Malaria Drug May Soon Be Set for U.S. Debut

The Food and Drug Administration is expected soon to approve the first malaria drug in the United States to contain artemisinin, the wormwood derivative from China that is the latest and much heralded cure for malaria in Africa and Asia.

Although there are only about 1,500 cases of malaria treated in the country each year - virtually all in people just back from the tropics - the approval would also make the drug available to the military and to Americans planning to go abroad.

According to the Centers for Disease Control and Prevention, most of those travelers returning from the tropics with malaria had been visiting relatives in Africa, India, Haiti or Central America. About 10 percent went abroad as tourists and about 2 percent as members of the military.

The drug, Coartem, is made by the Swiss company Novartis. It combines artemether, an artemesinin derivative, with lumefantrine, a drug developed by Chinese scientists, which does not kill parasites as quickly but lingers in the blood longer.

By mopping up parasites that artemisinin misses, lumefantrine helps prevent resistance that would defeat the drug, as happened with previous so-called miracle cures like chloroquine.

Novartis saysthe F.D.A.'s legal deadline for a decision is this Friday. On Dec. 3, an F.D.A. advisory committee of independent experts voted 18 to 0 to endorse the drug's effectiveness. The agency usually takes its committees' advice.

About the expected approval, Dr. Claire Panosian, president of the American Society of Tropical Medicine and Hygiene, who treats malaria cases in Los Angeles, said: "I'm thrilled. It's a great breakthrough to have another antimalarial in the U.S."

Novartis sells Coartem (pronounced koh-AHR-tem) to the World Health Organization and medical charities for about 80 cents per course of treatment, which it says is the production cost. It has sold nearly 200 million treatments for use in Africa and claims they have saved 500,000 lives.

Coartem was introduced in 2001; it is approved in more than 80 countries, including 16 in Europe. Novartis had had little interest in registering it here because the market is so small and the food and drug agency's requirements are expensive - even when the application fee, more than $1 million for a new drug, is waived, as it was for Coartem.

Novartis came under pressure to register it here because so much taxpayer money was being spent on it after the $1.2 billion President's Malaria Initiative passed in 2005.

Because the drug is now under review, Novartis may do nothing that smacks of salesmanship to Americans. At a conference of tropical medicine doctors in New Orleans this month, the Coartem sales booth had guards preventing any United States resident from even peeking inside.

Coartem is taken only after only a patient has malaria, not for prevention.

But many safari seekers and executives stationed overseas hate the side effects of the available preventive drugs, which can vary from sun sensitivity to abdominal pain to nightmares.

Instead, suggested Dr. Bradley A. Connor, founder of Travel Health Services in Manhattan, they can carry Coartem and treat themselves if they get a fever. It is also safer when visiting countries where counterfeit drugs are common.

European travelers do this with Coartem now, and sophisticated ones will also carry a test kit that uses a finger-stick drop of blood to make sure they have malaria, because most fevers even in the tropics are something else. "Europe is way ahead of us on this," Dr. Connor said.

Registration of Coartem could also help the military, which normally cannot prescribe drugs lacking F.D.A. approval, said Col. Alan J. Magill, a doctor who is director of the experimental drugs division at the Walter Reed Army Institute of Research.

Reluctance to take malaria-prevention drugs has been regular in the military since World War II, when one side effect of atabrine was to turn users' skin yellow.

"In those days, you could say, ‘Shut up and take it, we're fighting the Japanese,' " Colonel Magill said. "The Japanese didn't have it, and they were devastated by malaria. You could make a case that atabrine won the war."

The military is still rife with rumors about such drugs, he said. In 2002, three Special Forces soldiers back to Fort Bragg from Afghanistan killed their wives, and the rumor mill blamed mefloquine, or Lariam, a powerful antimalarial that can be taken once a week but in rare cases brings on psychoses.

The following year, 43 marines who had evacuated Americans during fighting in Liberia fell ill with malaria, and blood tests showed that no one in their unit had taken all his mefloquine properly.

Colonel Magill said Coartem would not change that situation because it is not a preventive drug, but it gave military doctors more flexibility. The Special Forces, he said, already unofficially self-treat with Coartem. "They buy it off market," Colonel Magill said. "They're real smart, and with them everything is ‘mission first,' all the bureaucratic stuff later. But for the big Army, that's never going to happen."

Novartis will lose money on Coartem here, Colonel Magill predicted, but it had "its arm twisted by the government."

Silvio Gabriel, the company's manager of malaria initiatives, agreed. "But Coartem is, for us, basically for public relations," he said.

However, an unexpected bonus may come the company's way. Under a law that took effect only two months ago, the food and drug agency may issue special "priority review vouchers" to companies that register new drugs against certain tropical diseases, including malaria.

The voucher requires the agency to fast-track the next drug the company brings in for review, doing the job in 6 months rather than the usual 10 to 12 months, said Sandy Walsh, an F.D.A. spokeswoman.

That means little for a low-priced malaria drug, but for a potential blockbuster like Viagra, six extra months of sales before generics can enter the market can translate into hundreds of millions in profits. And Novartis can sell the voucher.

Asked about this, Mr. Gabriel said, "Yes, well, this is a gift from heaven."

But he noted that the company had agreed to start the registration process in 2006, a year before the law that created the vouchers.

http://http://www.nytimes.com/2008/12/23/health/23mala.html?scp=2&sq=malaria&st=cse