About the Portfolio

Too many ACTs?
People often ask us whether so many new ACTs are excessive for malaria, and whether one would suffice. The answer is a resounding ‘No’. The risk of attrition in drug development is high, as shown by the Dacart study results, and reliance on just one or two new drugs in development for malaria is imprudent. Already in our clinical studies we see dissimilarities in the way the disease responds to different medicines. As we move into 2008, we will start more clinical studies in specific patient groups: small children, expectant mothers, and patients who not only have malaria but have AIDS or tuberculosis. It is here that the choice of different medications will be crucial to the optimal treatment of malaria. No one medicine alone can be expected to be the best for all the different groups of patients we have, and for all the different parts of the world that are affected by malaria.

The Future
Furthermore, we are expanding the indication of our antimalarial drugs to go beyond treatment, to actually prevent malaria infections in infants. Our partnerships with clinical consortia such as the intermittent preventative treatment in infants ( IPTi ), Malaria in Pregnancy ( MiP ) and Phase IV Consortium, will become increasingly important over the next few years. In addition, as MMV continues to expand its work in access to antimalarials by vulnerable populations, it is critical that we get the science right. The drugs we develop are specifically tailored to patient needs, with the ultimate goal of a one-dose cure.

Drug resistance
Drug resistance constitutes the major threat to malaria control today (see chart to right). Resistance to chloroquine was first recognized more than 40 years ago in South America and South-East Asia, and in 1979 was first reported in sub-Saharan Africa, where 90% of global malaria mortality occurs. Emergence and spread of drug resistance reduces the useful therapeutic life of drugs, and has devastating effects on malaria control efforts.

The drug being used most often today in combinations is artemisinin
Artemisinin drugs first introduced in South-East Asia a little over a decade ago have proven to be well tolerated and the most potent of antimalarials. They exhibit the following properties:
  rapid significant reduction of parasite biomass
  rapid resolution of clinical symptoms
  effective against multidrug resistant P.falciparum
  reduction of gametocyte carriage, which may reduce transmission.

However, artemisinin drugs have a very short half-life and thus a multiple dose regimen of seven days is required to achieve an acceptable cure rate. When artemisinins are used as monotherapy, recrudescence of malaria is common.

Combining an artemisinin drug with a partner drug that has a longer half-life improves the efficacy of the artemisinin. It also reduces treatment duration with the artemisinin and the likelihood of development of resistance to the partner drug. Artemisinin-based combination therapy (ACT) has already been shown to improve treatment efficacy and contain drug resistance in South-East Asia, and to date there is no evidence of parasite resistance to artemisinins.

Artemisinin (qinghaosu), artesunate, artemether and dihydroartemisinin have all been used in combination with other drugs for the treatment of malaria. MMV has included two fixed combinations of artesunate with other known antimalarials (chlorproquanil-dapsone artesunate and pyronaridine artesunate) in its portfolio.

Assuring a reliable supply of ACTs has been a major concern in recent years and the World Health Organization and other global players are currently seeking long-term solutions.

See also:

  MMV Strategic Consultation Position Paper
Selection of Partners for Antimalarial Drug Combinations
based on meeting held on 29 January 2005 in Geneva, Switzerland
  Download paper (PDF) (185KB)