Last Updated

03 Dec 2002

Source: Wall Street Journal, March 19, 2002.

AFTERMATH OF TERROR

Drug Isn't Being Stockpiled by U.S. Despite Potential to Fight Smallpox

By MARILYN CHASE, Staff Reporter of THE WALL STREET JOURNAL

An antiviral drug now sold as an AIDS treatment is viewed by many researchers as the most promising experimental agent so far against smallpox in the event of a bioterror attack.

But unlike Cipro, the antibiotic drug against anthrax , the U.S. government isn't stockpiling the antiviral drug, Vistide. That is because of a debate raging behind the scenes among smallpox experts on the best way to handle an outbreak of the disease.

The chief skeptic of the antiviral drug is D.A. Henderson, the government's top bioterror scientist. Dr. Henderson champions the tried-and-true method of containing a smallpox outbreak with strategically applied vaccines, which was instrumental in eliminating naturally occurring cases of smallpox from the world more than two decades ago. In that approach, everyone around the infected patients -- family members, neighbors, hospital staff -- is quickly vaccinated, creating a firewall to stop the disease's spread.

The vaccine doesn't help people who already are infected, leaving them to die or survive with disfiguring scars. Smallpox has a 30% mortality rate, which leads many researchers to believe that Vistide -- while experimental -- should be used to complement the vaccine protocol. Indeed, based on its demonstrated power to suppress the pox in test-tube and animal studies, the U.S. Army Medical Research Institute of Infectious Diseases at Detrick, Md., lists Vistide in its bioterror treatment manual as a possible smallpox treatment. The Food and Drug Administration also sanctions its experimental use should the disease ever re-emerge.

Vistide, generically known as cidofovir, "continues to look good," confirms James LeDuc of the U.S. Centers for Disease Control and Prevention, one of several government agencies that backs the idea of stockpiling it.

Its maker, a small company called Gilead Sciences Inc. of Foster City, Calif., makes the drug to prevent blindness in AIDS patients and isn't out promoting the smallpox angle. But Gilead Vice President John Milligan says, "It would be prudent" to include it in any bioterror first-aid kit.

At 73 years old, Dr. Henderson is a revered figure for his role in the World Health Organization's epochal work in eradicating smallpox from the world by 1980. Using vaccine, he is credited with saving tens of millions of lives. However, his critics say his focus on vaccines slights the important job of developing antiviral drugs.

Granted, Vistide, in addition to being experimental, has drawbacks. It requires intravenous delivery and can cause kidney damage if used over a long period. But in animal tests, a single dose of Vistide protected macaque monkeys from lethal exposure to monkeypox, a close relative of smallpox.

Vistide is just the first in a host of experimental compounds against smallpox now being developed at universities and companies. However, Vistide is the furthest along because it is the best-studied and already marketed for AIDS. Right now, if there were a smallpox bioterror attack, Vistide is the only drug in hand that shows any promise for treating the disease.

Given that, some scientists question why the U.S. government is devoting massive resources to stockpiling 280 million smallpox vaccine doses but won't stockpile Vistide. Should people rush to get the drug on their own, Vistide supplies are likely to run out quickly.

Dr. Henderson remains sharply skeptical about the potential for antiviral drugs to change the course of the lethal and disfiguring disease.

"[Vistide] is an experimental drug," says Dr. Henderson. "After an individual comes down with fever and rash, would we be able to treat them? We'd be better off looking at treating [vaccine] complications," he says. "That's the most prudent way to go about this."

As director of the Office of Public Health Preparedness -- a position created to craft an urgent response to the events of Sept. 11 -- Dr. Henderson wields considerable clout in shaping the nation's medical preparedness, frustrating scientists who see potential in antivirals.

"D.A. did an important thing" in his global eradication campaign, says smallpox antiviral researcher John Huggins of the Army Medical Research Institute in Maryland, known as USAMRIID. "But he doesn't understand antivirals," he laments. "I wish he'd give us a fair shake."

In addition, Dr. Henderson is opposed to spending core resources for pox treatments he considers uncertain. Cidofovir isn't cheap, currently costing $705 wholesale for a one-dose vial to treat AIDS patients with cytomegalovirus who take it indefinitely to prevent blindness.

Dr. Henderson stresses that vanquishing viruses is vastly tougher than making antibiotics against bacteria. Viruses are parasites taking refuge in human cells, so any drug that kills the virus also hurts human cells. Recently, however, Peter Jahrling, a scientist at USAMRIID, used massive doses of variola, the smallpox virus, to reproduce a super-lethal disease in monkeys. Indeed, it was more lethal than the human disease -- killing 85% of monkeys compared with 30% mortality in humans. Dr. Jahrling concedes his model has "rough edges," but with some improvement vows he can "get some traction" as a test system for new drugs.

Dr. Henderson begs to differ. "It is quite a long way from being a model," he insists, adding its ultimate value is "not a certainty or even high probability."