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Bioterror: Vaccines vs. antidotes

By Scott Gottlieb

If terrorists exposed your hometown to a deadly virus, which would you want: a vaccine that prevents infection or a drug that effectively treats it after a person has become ill?

The vaccine might be the right choice for the rest of the country, but for many people in your city, it would be too late. The virus has already infected them. Their best bet is the drug treatment. But the chances are that no such treatment is readily available for your city's bioterrorism victims.

Last week, federal health officials sent out detailed guidelines to states for quickly vaccinating entire populations against the spread of smallpox as a result of a terrorist act. The Department of Health and Human Services is working to stockpile enough doses of vaccine to protect every American.

This still assumes that the vaccine can be distributed quickly after an attack, before people develop symptoms. It also assumes that there will be enough volunteers (it will require thousands) to administer the vaccines. Further, it assumes that Americans will stand in neat lines to receive the vaccine. More likely, there will be widespread panic. Finally, it assumes that we're willing to accept the deaths of those first to be infected, for whom vaccines would be too little, too late. The smallpox vaccine only offers protection after exposure if it is administered within about four days.

Instead, we should be focusing on antidotes. The technology already exists to come up with treatments for some of the favored agents of biowarfare - medicines that, given after an outbreak, could turn deadly infections into ordinary illnesses. There are some anti-viral drugs that could effectively treat smallpox that are already on the market for other diseases, and even better drugs that could be targeted specifically to the smallpox virus. Yet they languish on laboratory shelves. None of these novel antidotes are likely to make it to the market anytime soon.

So far, Washington remains stuck in first gear, debating whether the development of antidotes is a scientific task best handled through a command and control approach run by the Pentagon, or by dangling incentives before private drug companies. Congressional hand-wringing continues amidst almost weekly disclosures that suggest we're still learning the true scope of the threat.

Progress has been achingly slow, largely because funding is negligible. Private investors don't want to pay for it, arguing there's no sure market. Government grants have been stingy.

Bioterrorism is devoid of all the qualities that make a suitable market - among them, a patient population that can be readily estimated and the freedom to set a price that would yield a reasonable profit. Yet only deliberate efforts to make antidotes are likely to yield the drugs we need.

It's a national challenge that federal health officials need to embrace in earnest. Government grants and laboratories only prime the research pump, producing few tangible cures. The one large project the Pentagon has managed, production of an anthrax vaccine, has been an abject failure. The best new drugs come from entrepreneurial companies looking for profits. The government should stipulate what kinds of drugs it wants, and a minimum bid that it would pay. Some biotech executives say it would take $500 million to lure them into this kind of research. This is similar to the way the government bids on other defense items.

Effective treatments for smallpox may already exist, drugs that could mitigate much of the death and suffering that the virus causes as well as quell much of the fear it incited. But none of the drugs are being aggressively developed as treatments against the virus. The scant research that's going on has been painfully slow. One promising drug, Cidofovir, has been successfully used in animals infected with smallpox, and there's every reason to believe it works in people. It's the best evidence we'll get that a drug works before we're actually attacked, but so far, Cidofovir isn't being stockpiled.

Cidofovir, however, is far from ideal. It needs to be given intravenously and sometimes can cause kidney problems. As with many of the drugs that are believed to work against smallpox, it grew out of research into AIDS. New versions of these drugs, designed specifically to target smallpox, may work better. Cidofovir's maker has at least one such molecule on its lab shelves.But no new versions are being developed, largely because there is no primary market for them against a recognized disease like AIDS, and no reasonable framework for commercializing them solely for use against bioterrorism.

Given that the government won't buy Cidofovir because it is unconvinced that it needs treatments when it has vaccines, there's no certainty that it will buy something better.

Antidotes would also transform the threat posed from anthrax. Antibiotics like Cipro are usually little help after a patient has become seriously sick from anthrax because these drugs don't neutralize the deadly toxin that anthrax releases. This toxin is the bug's real agent of destruction, eventually suffocating its victims by causing fluid to build up in their lungs.

Cipro needs to be given early, before the bacteria have released the bulk of their toxin. Last October, we got lucky. Cipro was handed out early after the anthrax infections began because we had some idea of who had been exposed. Still, 5 of the 11 people with full-blown anthrax died.

An effective antidote would disable the toxin as it coursed through a victim's blood, turning anthrax into a nuisance, but not a killer. Some chemicals failed as experimental cancer drugs but appear to disable the toxin. So do some manufactured antibodies drawn from the same technology that turned medicines like Herceptin and Rituxan into cancer cures. Antibodies are also being targeted against other feared bioweapons such as Ebola and Marburg viruses.

But all of these drugs remain on laboratory shelves, unavailable if Americans are attacked.

The threat from bioweapons will remain with us for many years. Right now, doctors are dependent on vaccines because there's not enough incentive to produce anything better. Yet with enough money and abridged clinical trials, the United States could have an effective antidote in only a few years. Such an arsenal of effective drugs could turn the pathogens of war into ordinary illnesses and, by its very existence, deter those who want to hurt Americans.

Scott Gottlieb, a practicing internist, is a resident fellow at the American Enterprise Institute and the editor of the Gilder Biotech Report