|Doubts Are Raised on Push for
By ERIC LIPTON
Published: December 11, 2004
http://www.nytimes.com/2004/12/11/national/11anthrax.html (must register to view original article)
In ordering a new $877 million anthrax vaccine last month, the federal government said it was a major step toward creating a "bioshield" to protect Americans from germ warfare. But delivering that protection may be difficult: the vaccine is unproven in humans, the maker has legal and accounting troubles, and health officials are not prepared to distribute the vaccine quickly if it is needed.
Bush administration officials, as well as the top executives at VaxGen, the manufacturer in California, say they are confident they can fulfill their promise.
"This program needs to be a success for all of us - the federal government, for the company and for the American public," said Lance K. Gordon, VaxGen's chief executive.
But some scientists say the effectiveness of the vaccine, which is to be delivered starting early in 2006, is still in doubt.
"When the day comes and we have to give this to 20 million people, in terms of this new vaccine, what will happen?" said Jack Melling, former head of Britain's biodefense vaccine program and now a consultant to the United States Government Accountability Office. "The jury is still out; it is still an open question."
The vaccine contract, enough to inoculate 25 million Americans, is part of a $5.6 billion effort called Project BioShield intended to build a drug stockpile and other defenses against any diseases terrorists might try to inflict on the population.
VaxGen, which is to produce 75 million syringes of vaccine with a formula it is still fine-tuning, has had recent setbacks, including the removal this summer of its stock from the Nasdaq market because of accounting problems and lawsuits from investors who say it exaggerated the prospects for its AIDS vaccine, which has been abandoned.
The federal government has had its own recent embarrassments with vaccines: the shortage of flu vaccine this year and the aborted effort in 2003 to vaccinate health care workers against smallpox.
Some experts question the value of the whole Project BioShield, as the investment in the bioterrorism stockpile will perhaps mean less money for research or treatment of other health problems, like AIDS, cancer or even the flu.
"This anthrax threat is extraordinarily exaggerated," said Victor Sidel, a professor at the Albert Einstein College of Medicine in the Bronx and past president of the New York City Public Health Association. "All of this is simply playing to the politics of fear."
Bacillus anthracis, the naturally occurring, spore-forming bacterium that causes anthrax, most commonly affects livestock. Before the mailing in 2001 of anthrax-laced letters that killed five people and sickened 17 others, the disease had been extremely rare among humans in this country, particularly in its most dangerous form, when it is inhaled into the lungs.
Federal officials consider anthrax one of the most serious biological threats. The culprit in the 2001 mailings is still at large. And a study published last year by the National Academy of Sciences suggested that the aerial release of 2.2 pounds of anthrax in a major American city could cause more than 100,000 deaths.
"Our most important priority is to safeguard the American people," Tommy G. Thompson, the secretary of health and human services, said last month in announcing the VaxGen contract. "This vaccine is a key step towards protecting the American public in the event of another anthrax attack."
Pasteur developed the first anthrax vaccine in the 1880's, but it was only for use in animals. Human anthrax vaccines date from the 1950's and 1960's, when the United States and other governments started to experiment with anthrax as a weapon.
The only anthrax vaccine now approved for use in this country requires six injections over 18 months, an extremely long time for a vaccine. It is hard to produce in large batches: it would take a decade to make 75 million doses under the current production method, federal officials said Because of the imprecise way it is made, there are great variations in potency, which researchers believe has contributed to side effects in some military personnel.
The Department of Health and Human Services also has a stockpile of more than one billion antibiotic pills, enough to treat 20 million people for the required 60 days. But because inhaled spores can live longer than two months and antibiotic resistant strains of anthrax might emerge, an effective vaccine is considered an important protection, federal health officials said.
The vaccine that VaxGen is now testing was developed by researchers at the United States Army Medical Research Institute of Infectious Diseases, who made a purified, genetically engineered vaccine that could be given with fewer shots and have fewer side effects.
