Triple combination therapy for acute uncomplicated and severe Malaria
Hamburg, April 25, 2023
Through its proprietary interest in fosmidomycin as a novel antimalarial drug, DMG Deutsche Malaria GmbH is pursuing a strategy of triple combination therapy as an immediate response to the threat of artemisinin resistance in sub-Saharan Africa. Already there are reports of the artemisinin-base combination therapies (ACTs) becoming less effective and should full-blown resistance develop, it would have a devastating effect on vulnerable populations especially in children under five years of age.
The groundwork for this approach has already been achieved through separate studies of fosmidomycin in combi-nation with artesunate and of fosmidomycin in combination with piperaquine. In both instances, these combina-tions proved to be highly effective and well tolerated in the treatment of uncomplicated Plasmodium falciparum malaria. But these combinations, in common with the currently used ACTs, will be under pressure from the devel-opment of resistance and call for reinforcement from a third component.
Fosmidomycin, through its unique mode of action as an inhibitor of the non-mevalonate pathway, adheres to the principles of combination therapy and is therefore a strong candidate for inclusion in the existing ACTs. By enhancing the rapid response to the artemisinin derivative, most usually artesunate, a more complete reduction in the parasite biomass will be achieved resulting in a highly effective therapeutic response afforded by the prolonged action on the residual parasites by the slowly eliminated partner drug, most typically a 4-aminoquinoline of which piperaquine is an example.
The rationale for the choice of fosmidomycin in the setting of a triple combination has been substantiated by a study conducted under the auspices of the Bernhard-Nocht-Institute for Tropical Medicine in Hamburg and the Institute for Tropical Medicine in Tübingen and funded by the German Center for Infection Research (DZIF). Fosmidomycin was combined with clindamycin and artesunate for evaluation in the treatment of acute uncomplicated Plasmodium falciparum malaria in a study undertaken at the Kumasi Center for Collaborative Research in Ghana and at the Centre de Recherches Médicales de Lambaréné (CERMEL). Again, in common with the two studies referred to above, the response was dramatic with the achievement of a cure rate in excess of 95%. However, caution should be exercised in promoting the use of this triple combination for uncomplicated malaria by reason of the risk of inducing bacterial resistance as a consequence of fosmidomycin and clindamycin possessing dual activity against bacteria and malaria parasites. Nevertheless, such dual activity coupled with artesunate underlines the rationale for the development of this triple combination as an advance in the treatment of severe malaria, a development which has the support of the malaria community as it addresses coexisting bacterial infections.
With initial support from the EU Malaria Fund, the Company is committed to this endeavour although progression to clinical trials is dependent on the outcome of a separate grant application and other funding sources as they become available.
Investment in the Company is key to embarking on the development of a triple combination for uncomplicated ma-laria and it is the intention of this press release, timed to coincide with World Malaria Day 2023, that it should serve as an invitation to investors to participate in such a worthwhile enterprise.
Enquiries should be addressed to Dr David Hutchinson, Managing Director, DMG Deutsche Malaria GmbH at: d[email protected]