A current, unscheduled review of biodefense funding and procurement processes by federal health officials may lead to more money for two Maryland companies developing new anthrax vaccines.
The "end-to-end" review, due on the desk of Health and Human Services Secretary Kathleen Sebelius next month, was prompted by the slower-than-expected development of an H1N1 vaccine last year, plus new reports giving the nation's biodefense capabilities failing grades.
PharmAthene of Annapolis and Emergent BioSolutions of Rockville have been working on next-generation anthrax vaccines for years. Also, Human Genome Sciences of Rockville sells an anthrax treatment to the federal government and is seeking marketing approval by the Food and Drug Administration.
Officials at those companies, plus leaders in federal laboratories and agencies, say much progress has been made since the anthrax mail attacks of 2001 that killed five people and sickened dozens more.
In response to the attacks, which targeted political leaders and others, Congress boosted biodefense funding for the National Institutes of Health and created a biodefense agency called the Biomedical Advanced Research and Development Authority, which launched Project BioShield to procure new vaccines and other anti-anthrax products. Last month, the FBI wrapped up its probe of those attacks, saying Bruce Ivins of Frederick, a researcher at Fort Detrick, was responsible.
But frustration still permeates a select community of anthrax experts and the companies, due to what some say is inadequate BARDA funding and the very newness of the issue.
‘Harassment' over contract
Competition among the anthrax vaccine companies has heated up.
During a conference call Wednesday, David P. Wright, CEO of PharmAthene, called a competitor's protest of a federal contract with PharmAthene, filed March 19, "harassment."
The rival — Emergent BioSolutions — protested a BARDA modification of its contract with PharmAthene on Feb. 23, providing an additional $78.4 million to support the company's development of its SparVax anthrax vaccine. Wright said SparVax is ready for production under a special approval process created for biodefense products called "the animal rule," in which a product that can be shown safe and effective in two kinds of laboratory animals can win approval.
An Emergent spokeswoman declined to comment on the protest.
The protest activated a BARDA rule that suspended work on the modified contract until at least June 11. Meanwhile, PharmAthene will continue developing the vaccine with prior BARDA funding, Wright said.
The company this week reported a net loss of $32.3 million last year, compared with a net loss of $36.4 million in 2008. Revenues fell to $27.5 million from $32.9 million.
BARDA works with many companies to advance vaccines, antibodies, antitoxins, antibiotics and other products against potential and actual biowarfare agents.
Wright expressed concern in a previous interview that the pace of federal funding has been inadequate to fully protect the public from an anthrax attack and that until recently there have been mixed signals from the administration on biodefense.
Wright said another anthrax attack could be "much worse" in human and economic damage than the Sept. 11 attacks and that damage would persist much longer. People would die and the U.S. economy could be crippled by a single-city anthrax attack, he said.
One reason: Anthrax can remain viable on surfaces for up to 30 years, he said.
"Imagine not being able to come to Washington, D.C., if you have not been vaccinated for anthrax," Wright said.
‘Do we have enough? No'
While PharmAthene has yet to sell an anthrax vaccine, one of its main competitors for the new federal contract, Emergent BioSolutions, has been selling the only FDA-approved vaccine to the federal government for years. But it's a relatively old version, requiring more injections over a longer time than what the government is seeking in a new vaccine.
"I don't know of all the government plans, but in terms of medical products, there are now a number of products available to the government to protect the nation," said Daniel J. Abdun-Nabi, Emergent's COO.
The government may have a "baseline level of protection," he said. But "do we have enough? No."
Abdun-Nabi called the BARDA effort "an admirable job of bringing products along to the point where they can be put into the stockpile and they can be made available to protect the public in the event of an attack. I think they recognize and have stated publicly it's not where they want to be."
In December, BARDA canceled its request for proposals for a new genetically engineered vaccine — called a recombinant protective antigen, or rPA, vaccine — saying the vaccine companies could not deliver a product within eight years.
Rather than issue a new request, the agency said it would ask vaccine developers to submit "product development plans under special instructions to an existing broad agency announcement ... that supports the development of medical countermeasures for chemical, biological, radiological and nuclear threats."
Emergent's products include its anthrax vaccine, BioThrax. Still, the company acknowledged in a regulatory filing, "We face significant potential competition for the supply of anthrax vaccines to the U.S. government."
Emergent is developing an improved version of BioThrax, which was created in the 1970s, that would require fewer injections. Besides working on the new rPA vaccine, it's also developing an anthrax immune globulin, which would be administered to infected patients in an emergency room.
Emergent also wants to ramp up its BioThrax production to as many as 30 million doses a year. It has an $80 million manufacturing plant in Michigan and has opened a laboratory in Gaithersburg. The company has secured $1.2 billion in federal contracts during the past five years, Abdun-Nabi said.
