Novel malaria drug clears parasitemia in phase 2 study

Novel malaria drug clears parasitemia in phase 2 study

1. KAE609, a novel spiroindolone class drug, was shown to have rapid antimalarial activity in this phase 2, open-label trial conducted in 21 patients.

2. While there were 7 adverse events attributed to the study drug, none of these led to the discontinuation of KAE609.

Evidence Rating Level: 4 (Below Average)

Study Rundown: Over the past 20 years, significant advances have been made in controlling malaria and reducing mortality. Twenty years ago, the treatment of malaria was limited to the use of chloroquine, which had initially been very successful, though later succumbed to widespread resistance. The development of artemisinin-based therapies for malaria in the 1980s and subsequent mass production in the 1990s was a key factor in the effort to combat malaria, helping to reduce absolute global mortality from malaria by about one-third over the past two decades. The advent of artemisinin-resistant malaria, however, is a growing concern and may be a barrier to making further gains in malaria control. A program to develop novel antimalarial medications has been active over the past two decades, and several promising candidate drugs are currently being studied.

This phase 2, open-label study assessed the efficacy and safety of KAE609, a new spiroindolone medication that targets parasite plasma membrane Na+-ATPase. In summary, KAE609 was found to be effective in rapidly clearing parasitemia in 21 patients with Plasmodium vivax and falciparum infections. The median time to parasite clearance was 12 hours, with parasite clearance half-life of 0.95 hours in the P. vivax group and 0.90 hours in the P. falciparum group. No adverse events led to the discontinuation of the study drug. While these results are promising, larger studies are needed to formulate conclusions about the efficacy and safety of KAE609.

Click to read the study, published today in NEJM

Click to read an accompanying editorial in NEJM

Relevant Reading: Effectiveness of antimalarial drugs

In-Depth [phase 2, open-label study]: This study explored the parasite clearance and safety of KAE609 at a dose of 30 mg daily for 3 days. The trial was conducted at three hospitals in Thailand. Patients were eligible for the study if they were between 20-60 years of age, weighed between 40-90 kg, had fever or a history of fever, and had microscopy-confirmed P. vivax or P. falciparum monoinfection with asexual-stage parasite counts between 5000-50,000/mm3 of blood. Patients were excluded if they had severe malaria according to 2010 World Health Organization guidelines, infection by multiple species, a hemoglobin less than 10.0 g/dL, schizontemia, severe vomiting, received any antimalarial agent in the 14 days prior to enrolment or any investigational drugs in the 30 days prior, a history of significant electrocardiographic abnormality, or a history of cancer, chronic liver disease, or severe malnutrition.

A total of 21 patients were enrolled in the trial–10 with P. vivax and 11 with P. falciparum. In both cohorts, the median parasite clearance time was 12 hours (IQR, 8-16 hours in the P. vivax group, 10-16 hours in the P. falciparum group). The median parasite clearance half-life was 0.95 hours (IQR, 0.85-1.14 hours) and 0.90 hours (IQR, 0.78-1.07 hours) in the P. vivax and P. falciparum groups, respectively. A total of 14 adverse events were noted during the study, with 7 of them being attributed to the study drug. These events included elevated aminotransferase levels in 2 patients, anorexia, muscular pain, and abdominal pain. No adverse event led to the discontinuation of the study drug.

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