gms | German Medical Science

The recent partnership between Merck Serono, the pharmaceutical branch of Merck KGaA, and Medicines for Malaria Venture (MMV), a non-for-profit organization, focuses on a drug discovery program aiming at developing new anti-malarial compounds with long duration characteristics. With the increasing threat of emerging resistance to current anti-malarial treatments, it is critical to expand the variety of new therapeutic options. This includes compounds providing long term protection to reduce the potential of re-infection and allowing for treatment combination to decrease the risk for triggering resistance mechanisms. This is currently a major gap in the target compound profiles being currently explored by various organizations.

Mefloquine (Lariam^®) remains today the standard long duration treatment, with a half-life of a few weeks, however its severe CNS side effects highlights the need for the development of a therapeutic alternative. A new chemical class has recently been discovered at Merck Serono that presents key characteristics to fill this gap. This carbazole derivative series has in vitro efficacy on blood stage P. falciparum (NF54) in the nanomolar range. The lead compound is metabolically stable in rodents and humans, allowing for an extended PK profile in mice with a t_1/2 life >100 hrs. It provides complete remission in the P. berghei mice model and a slow paracitocidal onset in immunosuppressed P. falciparum infected mice, without recrudescence 60 days after infection. Additionally, it shows in vitro efficacy on an extended panel of P. falciparum strains presenting various degree of resistance to current anti-malarial treatments.

Although the program is still in its early phase, the overall profile of this series is very promising and may fill the gap in long-duration, safe anti-malarial treatments. Finally, it is noteworthy that the particular set-up of the Merck Serono-MMV partnership, where the project team is composed of members from both organizations and the resources and networks are shared, is a clear example of an innovative partnership between a pharmaceutical company and a not-for-profit organization allowing for an efficient and truly integrated program.