DSM265 is a triazolopyrimidine-based highly selective inhibitor of Plasmodium’s dihydroorotate dehydrogenase (DHODH), a key enzyme for the parasite’s survival. In January 2015, the compound entered a phase IIa clinical trial in Iquitos, Peru. Here, its activity in both P. falciparum and P. vivax malaria patients is being put to the test. Preliminary results from the trial are very encouraging.
In parallel, the potential of DSM265 as a novel chemopreventive agent is being assessed in two experimentally-induced infection studies, in collaboration with Prof. Peter Kremsner in Germany1 and Dr Jim Kublin in the USA.2 The compound is being progressed in collaboration with Takeda Pharmaceutical Company, Japan.3
Dr Martin Casapia Asociación Civil Selva Amazónica (ACSA), Iquitos, Peru; Co-Investigator for the DSM265 phase IIa trial tells us more.
1. What is the burden of malaria and its impact in Peru?
In Peru, there are around 50,000 malaria cases a year, mostly in the jungle, where it is endemic. We have both P. vivax and P. falciparum malaria, but much more P. vivax – around 70–80%. It has a big impact, as morbidity is very high. Patients are not able to work or perform their regular activities when they are suffering. They lose many days of work and many of them suffer repeatedly. People usually have infection several times per year; in many cases five times a year or even as much as 10 or 20 times.
2. What is the current treatment in Peru and how do patients react to the regimen?
Treatment for P. vivax is chloroquine+ primaquine and for P. falciparum its artesunate+mefloquine. Adherence is definitely a problem, more so for P. vivax than P. falciparum. Primaquine for P. vivax should be taken for 7 days, but patients often take the treatment for 3 days and no more. The reason is that patients get much better quickly and then don’t want to take more pills. They might feel it’s dangerous to take pills for lots of days. Nevertheless, we do work hard to encourage compliance.
3. What would be the ideal antimalarial medicine for Peru?
An ideal medicine would be a short treatment course. A treatment that could be taken in just one pill would be the best.
4. What is unique about DSM265?
From the phase I data it looks like it may have potential to be part of a singleexposure treatment. So if this is proven, it would be a good alternative for our patients, especially here in Iquitos where adherence is an issue.
5. What is special about this study?
It’s been very interesting to work with a new drug. It’s a challenging and complex study, but I have been impressed with the accomplishment of the team. When the weather conditions allow, recruitment in general is not a problem and people are usually happy to participate in the study because malaria is a big problem here and by being part of the trial they know they will receive treatment. Also, we have established a good working relationship with the community.
1. With support from the German Center for Infection Research (DZIF).
2. With support from the United States Department of Defense.
3. With support from the Global Health Innovation Technology (GHIT) Fund.