US boosts medical stockpile for flu pandemic

Robert Roos

Sep 15, 2005 (CIDRAP News) The federal government is spending about $103 million to boost its small supplies of avian influenza vaccine and antiviral drugs to battle a possible flu pandemic, health officials announced today.

The Department of Health and Human Services has awarded a $100 million contract to Sanofi Pasteur for an unspecified number of doses of vaccine for the H5N1 strain of avian influenza. The virus has killed more than 60 people in Asia and is considered likely to trigger a flu pandemic. Sanofi made 2 million doses of the vaccine under a previous contract with HHS.

In addition, HHS said it has paid $2.8 million for enough doses of GlaxoSmithKline's antiviral drug zanamivir (Relenza) to treat 84,300 people. The purchase adds to an existing stockpile of about 4.3 million treatment courses of Roche's oseltamivir (Tamiflu), HHS spokesman Bill Hall told CIDRAP News.

"These purchases build on the department's plans to buy enough vaccine for 20 million people and enough antivirals for another 20 million people," the HHS announcement said. The doses will be stored in the Strategic National Stockpile for use in the event of a pandemic.

"These countermeasures provide us with tools that we have never had prior to previous influenza pandemics," HHS Secretary Mike Leavitt commented in the HHS release.

HHS said it has already received the zanamivir. The vaccine contract calls for Sanofi to make the vaccine at its plant in Pennsylvania between now and late October, the company said in a news release.

How many people the vaccine would cover is still to be determined by ongoing clinical trials, HHS said. In the first clinical trial of the vaccine, researchers found that it took two 90-microgram doses to stimulate what was regarded as an adequate immune response. That's about 12 times the 15-microgram dose contained in a typical seasonal flu shot.

"However, further clinical testing is underway, including the evaluation of techniques that may reduce the amount of antigen (active ingredient) per dose needed to achieve effective individual protection," the HHS statement said.

Hall declined to say how many people the vaccine contract would cover on the basis of two 90-microgram doses per person. "We know that microgram number is going to decrease," possibly by adding an adjuvant to the vaccine, he said. "Until we've gotten a lot of the research done and have a better understanding of what the optimal formulation and dosage will be, it's not in anyone's interest to speculate on a number."

Today's announcement follows two previous HHS contract awards to Sanofi Pasteur (formerly Aventis Pasteur) for the H5N1 vaccine. The company won a contract in May 2004 to make about 8,000 doses for clinical trials; in September 2004 it signed a $13 million contract to make 2 million doses for use by health and emergency workers and to prepare for possible mass production.

Zanamivir and oseltamivir make up the class of antivirals called neuraminidase inhibitors, which block an enzyme that allows flu viruses to leave a host cell. When used within the first two days of flu symptoms, they make the illness less severe and shorten its course by about a day.

Zanamivir comes in a powder that is inhaled, while oseltamivir is sold in capsules. In the United States, zanamivir is licensed for treatment of flu in people aged 7 years and older; oseltamivir can be used to treat patients from the age of 1 year and can also be used to prevent flu in patients older than 12 years. Zanamivir is not approved for preventive use.

Disease experts have repeatedly warned that the world's supplies of antivirals and capacity for producing vaccine are far from adequate for coping with a flu pandemic. For example, in June, the Infectious Diseases Society of America said the United States should have an antiviral stockpile large enough to treat 52 million to 84 million people and to use preventively in 15 million to 40 million more.

Hall said the current goal of having enough antiviral medicatioin to treat 20 million people and enough vaccine doses to cover another 20 million was announced by Leavitt in July and was based on current manufacturing capacity and other factors.

He said no decision has been made on whether vaccine or antivirals from the US stockpile could be used to help snuff out an emerging pandemic overseas, should the need arise. "I think those issues are being discussed at very high levels," he said.

Infectious disease expert Michael T. Osterholm, PhD, MPH, called the HHS purchases "a critical first step."

"This sets the platform for much additional work that will need to be completed if we are to aggressively respond to the future pandemic of influenza," said Osterholm, director of CIDRAP, publisher of this Web site. "What we need to do now is fill the gap between this limited amount of vaccine and trying to stop a pandemic that would require vaccinating 6.5 billion people."

He said the H5N1 strain used in the vaccine, which dates from last year, "will not be the strain that ultimately circulates" in a pandemic. But the vaccine "could serve as an important priming dose in a two-dose series," in which the second dose would (it is hoped) be more closely matched to the pandemic virus, he said.

Similarly, Osterholm called the zanamivir purchase a good first step. He said there is no guarantee that the neuraminidase inhibitors will be effective in battling a pandemic flu virus if the virus triggers a "cytokine storm," or immune system overreaction.

However, he said, "The only thing we can do right now is attempt to stockpile as much antiviral medication as we can. . . . If neuraminidase inhibitors are clinically effective, we'll ultimately need a quantum leap in production and stockpiling, as opposed to incremental increases."