Reuters Health Information: Novartis drug clears malaria parasite in phase II study
Novartis drug clears malaria parasite in phase II study
Last Updated: 2014-07-30
By Gene Emery
NEW YORK (Reuters Health) - A phase II trial of an
experimental malaria drug given once a day found that it rapidly
cleared the parasite from the blood within 12 hours, with mild
nausea being the most common side effect.
The test, reported in the New England Journal of Medicine,
comes at a time when doctors are desperately searching for a new
weapon in their fight against a disease that kills roughly
627,000 people worldwide each year and has been showing
increasing resistance to established therapy.
The experimental drug, developed by Novartis, is designated
KAE609 and was formerly known as NITD609. The company financed
"This is rare good news in malaria treatment and
prevention," said Dr. Christopher V. Plowe, leader of the
Malaria Group at the Center for Vaccine Development at the
University of Maryland School of Medicine in Baltimore. He was
not involved in the study but has served as a paid consultant to
Novartis on development of the drug.
Research published in 2013 showed that the drug kills the
parasites by disabling their molecular pump for removing excess
salt. The organism, which lives in red blood cells, dies from a
The open-label test in Thailand, conducted in the first half
of 2012, involved 21 volunteers who received 30 mg of the drug
each day for three days. The patients ranged in age from 21 to
46. Only one was female, because women with childbearing
potential were not eligible.
The median clearance time was 12 hours. The interquartile
range was 8 to 16 hours for the 10 people infected with
Plasmodium vivax and 10 to 16 hours for the 11 with P.
And while fewer than 1% of a group of 5,076 patients with P.
falciparum who were treated with oral artesunate had a parasite
clearance half-life of less than one hour, half the people
receiving KAE609 had a comparable removal time.
"We were surprised how quickly the parasitemia was cleared,"
Dr. Nicholas White of Mahidol University, chief author of the
team, told Reuters Health in a phone call from Bangkok.
Fourteen of the 21 volunteers reported some type of adverse
event. Nausea was the most commonly reported adverse effect, but
its severity was assessed as grade 2 in only one patient.
"This study was too small for us to derive valid conclusions
regarding safety and efficacy," the White team concluded.
"One patient withdrew but nobody was unable to take it,"
said Dr. White. Three patients vomited, but "vomiting is quite
common if you have malaria."
Three patients had elevated liver enzymes, the authors said.
They wrote, "Elevated aminotransferase levels may also occur in
patients with acute malaria, so much larger studies will be
necessary to assess fully the safety and adverse-event profile
of this new antimalarial agent."
Studies underway now are designed to find the correct dose,
Dr. White reported.
"The way we hope we will develop antimalaria drugs in the
future will be to spend some time getting the dose right,
because in the past we tended to introduce the drug at a dose
that was too low, so that tended to induce resistance," Dr.
White said. "Once we get the dose right, we will partner it with
one or more other antimalarial drugs in the hopes that it will
eventually be used as a fixed-dose combination drug, like we
treat tuberculosis, HIV and malaria now."
A companion study in the Journal, in which Dr. Plowe is a
coauthor, illustrates how artemisinin-resistant malaria has
spread to eastern Myanmar, western Cambodia, western Thailand
and southern Vietnam. Such resistance is also appearing in
northeastern Cambodia and southern Laos.
The researchers found that standard three-day treatments
were failing but longer, six-day treatments with a combination
regimen that included artemisinin is continuing to work, with a
cure rate of 97.7%.
"We have a finger in the dike at this point against
drug-resistant malaria in Southeast Asia," Dr. Plowe told
Reuters Health by phone. "But I don't think we have very much
time and don't have good options in hand."
"We can extend the course of treatment as we've done with
this study. That may provide answers to what we can do to treat
malaria until these new drugs come online," he said.
SOURCES: http://bit.ly/WIUC7j and http://bit.ly/1zoCuxp
N Engl J Med 2014.