DSM265 has the potential to both treat and protect against malaria in a single dose. The compound selectively inhibits a vital enzyme (dihydro-orotate dehydrogenase; DHODH) in the malaria parasite essential for its survival, while the human enzyme remains unaffected at and beyond therapeutic concentrations.
The compound successfully demonstrated safety and efficacy against Plasmodium falciparum in a phase IIa trial in malaria patients in Peru, and the data is expected to be published in 2017. Phase III trials in combination with a partner drug/drugs are planned to further confirm this activity.
DSM265 is being developed with Takeda Pharmaceutical Company Limited, headquartered in Japan, with funding from the Global Health Innovative Technology Fund (GHIT) and pro bono support from AbbVie.
Prof. Alejandro Llanos-Cuentas, Principal Investigator for the phase IIa study in Peru talks about the trial, the challenges of managing malaria in Peru and how DSM265 could help address them.
1. What was the biggest challenge you faced during the study and how did you overcome it?
For the people of the Amazon, malaria is not a disease considered to require hospitalization, especially as their livelihood and ability to provide for their families depends heavily on their ability to work. Originally the protocol planned for 3 days of observation of patients in the clinic following treatment, but in practice at times we needed to keep them in for longer. In these cases, it was challenging to convince them stay. To overcome this, we spent additional time explaining the situation and the importance of the study to patients and their families and where necessary provided them with housing and food.
2. What are the main challenges in managing malaria in Peru?
Recently, there has been a resurgence of both Plasmodium vivax and P. falciparum malaria in Peru. Between 2005 and 2011, a malaria control programme was implemented with economic support from the Global Fund, which led to an 80% decrease in cases (11,000 cases were reported in 2011). However, 2 years later in 2013, the number increased to around 40,000 and then to 60,000 in 2014. Unfortunately, these increases are no longer the exception but the rule.
The causes range from lack of adequate antimalarial medicines and a lack of knowledge, as well as competing government priorities leading to inaction. Through studies conducted by our group in recent years in the Peruvian Amazon, we find we have a large number
of people with asymptomatic1 or subpatent2 malaria, who carry the disease but are themselves not sick and so don’t seek treatment. This mass of people act as a reservoir for the transmission of infection and are a serious challenge to malaria elimination since they are difficult to identify, diagnose and treat.
3. What is exciting about DSM265 as a future antimalarial, particularly in the Peruvian context?
In combination with another medicine, DSM265 could be an excellent prospect for both asymptomatic and subpatent P. falciparum malaria because it could potentially be used as a single dose. This would be a key tool to eliminate malaria in endemic regions like the Amazon.
4. What was it like working with MMV on this study?
The experience was very good. MMV and its people have a genuine concern to find new therapeutic solutions for malaria.
- People with asymptomatic malaria carry a low level of malaria parasites, as confirmed by thick blood smear test using optical microscopy, but don’t have any symptoms.
- People with subpatent malaria infections carry an even lower level of malaria parasites, they test negative for malaria via a rapid diagnostic test and thick blood smear but positive by polymerase chain reaction.