http://www.washingtonpost.com/wp-dyn/articles/A56230-2003May29.html

Nasal Vaccine Set to Take On Flu Shot

By Michael Barbaro

Washington Post Staff Writer

Friday, May 30, 2003; Page E01

With the flu season just months away, it's nearly decision time for Michael Hoover: Endure the pain of a vaccine shot or try to dodge the virus again this year.

"I probably should get vaccinated, but who wants to get poked?" said the 44-year-old Treasury Department employee, who has forgone the shot for 10 years.

Squeamish consumers such as Hoover may soon find relief in a needle-free flu vaccine that is squirted into the nose, rather than injected into the arm. The Food and Drug Administration is expected to approve the vaccine, called FluMist, by the end of next month, which would put it on pharmacy shelves in time for the 2003-2004 flu season.

FluMist's manufacturer, MedImmune Inc. of Gaithersburg, says the painless alternative to the flu shot could dramatically increase the number of people who seek flu immunization, preventing many of the 114,000 hospitalizations and 36,000 annual deaths from the disease.

Approval could hand MedImmune its second blockbuster drug and cement its place in the highest ranks of the biotechnology industry. The 15-year-old company, by far the Washington region's wealthiest drug developer, expects to cross the $1 billion revenue mark this year, driven largely by sales of Synagis, a drug that prevents a respiratory disease that can kill premature babies.

But questions linger about just how widely its nasal flu vaccine would be used. Unlike the injectable flu vaccine, which contains a dead version of the virus, FluMist contains a live but diluted virus that could pose a health risk to people with weakened immune systems. So FluMist is expected to be approved only for healthy people between the ages of 5 and 49 because federal regulators still have concerns about its safety and effectiveness in the elderly and young children, who are most vulnerable to flu.

That leaves out customers who are most likely to get a flu vaccine: adults over 50 and anyone over 6 months old who has certain chronic conditions or immune system diseases. MedImmune said it will seek clearance to sell FluMist to people in those groups later, a task that industry analysts say will require at least two years of further testing and paperwork.

The U.S. Centers for Disease Control and Prevention estimates that only 13 percent of healthy people under 50, or about 17 million Americans, got flu shots last year. That included a relatively small number of children.

"The question is whether MedImmune will be able to get healthy adults to turn off the football game, get off the couch and get a shot up the nose to prevent a disease that, for most, is not life-threatening," said Joel Sendek, a biotechnology analyst at Lazard Freres & Co.

James G. Hamilton, a family practitioner in Durham, N.C., who has written extensively about fear of needles, says FluMist will sell itself. "People who are frightened of needles will avoid doctors for years, so they will go without immunization for years," he said. "There would be no fear with a nasal spray."

Price remains another potential barrier to widespread FluMist adoption because a typical dose is expected to cost at least $30, more than twice that of a flu shot.

MedImmune officials declined to be interviewed for this story because FluMist is under FDA review. But in recent conference calls with Wall Street analysts, the company has forecast revenue between $120 million and $140 million for FluMist in 2003.

For the first flu season, MedImmune says it can only produce up to 6 million doses because of manufacturing limitations, a number that analysts say the company should have no trouble selling.

The bulk of first-year vaccinations will be given by pediatricians, primary care physicians and pharmacists, the company said. But for now it is unclear whether patients will be able to self-administer the vaccine, which is sprayed into both nostrils with a small syringe.

Medical experts say FluMist offers stronger immunity against the flu than an injectable precisely because of where it is administered. The live flu virus in the vaccine can only grow in cooler temperatures in the nasal passages, where it can prevent infection, but not in the warmer lungs where it might trigger illness.

Tim Uyeki, a epidemiologist and flu expert with the CDC, said the result is the same general immune response caused by an injected vaccine with "the added benefit of an immune response at the points where natural infection occurs."

MedImmune's entry into the flu-vaccine market comes just as its partner, Wyeth Pharmaceuticals, is pulling back from it. Six months ago, Wyeth said it would stop manufacturing its flu shot Flushield and called its sales performance "very disappointing."

Wyeth's move is viewed as a vote of confidence for FluMist, but it also highlights the financial and logistical difficulties that vaccine manufacturers can encounter. They must reformulate their products each flu season to protect against the most threatening strains, mount education campaigns to combat persistent fears that vaccines cause the flu, and try to predict demand for a product whose use varies each year.

Wyeth plans a three-year, $100-million education campaign about the advantages of a nasal flu vaccine and the dangers of the flu. The goal, executives said during a recent presentation to investors, is to turn FluMist "into a household name."

A survey of 800 doctors carried out by brokerage SGCowen Securities last year indicates that the vast majority would use the new vaccine and recommend it to their patients, an important endorsement because much of FluMist's early use will occur in doctors' offices, analysts said.

"The factor Wall Street is trying to gauge is whether premium pricing affects sales of a flu vaccine," said Philip Nadeau, a biotechnology analyst at SG Cowen, which said it may offer investment banking services to MedImmune in the coming months. Nadeau predicts many patients will pay out of pocket to avoid a flu shot.

Analysts suspect some may bristle at FluMist's higher cost, particularly the first year after approval. But Gordon Grundy, senior medical director for Aetna Inc.'s northeast region, said the insurer is likely to shell out more money for what it considers preventive medicine.

FDA approval would mark the end of a long and often bumpy path for FluMist. More than 40 years ago, scientists at the University of Michigan, backed by a military grant, began researching new flu vaccines to prevent a recurrence of the 1958 flu pandemic, which killed nearly 70,000 Americans. By 1967, an epidemiologist at the university, Hunein F. Maassab, achieved the breakthrough: a live virus that conferred immunity without causing infection.

Excited by the innovation, the National Institutes of Health took over the vaccine's development during the next two decades, adding technology and sponsoring large tests to study its safety and effectiveness in humans. In 1995, Aviron of Mountain View, Calif., licensed the vaccine from the University of Michigan with plans to bring it to market. It reformulated the vaccine as a nasal spray and funded the large patient tests needed to prove its safety and effectiveness to government regulators.

Still, FluMist failed to clear crucial regulatory hurdles until MedImmune bought Aviron -- and with it FluMist -- in 2002 for $1.5 billion. Since then, an FDA advisory panel charged with reviewing patient data endorsed the vaccine, which typically paves the way for full agency approval.

© 2003 The Washington Post Company