OK found a link to today's WSJ re:Glaxo
The article is on an influenza drug and is irrelevant to Zicam except that the molecular modeling techniques (used to figure out the ICAM structure in rhinovirus infections) were used to figure out how to make this drug. This lends some credence to Hensley's documented and referenced claims (for the skeptical out there). The article also describes the cost of these drugs and how the medical system will fight prescribing them. This lends credence to my previous post. I personally believe that if Zicam is accepted by the medical community, patients will be encouraged to treat the common cold at home with a cheaper OTC remedy rather than see their doc unless they are very sick. There is certainly a place for drugs like Rilenza, but it won't be for treating common colds, for which it it NOT work.
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Excerpts:
The other is Rilenza, from British-based Glaxo. They work in a similarly innovative way to stop the virus from replicating furiously and spreading swiftly inside a person's respiratory tract.
But they aren't miracle cures. Neither will stop a case of the flu dead in its tracks. Instead, studies show that if they are taken within the first two days of an attack, they can reduce the amount of virus inside a person, thereby shaving a day or so off the flu's typical run, and can also diminish the severity of the symptoms felt.
This effect "may not seem like a lot, but in the clinical trials, people tell us that getting back on their feet faster and being able to function sooner is a valuable and important benefit," says John Treanor, a researcher at the University of Rochester (N.Y.) School of Medicine.
Role in Prevention?
Drs. Hayden and Treanor and others who have tested the drugs in nursing homes and hospitals say the drugs may serve a public-health benefit by preventing an episode of flu from occurring in the first place. In tests last winter -- some results of which will be reported at a science meeting in San Francisco next week -- healthy people who used the drugs after being exposed to the flu seemed to be shielded from the virus. This may prove especially beneficial in protecting frail, elderly people in whom the flu can foster bronchitis, pneumonia or other dangerous infections. Such complications cause 20,000 to 40,000 flu-related deaths in the U.S. each year.
In a report to be presented at the San Francisco meeting, health workers at Toronto's Riverdale Hospital, a long-term-care facility, say they foiled a flu outbreak on one ward last winter by giving Rilenza for several weeks to elderly patients who weren't yet infected but were probably exposed.
In addition, Glaxo and Roche are both doing studies of whether their drugs can be used by day-care centers and within families to block the flu from spreading. "Even though the drug won't be approved for this use right away, I do believe the ultimate best use of these drugs will be in" prevention, says Stefan Gravenstein, director of Glennan Center for Geriatrics and Gerontology, a long-term-care facility associated with Eastern Virginia Medical School in Norfolk, where he has tested Rilenza.
Still, marketers face a daunting set of challenges. The first, as with any new drug, is getting known. Right now, few potential users of the drugs, or even their doctors, are aware the medicines exist. Rilenza won Food and Drug Administration this summer and got approval for European sales earlier in the year. Roche's Tamiflu is expected to get U.S. approval late next month; in Europe, it is likely to be sold only in Switzerland this winter.
But marketers this time face a special challenge: getting people to rush to the doctor's office at the very first sign of flu. At least initially, the drugs' approval will be only for flu treatment, not prevention. And studies of both drugs show that to be effective, they have to be taken within the first 24 to 48 hours of symptoms. There is some evidence that after just one day of symptoms, the virus has reproduced so much that blocking further replication does little good.
Some public-health officials fret that the new drugs will greatly expand health bills of private and government insurance programs already burdened by a wide array of new and expensive medicines. Both companies' drugs are expected to cost about $45 to $50 for a course of treatment. Some insurers worry that doctors won't be able to distinguish flu from the common cold, and that many patients with non-flu respiratory illnesses will demand the drugs after hearing about them in the ads. There is no diagnostic test to identify the flu virus in patients, and the many viruses that cause the cold won't respond to the new drugs.
The Coming Competition
Meanwhile, interviews with Glaxo and Roche marketers suggest that the challenge of pitching a brand-new type of medicine -- and doing so better than the other guy -- is causing a buzz inside the companies as infectious as the flu itself. "There's real excitement here that we have a novel solution to something that has plagued mankind since antiquity," says Dennis Burns, vice president of new-product planning at Hoffmann-La Roche, the Swiss company's U.S. unit in Nutley, N.J.
The products' differences are likely to heighten the competition. Roche's Tamiflu will come as a once-daily tablet; Glaxo's Rilenza must be taken via an oral inhaler, similar to devices for asthma. "Roche and Glaxo are going to have a great intellectual battle," says James Daly, senior vice president of marketing at Glaxo's U.S. headquarters in Research Triangle Park, N.C. But Myron Holubiak, president of Roche's U.S. drug business, says each company will benefit from the other's marketing because "we will be essentially carrying the same message: that a new therapy now exists."
Whatever their fate in the market, the drugs are already being hailed as a medical milestone. Their origin goes back more than 15 years and involves some clever discoveries by public-health researchers in Australia, as well as a frenzied bit of catch-up by Gilead, the tiny biotech company, and its partner, Roche.
In the early 1980s, virologist Peter Colman and his colleagues at the Australian government's Commonwealth Scientific and Industrial Research Organization in Melbourne weren't hunting for a drug, but were trying to understand why flu varies so much from year to year. It is flu's annual habit of altering its outer mask of proteins that makes the virus so hard to detect, prevent and treat.
