Drug Proves Able to Cure Disease Borne by Parasite

By KENNETH CHANG

drug originally developed to combat breast cancer has instead proved effective against a parasitic disease that kills tens of thousands of people each year, many of them in northeastern India, researchers reported today.

Confirming earlier, smaller studies, an international team of researchers has found the drug miltefosine (pronounced mill-TEFF-oh-seen), a pill that can be taken orally, cured the disease, visceral leishmaniasis, 94 percent of the time. They report their findings in today's issue of The New England Journal of Medicine.

About half a million people worldwide are infected annually with visceral leishmaniasis (pronounced leesh-ma-NIGH-a-sis, also known as kala azar or black fever), with about half of the cases in India. The disease is transmitted via the bites of sandflies, which inject the parasite leishmania donovani into the body. In visceral leishmaniasis, the most serious form of leishmaniasis, the parasites take up residence in the liver, spleen and bone marrow, inducing fever and malaise. Untreated, it kills within a couple of years.

The disease was already treatable, but the treatment involved a month's hospital stay and daily injections, putting it out of reach for most victims of the disease. In India, the disease is most prevalent in Bihar. It also strikes hard in neighboring Nepal and Bangladesh.

"This disease hits the poor, and the treatment cost is very high," said Dr. Shyam Sundar, a professor of medicine at Benares Hindu University in India and lead author of the study. "The capacity to treat these patients in hospitals is limited. So many patients go untreated, and they die."

The miltefosine treatment — one or two pills a day for 28 days — does not require hospitalization. Dr. Sundar said he hoped that the pills would become available at cost of about $50 for a month's supply. "Unless it's affordable, there's no point in it being available," he said.

Dr. Robert Ridley, who coordinates product research and development at the World Health Organization's tropical disease research program, said miltefosine could prove an important tool in controlling the disease and lowering the number of deaths. "It's the first time we've had a drug that can be orally administrated to treat visceral leishmaniasis," he said.

The maker of miltefosine, Zentaris of Germany, is in talks with the Indian government and the World Health Organization on how to make the drug available at an affordable cost. "We are working on it heavily," said Dr. Mathias Pietras, head of marketing and communication for Zentaris.

Dr. Ridley said, "I would envisage early on in the coming year that all issues would have been sorted out."

In the study, 299 patients with moderate leishmaniasis took miltefosine while 99 others received injections of the drug amphotericin B, the current treatment. At the end of the treatment, no signs of the parasite were found in either group.

Six months later, several in the miltefosine group suffered relapses, leaving a 94 percent cure rate. The cure rate for amphotericin B was 97 percent.

Miltefosine was discovered by German scientists in the mid-1980's and looked promising against breast cancer, but gastrointestinal side effects in clinical trials derailed its chances. A topical form of the drug has been developed to treat skin lesions from the spread of breast cancer.

In the lower doses used to treat leishmaniasis, side effects have not been severe. Nearly 40 percent of the patients taking miltefosine suffered some vomiting and 20 percent suffered diarrhea, but the symptoms generally lasted only one or two days. "Not a big deal," Dr. Sundar said. "Most patients tolerated it very well."

Additional studies will examine practical considerations such as the distribution policies to ensure that pregnant women do not take miltefosine. Animal studies indicate the drug might damage a fetus.

"These sorts of operational issues are the sorts of things being looked at," Dr. Ridley said. "Everyone is very enthusiastic about the prospects."

Other studies will look at whether the drug is also effective against strains of leishmaniasis in Africa and South America. The disease has also spread more widely into southern Europe in recent years.