Studies show single-dose potential for new malaria drug

Two human challenge studies on a new malaria drug called DSM265 yielded promising data about safety and dosage and how the drug might fit in to strategies to prevent and treat infections, a pair of research groups reported yesterday.

The studies—one by an international team and the other by a group based in Germany—appeared in The Lancet Infectious Diseases. Over the past 15 years, malaria levels have steeply dropped, but resistance to first-line drugs is threatening progress toward eliminating the disease.

Among several new drugs being studied, DSM265—which blocks a key Plasmodium biosynthesis enzyme—is one of the few long-acting new antimalarials in clinical trials. The drug was discovered using throughput screening by researchers from the University of Texas Southwestern, the University of Washington, and Monash University. It is being developed by the Medicines for Malaria Venture (MMV) and Takeda Pharmaceuticals.

Studies included treatment potential

Experiments by both groups used a controlled human malaria infection (CHMI) model, designed to allow molecule activity to be tested in volunteers treated with a low dose of malaria parasites in a tightly controlled clinical trial setting.

The study by the international team, which included researchers from MMV, is an integrated phase 1a and 1b trial to explore not only safety and tolerability, but also treatment potential. It used a "blood stage" CHMI model.

DSM265 had a good safety profile, with pharmacokinetic markers showing a long half-life, with plasma concentrations above the Plasmodium falciparum minimum inhibitory concentration for more than 8 days, suggesting that the drug might be useful as a single dose when combined with another medication, which could streamline treatment and lead to better compliance.

The information from the study was used to design a phase 2 study involving malaria patients in Peru, which has already been completed, with results published soon.

Meanwhile, the group based at the University of Tubingen in Germany explored the prophylactic potential of a single DSM265 dose using a "sporozoite" CHMI model.

Those investigators found that a single 400-milligram dose was well tolerated and showed prophylactic activity when given 1 day before experimental infection. Efficacy was lower when the drug was given 7 days before infection, but DSM265 maintained partial protection against the asexual blood stage of the parasite.

Promising prospects for future use

In a commentary in the same Lancet Infectious Diseases issue, Elizabeth Ashley, MD, with the Myanmar Oxford Clinical Research Unit in Yangon, wrote that taken together, the two studies suggest that DSM265 is a medium-potency, slowly eliminated, well-tolerated antimalarial.

She added, "If these results are confirmed in acute malaria then it would be a suitable partner drug used in combination with a more rapidly effective agent for malaria treatment." She added that safety and efficacy information is still needed for larger numbers of patients who have naturally acquired infections and against illnesses involving non-falciparum species.

The relatively short protection period makes it unlikely to be used as prevention for pregnant women and children in endemic area, but if the dose can be optimized to allow weekly use, she wrote, it might be a candidate for travelers, possibly replacing mefloquine.

"Investment in the antimalarial pipeline is finally bearing fruit," Ashley said, crediting a development model that involves collaboration between public and private sectors.

David Reddy, PhD, chief executive officer of MMV, said in an MMV press release that the timing of the trials—gathering tolerability and efficacy in parallel during early development—is a first in antimalarial drug development and shows that innovative approaches can help speed up development.

"It's an exciting time to be involved in antimalarial drug research and development," he said.

See also:

Mar 28 Lancet Infect Dis abstract on study from international research team

Mar 28 Lancet Infect Dis abstract on study from German research team

Mar 28 Lancet Infect Dis commentary

Mar 29 MMV press release

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