The first in a new generation of drugs aimed at taming the flu virus hits the shelves today, just in time for the onset of cool weather, and industry analysts expect patients to besiege doctors for prescriptions despite lingering questions about the drug's effectiveness.
Relenza, a powder inhaled into the lungs--could be a blockbuster in the same class with drugs such as the arthritis medication Celebrex and impotence aid Viagra, if the millions of people struck by fever, coughing and clogged sinuses decide they will do anything to ease their suffering.
Nevertheless, Relenza's effects on influenza are modest at best. The biggest study of the drug, conducted in North America, showed that its use shaves a half-day off a six-day course of the disease--so little that the Food and Drug Administration said the study "failed to demonstrate a convincing treatment effect."
The FDA accepted the results of two smaller studies conducted in Latin America and Europe that, taken together, suggested a reduction in flu symptoms by an average of 36 hours.
To provide that degree of effectiveness, however, the drug has to be given within a day or two after symptoms appear--a tough job for patients, who generally don't know whether they've got a cold or flu and who then have to wrangle a doctor's appointment to get the $37 dose. Only about 5 percent of Americans seek medical care for flu, since rest and drinking fluids can help most people simply ride out the illness.
Those factors help to explain why the FDA advisory panel that considered Relenza earlier this year voted 13 to 4 against approval. The FDA, in an unusual move, approved the drug over the heads of the advisers because "after reviewing the data, FDA found Relenza to be safe and effective for the treatment of influenza A and B," said Laura Bradbard, a spokeswoman for the agency.
The stock of Relenza's maker, Glaxo Wellcome PLC, which closed at $52 yesterday, has traded in a narrow range in the weeks leading up to the introduction of the drug.
Medical experts say that whatever the merits of Relenza, anyone susceptible to flu and its complications should get the time-tested influenza vaccine. People at risk are better off getting vaccinated than acting after the fact, said Norman H. Edelman, the American Lung Association's consultant for scientific affairs.
"It would be unfortunate if the public viewed the availability of this drug as an alternative to vaccination," Edelman said.
Relenza heralds a new generation of antiviral drugs that limit the spread of flu by blocking the action of neuraminidase, an enzyme the virus uses to break off from an infected cell before drifting over to another. A similar drug from Roche Holding Ltd. in conventional pill form, known as Tamiflu, could be approved as early as this month. Both Roche and Glaxo are planning to pitch their wares heavily in the growing direct-to-consumer advertising market.
In its press materials, Glaxo talks about the terrible toll flu takes every year--the 20,000 to 40,000 deaths and 300,000 hospitalizations. But the materials don't note that most of the deaths and serious cases are suffered by those at the highest risk, mainly the elderly and those with compromised immune systems--and that the FDA, in approving the drug, stated: "Evidence for efficacy in a medically higher-risk population was not demonstrated."
Relenza's home-stretch run toward the $92 billion U.S. pharmaceutical market also illustrates how a company's scientific and marketing efforts can go hand in hand, consumer health advocates said. Last weekend, Glaxo announced results of a new study that company officials hope could grow sales even more.
The clinical trial suggested that Relenza might be useful not only as a treatment but also as a preventive. It found that doses for each member of a family could keep the disease from jumping from brother to sister to Mom--80 percent better protection from transmission, in fact, than in families using a dummy drug.
"It's very important," said Michael Elliott, Glaxo's project director for influenza research.
The study, which received much media attention, was funded by Glaxo--a common arrangement in today's pharmaceutical industry that sometimes raises questions of conflict of interest.
The company has not yet sought publication in a peer-reviewed scientific journal for the study or presented its results to the FDA. "That's something we're working to put together," Elliott said.
Independent drug industry analyst Hemant K. Shah estimated that annual sales of Relenza could leap from a few hundred million dollars worldwide to "maybe tens of billions of dollars" if the drug gained acceptance as a preventive measure for flu.
Once a drug is approved for one use, doctors are free to prescribe it for any other use--because the FDA regulates drug companies, not the practice of medicine. These "off-label" uses are crucial in medicine but add risk, since the new use hasn't received FDA vetting.
The diet drugs fenfluramine and phentermine, for example, were both approved by the FDA for use individually, but their wildly popular combined use as "fen-phen" was an off-label practice; researchers later said the combination appears to cause damage to heart valves in some patients.
If companies want to push new uses of their products, they are required to prove to the FDA that a drug is effective in the new role as well. Yet FDA's authority over drug companies' promotion of off-label uses is limited. Federal court decisions recently have denied the agency the power to keep companies from providing doctors with authoritative articles and textbook chapters about such uses, but the FDA still has the authority to restrict the distribution of many kinds of drug promotion.
Thomas Moore, of the George Washington University's Center for Health Policy Research, said the use of studies and a news media hungry for medical success stories is "increasingly becoming a systematic end run" around the agency's drug-promotion rules.
Some FDA critics say that the agency, once vilified by industry, patient groups and Congress for moving too slowly to approve new drugs, has relaxed its standards--and they hold up Relenza as a case in point. Sidney M. Wolfe, executive director of Public Citizen's Health Research Group, has said the drug "barely works" and "would not have been approved 10 years ago."
But the chief counsel for a group that sued the FDA to loosen the rules on off-label promotion was not troubled by Glaxo's release of the flu-prevention data.
"I would say in general the public is well served" by getting information that can improve public health, said Richard Samp of the Washington Legal Foundation, so long as the information is released in an "appropriate forum" and with "appropriate caveats" about the limits of scientific knowledge.
"I don't think Glaxo is doing anything funny," drug industry analyst Shah said.
But he added: "Something like this would not have been allowed 10 years ago. We are in a different political environment, and this is a different FDA."