Two Main Strains
The virus comes in two major strains, type A and type B, each of which has its own diverse substrains. Each season's new flu variant begins its year-long journey around the globe early in the North American spring when it emerges from domestic and wild fowl in China and other parts of Asia. While the birds are impervious to the virus, they serve as a fertile ground in which new strains arise and then spread to people who haven't been exposed to the bug's new chemical makeup.
Each spring, the U.S. Centers for Disease Control and Prevention and other public-health groups send experts to Asia to identify the new virus. After analyzing the genetic structure of its new disguise, the CDC quickly alerts vaccine makers in the U.S. and elsewhere, who rush to produce vaccines that match the flu variant expected to drift eastward and reach U.S. shores in late November.
"Like others, we were trying to understand what about the protein changes each year that makes the flu so infectious," says Dr. Colman, now director of the Biomolecular Research Institute in Melbourne. They focused on one protein, an enzyme called neuraminidase, that several years before had been isolated by other scientists. After several years of effort, using special X-ray techniques that dissect the atom-by-atom properties of a crystallized version of the protein, the researchers generated a computerized three-dimensional image of the protein. In essence, this snapshot helped Dr. Colman's laboratory "solve" the enzyme's structure and its previously mysterious role in helping the virus reproduce inside infected cells.
To the scientists' surprise, they found that while neuraminidase's outer regions can fluctuate from strain to strain, the virus's internal machinery never changes. This inner structure, which appears in 3-D images much like a deep valley within an undulating mountain range, plays a crucial final role in allowing a newly formed viral particle to emerge from an infected cell and spread to other nearby cells.
This reproductive process is repeated over and over until an infected person's airways are besieged with billions of fast-spreading viral particles. In response, the body's immune system sends out an equally vast army of virus-killing white cells. It is the furious production of the white cells that creates the flu's fever, ache and lung congestion.
Chink in Armor
Once the Melbourne researchers saw the structure of the pocket and confirmed that it never changed, they knew they had found a chink in influenza's armor. "We quickly realized if we could synthesize a chemical to fit into the pocket and block the enzyme ..., we'd have a drug that could deactivate reproduction of every type of flu, no matter what strain," Dr. Colman remembers. By 1989, in collaboration with Biota Holdings Ltd., a Melbourne company created to exploit the discovery, the Australians had produced a drug -- now Rilenza -- that inhibited neuraminidase's activity without interfering with other human proteins. Biota licensed it to Glaxo.
Word of Rilenza's discovery and its ability to block the virus in test tubes arrived in a widely read research paper published in early 1993. But drug makers were skeptical that it was a viable solution. It needed to be given through an inhaler because when swallowed, the chemical couldn't get through the gut, into the bloodstream and to infected cells.
Researchers at Gilead Sciences in Foster City, Calif., were impressed by a 1994 report showing that Rilenza blocked transmission of the virus in mice. "We decided we might be able to make a pill" version, says Norbert Bischofberger, Gilead's research chief. By the end of 1995, Gilead had produced the experimental compound that would later be named Tamiflu.
Gilead and its partner Roche knew they were in a footrace with Glaxo, which had a huge lead. That's because Dr. Hayden in Virginia was already finding that Glaxo's still-experimental drug reduced viral levels in healthy human volunteers exposed to flu virus and then treated.
In an effort to catch up, Roche hired Dr. Hayden part-time to help it design studies. But both companies began to realize that doing the very large-scale human tests needed for FDA approval would be difficult -- a foreshadowing of the marketing challenges to come. "Because flu only occurs in the winter, and even then outbreaks are sporadic, we had to come up with some very creative ideas about how to test the drug," says Jonathan Solsky, Roche's medical-affairs director.
Following Outbreaks
Using CDC programs that track the flu as it pops up in the U.S., and drawing on similar public-health agencies in Europe and Australia, the companies set up testing sites at numerous medical centers to be ready if the flu surfaced in their areas. Then they looked for subjects. One newspaper ad from Roche asked: "Got the flu? This could be your lucky number." Call 1-800-I-Got-Flu, it said. The ad "was very effective in getting patients into the studies early," Dr. Solsky says -- a point not lost on company marketers.
Both companies' studies found that their drugs reduced a typical six-day flu bout by 30%, on average. Symptoms like muscle aches, headaches and congestion appeared about 40% less intense. It was clear that the sooner patients were treated, the better. Patients who take the drugs on Day 1 of getting symptoms have the best results, researchers say, but by Day 3, the drugs rarely work at all.
While both companies are cagey about the details of their marketing plans, discussions with executives and clinical investigators indicate a pattern will evolve: The companies, using the CDC and private testing companies, will identify where flu is prevalent. They will then dispatch sales representatives to doctors and pharmacists, alerting them that patients calling in are likely to have the flu. And in the U.S., they will at the same time blanket local airwaves and newspapers with ads, which will emphasize that patients must get to their doctors fast for the drugs to work.
And how to persuade doctors to choose Rilenza's oral inhaler version over the Tamiflu pill, or vice versa? That will be the subject of an entirely different set of ads -- and marketing techniques -- that is likely to inundate physicians throughout the coming flu season. |
