Death from severe falciparum malaria varies from 10-40% depending upon the time of starting treatment and the facilities for management of its complications. The disease can progress so rapidly that, for a patient who can no longer take oral drugs, survival depends upon the speed of reaching facilities where parenteral drugs can be given. When such facilities are distant from the patient's home, death may occur within the first 96 hours after admission to hospital.
Artesunate, a water-soluble semi-synthetic hemisuccinate derivative of artemisinin, has a clinical performance which is arguably one of the best documented in areas of multi-drug resistance. In theory, Rectocaps , a suppository formulation of artesunate manufactured by a Swiss Company, Mepha, is promising as it offers the prospect of providing safe and effective treatment for severe malaria in rural areas of the tropics where parenteral drugs cannot be given. No other antimalarial drug has been registered for use at an early point in the evolution to severe disease. It does not cure the disease (i.e. eliminate parasitaemia) but it can save lives by providing therapeutic cover en route to hospital. Within hours the drug can reduce parasitaemia, and the patient rapidly returns to per os' status. The onset of complications and the associated hospital admissions are thereby prevented, and mortality caused by acute Plasmodium falciparum malaria is significantly reduced. Children and infants are the main beneficiaries of the formulation; they are the most at risk of early death. Other advantages are that the formulation is unlikely to be abused and can be given by minimally trained personnel. The benefits are: lives saved, avoidance of severe disease and a reduction in the acute case load (and associated costs) at peripheral hospitals.
During the past year, TDR's Task Force on Artesunate Suppositories has initiated rigorously controlled clinical trials to examine the potential of the product for a strictly limited indication: for patients unable to take oral drugs en route to hospital where normal parenteral treatment can be instituted. Phase II trials have been implemented in patients with moderately severe malaria in Asia and Africa. The purpose of these trials is to examine the pharmacokinetic parameters and the safety, tolerance and clinical efficacy of the product in comparison with parenteral administration and to establish the acute bioavailability of artesunate in patients. The results, although not yet fully analysed, provide an optimistic view of the drug. Phase IIb trials are now in progress and TDR will soon initiate large-scale field studies on three continents.
In taking this initiative, TDR has utilized its unique position to bring to the drug development process the highest level of expertise - seconding expertise from regulatory agencies (in Europe, North America and Africa) as well as international expertise in severe malaria, clinical pharmacology and epidemiology. This is in addition to the collaboration between the three main partners (the Company, the regulatory bodies, and the researchers). Using this new approach to drug development, a workplan has been articulated which removes all defensive research in the pursuit of the objective: to develop a life-saving intervention for a major, neglected disease.