Troubled FluMist finds a silver lining

Live vaccine that thudded on debut comes back

A novel influenza vaccine plagued by so much controversy the manufacturer almost gave up making it now is considered a good option for many health care workers during this season’s vaccine shortage, public health officials advise.

The live attenuated influenza vaccine (LAIV) is designed for healthy people ages 5 to 49 — including many health care workers who do not care for severely immune-compromised patients.

"Many health care workers are healthy, younger than 50 years of age and do not work in a bone marrow transplant unit," says William Schaffner, MD, chairman of the department of preventive medicine at Vanderbilt University Medical Center in Nashville, TN. "This raises the possibility [of using LAIV], and I hope hospitals will consider it. This is a season when not a single dose of influenza vaccine should go unused. This is a good match between an available vaccine and a group on the priority list."

Unlike the killed virus in the injected vaccine, LAIV contains weakened flu virus and is administered by nasal spray. The debut of LAIV (FluMist, MedImmune Vaccines Inc., Gaithersburg, MD) during the 2003-2004 flu season was clouded by concerns that vaccinated health care workers could pose a theoretical risk to immunocompromised patients. Because LAIV uses a weakened live virus, recently immunized health care workers possibly could shed and transmit the live viral flu components of the vaccine to immunocompromised patients. Faced with an infection threat to patients and an absence of clear public health guidelines, some hospitals erred on the side of caution and furloughed LAIV-immunized health care workers for up to three weeks. The 21-day period was based on studies of LAIV shedding in immunized children. Subsequent data show health care workers who receive LAIV are unlikely to shed flu virus more than seven days after vaccination, meaning the 21-day furloughs are unnecessary.

The CDC currently recommends that LAIV vaccine should be encouraged for "healthy persons who are ages 5-49 years and are not pregnant, including health care workers [except those who care for severely immunocompromised patients in special care units]." If a health care worker receives LAIV, that worker should refrain from contact with severely immunosuppressed patients (i.e., bone marrow transplant) for seven days after vaccine receipt.

"Most of these [health care workers] are well, and some of them certainly could qualify for FluMist," Julie Gerberding, MD, CDC director, said at a recent congressional hearing.

A cautionary tale

Also testifying at the Oct. 8, 2000 special hearing by the House Government Reform Committee was Jim Young, MD, president of research and development at MedImmune. The company currently has 1 million vaccine doses on the market and is working with the Food and Drug Administration (FDA) to expedite release of another million doses, he said. While that was welcome news, Young primarily described his company’s disastrous venture into flu vaccine production. It was a cautionary tale given the threat of a flu pandemic and the newly underscored vulnerability of the U.S. vaccine supply. For example, the company could scale up production to 20 million doses, but made no such plans after being financially scalded last year.

"The product was approved with a very narrow label indication by the FDA," Young testified. "It has been faced with significant confusion and even misinformation propagated in the marketplace. It has not had strong support by the recommending authorities. It was launched into a climate of overwhelming complacency — a lack of awareness on the part of the public as to the severe illness and death that is associated with influenza."

As a result, the company destroyed 4 million unsold doses last year, he said, adding that 39 of the 152 children who died of flu last season could have received the vaccine under its label approval. "After our initial very disappointing and sobering experience as a flu vaccine manufacturer we spent several months earlier this year evaluating whether we should remain in the influenza vaccine business or whether we should we cut our loses and get out," Young said, lamenting the market and regulatory conditions that whipsawed the company.

"How much bigger does this problem need to become? How many more hearings, analyses, consultants, discussions, and testimonies must there be before any action is taken?" he asked.

Noting that several companies have pulled out of the flu vaccine business, he emphasized that the influenza vaccine business requires enormous investment in clinical development, manufacturing facilities, and meeting regulatory requirements. "Currently, the return on investment is abysmal," Young said.

Demand is strongly influenced by policies set by federal authorities, with flu vaccine recommendations primarily targeting high-risk individuals. However, the burden of flu illness is significant in healthy people who fall outside these targeted age groups and in otherwise healthy unvaccinated school age children who serve as vectors for transmission of influenza to their families and high-risk individuals, he said.

"The vast majority of stakeholders in influenza prevention are reaching the same conclusion. The recommended population for influenza vaccination must be expanded greatly," he said.

A universal recommendation that all Americans received flu vaccine would drive demand for immunization, spur vaccine development, and fuel infrastructure development, he argued.

"This will also ensure the capacity needed to produce even larger quantities of vaccine in the event of an emergence of a new pandemic strain. Ironically, it is the situation like the one we are now faced with — where we are telling healthy individuals not to get vaccinated — which runs counter to the message public health authorities need to send to expand demand," Young said. "Unfortunately, history tells us that it will take several years before many healthy individuals seek vaccination for flu."

(Editor’s note: FluMist will be available this flu season for $16 wholesale per nonreturnable dose or $23.50 wholesale per returnable dose — reflecting a price drop of 50% or more compared to the 2003-2004 season. For more information about FluMist, visit www.FluMist.com.)