To accelerate Project BioShield, the Bush administration, with the blessing of Congress, intends to buy vaccines even before they have been approved by the food and drug agency as safe and effective. VaxGen does not intend even to submit a license application to the agency until 2007, the year it must deliver the final shipments of the $877 million order. That may mean that approval for the vaccine might not come until after the 75 million doses must be thrown out, as they can only be stored in syringes for about two years.
The Army Medical Research Institute, at Fort Detrick, Md., already has done tests on mice, guinea pigs and monkeys, producing sometimes conflicting results. Monkeys, which are closest to humans, were well protected, but guinea pigs and mice often died. That has led some doctors, like Steven M. Wolinsky, head of the division of infectious diseases at Northwestern University's medical school, to question if VaxGen's anthrax vaccine, as formulated, will be effective.
"We don't know the concentration of antibodies in humans that are needed to confer immunity to anthrax," Dr. Wolinsky said.
Anthrax is so dangerous that the live bacteria cannot be used when testing the vaccine on humans. VaxGen tests on volunteers - about 600 have been given the experimental vaccine - simply measure immune system response and side effects of the vaccine, without actually exposing anyone to the disease.
Federal officials said they remained confident that the VaxGen approach would provide the necessary protection. "There is no guarantee of anything unless you do it," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. "But there are certainly suggestions that the science here will work."
And while there may be better alternatives someday -researchers at Harvard Medical School and the Pasteur Institute in France are studying different approaches that may provide more robust protection than the VaxGen vaccine - it is critical to push forward, federal officials said.
"For us to say let's wait and do nothing," said Dr. William Raub, principal deputy assistant secretary for public health emergency preparedness at Health and Human Services, "would be an abdication of our responsibility for homeland security."
If an attack occurs, the plan would be to treat the public with a combination of antibiotics, followed by vaccination. Health officials hope to shorten antibiotic treatment from 60 days, as long-term use of antibiotics is itself potentially hazardous. It would be critical to rapidly distribute antibiotics and vaccines, a task Bush administration officials acknowledge they could not adequately do today.
"We are not where we want to be by any means," Dr. Raub said.
For VaxGen, the first challenge is to resolve its financial affairs. The company was the only bidder to make it through the formal competition for the contract; few pharmaceutical manufacturers have ventured into the risky world of vaccine production for bioterror threats. VaxGen, in Brisbane, Calif., is also a tiny company, by industry standards, with 220 employees, and has yet to earn a profit since its founding in 1995. The anthrax contracts - the company had previously landed $101 million to finance research on the vaccine - total just over $1 billion, representing almost all of its current or committed future revenues.
The company's stock was removed from the Nasdaq listings in August after the company and its auditors concluded that it had not been properly recording revenue received from its existing anthrax contracts with the government, resulting in an underreporting of its revenues and an overstatement of its losses. There was no accusation of improprieties related to the accounting trouble, but still it was an embarrassment for the company. Also in August, a former VaxGen manager responsible for preparing its federal Securities and Exchange Commission reports was fined for insider trading.
VaxGen, meanwhile, is defending itself against lawsuits by investors who claim the company misled them about its progress on its AIDS vaccine. Tests showed it was not effective, and VaxGen has abandoned its work on the vaccine..
For now, VaxGen's stock is still listed for trading on what is known as "pink sheets." The company's stock, which traded as low as $3 after a February 2003 announcement initially indicating the failure of the AIDS vaccine, surged after the $877 million anthrax contract, settling at $17.45 yesterday. After it re-audits its finances and submits required federal financial reports, it will apply for reinstatement to Nasdaq market.
Officials at Health and Human Services said they were well aware of all these issues. Dr. Gordon, who took over VaxGen in September 2001, has spent two decades in the vaccine business, including seven years at Connaught, where he invented and oversaw the development of a vaccine that prevents infant meningitis, a record that has contributed to confidence in the industry that VaxGen can handle this new assignment. Dr. Raub and others said the federal government will be monitoring the company's progress very closely.