"BARDA has done an amazing job with the limited dollars they have available in generating multiple products," he said. "The next step is for additional funding after the original $5.6 billion was allocated for 2008 to 2013. It needs to start thinking of the next steps, to enable finishing the products."
BARDA is ‘hamstrung'
The industry is stuck in "the valley of death ... because no one is going to take it from early development to approval because there is no customer other than the government, and that is not guaranteed," Wright said.
"The government did not fund BARDA well enough to do the job from the very beginning," he said. "But here you have a group of people of at BARDA who are very capable and are working unbelievably hard. But they are hamstrung."
A recent "report card" issued by the bipartisan Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism, or the Graham Report, gave the nation an "F" in preparedness for a biological attack. Another report from Purdue University drew similar conclusions.
Wright calls PharmAthene's SparVax "very much a modern vaccine using modern technology," compared with BioThrax. SparVax requires only three injections over 60 days, while BioThrax requires five injections over 18 months.
PharmAthene also is working on a monoclonal antibody that would provide instant immunity for first-responders.
The funding problem has been one of perception, Wright said.
"Unfortunately, biodefense is looked at as a health issue," he said. "The problem is that it is really a defense issue. If you wanted to spend $3 billion on a B1 bomber or two, the country doesn't think anything about it because that's defense and we need national security."
"I take the point," said Nichole Lurie, assistant secretary for preparedness and response with Health and Human Services and overseer of BARDA.
"But we have been through a number of health issues and there is no doubt that people take this seriously," Lurie said. "We are not all the way there. We are a whole lot better off than we were 10 years ago."
But she is concerned that BARDA is working primarily with small companies that "right now don't have the capability to scale up and manufacture on a large enough scale."
Will the new review lead to more funding?
"If you are going to be serious about advanced development, you've got to fund it," Lurie replied.
As for a major anthrax attack on an office building in Washington, "we would be in very good shape," she said.
"In the strategic national stockpile, we have antibiotics in it, we have some anthrax immunoglobulin in it, some vaccine in it," Lurie said. "Is there enough? We are working toward a bigger stockpile of vaccine."
Overall, said Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health's National Institute of Allergy and Infectious Diseases in Bethesda, "The system is working right now. ... Enemy combatants might see that there is a vaccine and this would be a deterrent.
"I think having said that, you need to realize this whole structure is still a work in progress."
Human Genome Sciences builds on early move
One of the federal biodefense agency's most effective working relationships has been with Human Genome Sciences of Rockville, said Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health's National Institute of Allergy and Infectious Diseases in Bethesda.
HGS was an early player in the anthrax field, winning a federal contract in 2006 to develop raxibacumab, called ABthrax, to treat patients who have inhaled anthrax.
"[HGS] can claim they fostered that approach, yes, a new treatment," Nabel said. "How effective and often it will be used — there are questions still up in the air.
"They have done a good job," he said. "This idea was chosen by the company which said, ‘We think we can do this.' I think it was really driven by their entrepreneurship."
HGS, which reported $1.2 billion in cash and investments at the end of 2009, is well into fulfilling its second order from the Biomedical Advanced Research and Development Authority. HGS posted $162.5 million in product sales and manufacturing and development services revenue by delivering 20,000 doses of raxibacumab to the Strategic National Stockpile in the first half of 2009. In July 2009, the government decided to purchase 45,000 more doses over three years. HGS expects to receive about $142 million from that second order.
But the company's application for marketing approval hit a snag in October 2009, when a Food and Drug Administration advisory panel said it needed more data on HGS's anthrax treatment candidate before it could recommend approving it.
ABthrax differs from other treatments in that it targets the toxins produced by the anthrax bacterium in the body, rather than the bacterium itself. But studies in monkeys and rabbits show that adding it to the conventional regimen of antimicrobials had little benefit.
Currently, the antibiotics known as Cipro and Levaquin are most often prescribed for inhalation anthrax.
The FDA has also raised questions about the reliability and quality of human pharmacokinetic data in the HGS application. Those data include how the body absorbs and metabolizes ABthrax.
Under the Project BioShield Act of 2004, the federal government may purchase products such as ABthrax that have not received FDA approval. If the FDA approves the treatment, HGS stands to collect an extra $20 million under its contract with BARDA.
The company is working with the FDA to resolve the test questions.
"We do understand that this is one of the first applications of the ‘animal rule,' " said HGS spokesman Jerry Parrott. Under this rule, a product that can be shown safe and effective in two kinds of laboratory animals can win approval.
"It is good for the company to go through this process," Parrott said.