An experimental Novartis AG medicine that killed drug-resistant malaria in laboratory studies may become the first new class of treatment against the disease in 30 years, researchers said.
The drug cured mice at lower doses than existing medicines and killed drug-resistant strains taken from patients in Thailand, researchers said in the journal Science yesterday. Human trials of the drug are planned for this year.
“I would be extremely shocked if someone comes back and tells me that we’re not hitting the bug in humans,” said Thierry Diagana, who led the research at the Novartis Institute of Tropical Diseases in Singapore. “When I see the type of potency that we’re getting, I’m very excited and very optimistic,” Diagana said in an interview.
Researchers are hunting for new treatments against malaria after a study last year showed drugs derived from artemisinin, the basis of the most effective medicines, were losing power in Cambodia, jeopardizing global efforts to curb the spread of the malady. The Novartis drug would be the first to work in a new way since the first artemisinin-based drugs were developed in the 1970s, according to Diagana.
Malaria infects about 250 million people each year and kills more than 880,000, mostly children under 5 in Africa, according to the World Health Organization. It’s the world’s third-deadliest infectious disease behind AIDS and tuberculosis.
Ancient Chinese Remedy
Artemisinin is an ancient Chinese remedy derived from the leaves of the sweet wormwood tree. A study published in the New England Journal of Medicine last year showed drugs derived from artemisinin took almost twice as long to clear the parasites that cause the disease in patients in western Cambodia as in patients in northwestern Thailand.
While Cambodia accounts for only about 0.4 percent of the world’s malaria cases, it’s a breeding ground for drug-resistant strains. Since the 1970s, at least three once-potent malaria treatments have failed there before becoming useless elsewhere in the world, according to the WHO.
New drugs developed over the past 30 years have been variations on previous treatments, leaving them vulnerable to the same weaknesses as their predecessors, Diagana said. Novartis’s medicine targets the parasite in a way it hasn’t seen before and isn’t resistant to.
The drug is the result of more than three years of work by almost 30 scientists in five countries. Researchers at a Novartis lab in San Diego sifted through 12,000 chemical compounds starting in 2006, finding 275 that had an impact on the deadliest species of the parasite that causes malaria, according to the study.
They then discarded those that didn’t work against resistant strains or were considered too toxic, whittling the contenders down to 17. Among those, they identified one family of chemicals, called spiroindolones, as the most promising.
Chemists at Diagana’s lab in Singapore then developed about 200 variations of the compound, eventually settling on one called NITD609 that could be mass-produced as a daily pill.
Diagana and colleagues tested it at three doses against four approved malaria drugs in infected mice. At the highest dose NITD609 cleared the parasite from all the animals treated with it. None of the mice tested with the same dose of other drugs was cured.
It also worked against strains of the disease taken from patients on the Thai-Myanmar border, where resistance to chloroquine, an older treatment, has been observed. The researchers plan to test the drug against artemisinin-resistant strains as soon as samples become available, Diagana said.
The study is “very exciting work,” said Nick White, a professor of tropical medicine at the Mahidol Oxford Tropical Medicine Research Unit in Bangkok who studies drug-resistant malaria. “These could be a promising new class of antimalarials,” he said in an e-mail.
The research was funded by Novartis, the Wellcome Trust, the Medicines for Malaria Venture, and the U.S. and Singapore governments.
“Can NITD609 replace artemisinin? Unfortunately, as in most drug development, the answer is ‘wait and see’,” Timothy Wells, chief scientific officer at the Geneva-based Medicines for Malaria Venture, wrote in an editorial accompanying the study. “The speed at which NITD609 has moved from a hit to a preclinical drug candidate, however, suggests that we may not have to wait too long.”