FluMist Excels In Key Trial, Maker Says

By Michael Rosenwald and Justin Gillis
Washington Post Staff Writers
Monday, December 12, 2005; 11:36 PM

MedImmune Inc. said yesterday that a new version of its nasal-spray influenza vaccine had proved superior for young children to the standard flu shot in a large global test, a finding that could revive the fortunes of a flagging product and potentially give the world an important tool against pandemic flu.

In a test of 8,492 children in 16 countries, the Gaithersburg biotechnology company compared standard injected vaccine with a new version of its FluMist product, which is delivered as two puffs of mist in the nose. Only 3.9 percent of children receiving FluMist got the flu, versus 8.6 percent of those who received standard flu shots, a 55 percent drop.

This is the third, and by far the largest, study to show superiority for FluMist, which has sold poorly despite periodic shortages of flu shots. The new product still awaits approval from federal regulators, who had previously balked at allowing its use in children.

The $90 million study was MedImmune's last-ditch effort to revive FluMist by proving the product was better at preventing the flu in children under 5 -- a crucial age group for whom regulators did not originally recommend the vaccine when they approved it in 2003.

MedImmune, the region's most successful biotech firm and employer of nearly 2,000 people, appeared to have achieved its goal, even demonstrating that FluMist can protect against circulating flu strains not contained in the vaccine. Company executives had said that poor test results probably would have caused them to dump FluMist.

"The injectable vaccine has been used for more than 40 years," MedImmune chief executive David Mott said in an interview. "We have just demonstrated that with [FluMist] we have the potential to demonstrate 55 percent better efficacy at preventing influenza. That's a pretty important finding."

But several hurdles remain for FluMist, most notably whether the Food and Drug Administration will even approve the product for children under 5 and, if so, whether the agency will let the company claim superiority over flu shots. The study confirmed previous findings that FluMist poses a slight risk of precipitating wheezing episodes among some children.

If the company can make the case that FluMist is better than the flu shot -- and that the wheezing risk is outweighed by better protection against a serious virus -- the company could well have an important product on its hands, although some analysts question whether MedImmune will ever make the $800 million a year on the product that it once promised investors. MedImmune and a pharmaceutical partner, Wyeth, launched FluMist in 2003 with a $25 million advertising campaign. They offered it at more than $40 a dose, at least three times the price of standard vaccine, declaring that people would pay a premium to squirt mist up their noses instead of getting a shot in the arm.

But doctors balked at the price and at a burdensome requirement that the vaccine be stored frozen. Most doctors' offices are equipped only to refrigerate vaccines, not freeze them. The new FluMist can be refrigerated. Most important, the FDA refused to approve the original FluMist in young children and the elderly, the groups that need flu vaccine most. FluMist uses a live, weakened version of the virus, which appears to make it more effective at inducing immunity. But it is also theoretically riskier in vulnerable groups than the injected vaccine, which contains only dead flu viruses.

The 2003 FluMist launch was considered a dramatic setback, and Wyeth eventually walked away from the product. But despite calling the launch "a debacle of the first order," Mott stuck with FluMist through withering investor criticism.

While saying he hoped the new version would win approval in time for the 2007-08 flu season, Mott acknowledged that there are still issues to work through.

In addition to questions about assertions the company can make in marketing materials, Mott said it is unlikely that the FDA will allow the company to claim superiority for the product in official instructions for doctors, though MedImmune will probably be able to include summary results of the recent study.

Also crucial for MedImmune is whether medical groups and public health officials revise guidelines on how to use the product. MedImmune appeared to win support yesterday from a member of the committee that makes vaccine recommendations for the American Academy of Pediatrics.

"This is a better vaccine," said John Bradley, a pediatrician at Children's Hospital in San Diego and a member of the academy's committee on infectious diseases. "It's not as though the old one is worthless. It's just that this one is better enough that I think in the future we're going to move toward giving children the best protection possible."

MedImmune will have to overcome concerns about wheezing, which was seen in 3.2 percent of children using its product versus 2 percent of children who received a conventional shot. It remains to be seen whether other doctors will agree with Bradley that the "risk of wheezing is offset by the benefit of improved protection."

While FluMist is intended mainly for use against seasonal flu, a version could be developed rapidly for a more dangerous strain. Because it is a live vaccine that induces immunity by reproducing in the body, it would most likely be effective with one low dose, whereas studies suggest an injected vaccine would require two large doses a month apart.

In principle, the nasal vaccine could offer crucial advantages in a pandemic, allowing authorities to make many more doses and protect many more people in a given period.

"Historically, a live vaccine induces more potent, lasting and broader immune responses than a killed vaccine," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. "The body is seeing the microbe in a way that is much more analogous to a real infection."

MedImmune shares closed at $35.71 yesterday, up 4.5 percent.

© 2005 The Washington Post Company