Alternative malaria medicines

Dr Isabelle Borghini-Fuhrer
Dr Isabelle Borghini-Fuhrer Director, Product Development, MMV

Prevalent in Southeast Asia, South America and some African regions, the malaria parasite Plasmodium vivax has historically been considered relatively benign compared to the deadly P. falciparum. However, this species is becoming increasingly resistant to the antimalarial drugs currently on the market and certainly represents a major threat to global public health.

Treatments capable of suppressing these resurgent malaria attacks in patients infected by P. vivax are available, but, owing to genetic incompatibilities, current medicines are not suitable for every affected individual. Dr Isabelle Borghini-Fuhrer, Clinical Development Director at the MMV voices the urgent need to develop new medications for malaria in general and explains, in this special issue of International Innovation, how MMV and partners are working to develop Pyramax®, a combination treatment of two antimalarial drugs that is soon to be launched in several malaria-endemic countries as a new therapy.

1. Can you outline the methodology of your investigation into the relative efficacy of oral pyronaridine-artesunate (Pyramax®) versus chloroquine?

Medicines for Malaria Venture (MMV), Shin Poong Pharmaceutical Co Ltd and researchers from the University of Iowa, USA, collaborated on the clinical trials for Pyramax®. They carried out a clinical trial in 456 patients with Plasmodium vivax malaria in five hospitals across Cambodia, Thailand, India and Indonesia, comparing it with the standard chloroquine treatment. The patients were allocated treatments in a random manner. They stayed hospitalised for the first three days of the trial and their clinical condition, their malaria symptoms and the parasites in their blood were monitored carefully and frequently. Once the symptoms resolved and the parasites were cleared, the patients were discharged. They were asked to return to the clinic for follow-up visits for the next six weeks, during which their clinical condition and blood were assessed. This was to ensure that the malarial parasites had not reappeared once the patients were cured, and to monitor all the safety parameters and any potential adverse side-effects. One month after the study started, patients were also treated with primaquine to eliminate any dormant forms of the P. vivax parasite intheir livers.

2. What were the results of this study?

The results showed a very high efficacy of the combination therapy Pyramax® to treat acute P. vivax malaria. The cure rate was very high (99.5 per cent at day 14) and was demonstrated to be statistically non-inferior compared to that of chloroquine throughout the 42 days of follow-up. The results also showed that Pyramax® acted very fast, with parasite and fever clearance time significantly shorter than with chloroquine; patients also felt better faster. Importantly, the risk of recurring malaria infection during follow-up was reduced considerably in the group treated with Pyramax® when compared with the group treated with chloroquine.

3. Are side-effects an important factor to consider when examining the relative usefulness of these different drugs for widespread clinical use?

Clinical development programmes for malaria usually involve around 2,000 patients and give a good idea of the side-effect profile; and, therefore, of the risk/benefit ratio. Once the product is on the market and widely used, the side-effect profile continues to be collected and analysed in post-marketing pharmacovigilance studies, where safety data are collected for a much larger group of patients.

4. Does a mixed infection of P. falciparum and P. vivax present additional complications when treating malaria?

Mixed infections need drugs that are effective at getting rid of both parasite species. Not all drugs have this ability (eg. sulfadoxine-pyrimethamine, which works for P. falciparum but not P. vivax).In areas of the world where both species coexist and health systems are lacking in resources, diagnostic tests that distinguish between the two species are not always available. In these cases, once patients are diagnosed with malaria, it is important to treat them with drugs that are effective against both malaria strains.

5. Malaria is a truly global disease; how does collaboration within this programme help to combat it?

No single organisation can tackle malaria alone, as it is a disease of immense complexity and spread, largely afflicting the poorest and most vulnerable populations. Over its 14 years of existence, MMV has built a worldwide network of over 300 equally enthusiastic partners in 50 countries, committed to a malaria-free world and to accelerating and reducing the cost of developing much-needed antimalarials. Currently, 150 of these partners are working on MMV’s pipeline of over 65 antimalarial projects, of which Pyramax® is one. For this programme, we consulted expert malariologists from malaria-endemic countries who are best placed to define unmet medical needs. They advised us on clinical trial design, feasibility and conduct.

6. What does the future hold for antimalarial medication? Will an increased understanding of the molecular and genetic basis of malaria infection yield advanced ways of preventing and treating the disease?

Certainly a better understanding of the parasite’s biology will allow scientists to target therapies to specific steps in its life cycle. Ultimately, it will allow us to conduct intensive surveillance to track and delay the spread of resistant parasites; and accelerate the development of new drugs to counter it.

Go to the interview in International Innovation's special edition on malaria.