there are several new single agent drugs in development that also may ultimately be used in combination. Some of these agents may be dropped as studies progress and problems appear. Projects include:
Artemisone, a new artemisinin derivative being developed by Bayer with MMV support. Its potential advantage over existing artemisinins is lower neurotoxicity, and enhanced efficacy. This compound may be registered by 2007.
A new quinoline antimalarial, similar to amodiaquine, being developed by GSK, and the University of Liverpool with support from MMV, and some technical assistance from WHO/TDR. This compound resembles amodiaquine but potentially has an improved safety profile, and is highly active against chloroquine-resistant strains. This compound may be registered by 2008.
Fosmidomycin, a new class of antimalarial, is under development by Jomaa Pharmaceuticals in Germany. This also may be used in combination with other agents. The major issue is whether it can be given as a 3-day regimen.
A new class of synthetic endoperoxide, invented at the University of Nebraska, and initially supported by WHO/TDR, is now being developed by a consortium funded and managed by MMV and is licensed to Ranbaxy of India. A compound entered into full preclinical development late in 2003. The advantage of these compounds is that they have longer half-lives than the artemisinins, and so could serve as better partners than artemisinins for longer half-life drugs. A compound in this category could be registered by 2008.