Glaxo feels weight of regulators who'll rule on obesity drug
By Stephanie Saul The New York Times
WEDNESDAY, APRIL 26, 2006
NEW YORK When GlaxoSmithKline began talking to Roche three years ago about commercializing the prescription diet drug Xenical, the timing could not have been better for Steven Burton.
An executive with Glaxo's consumer heath care division, Burton had been overweight for years, carrying as much as 275 pounds, or about 125 kilos, on his 6-foot 1-inch, or 1.85 meter, frame. Those measurements put him on the edge of the "obese" category, a condition shared by one-third of Americans. And his doctor had just issued a stern warning to Burton.
"I didn't think seriously about a serious weight loss program until I had a couple of kids and I had a doctor who was telling me pretty bluntly that it was time to do something about my blood pressure and high cholesterol and weight for the sake of my kids," Burton said recently. "That's pretty motivating."
Now Burton, 47, has the job of motivator in chief as Glaxo prepares to market an over-the-counter version of Xenical. During the last three years, while ramping up the marketing effort, he has been using the drug himself.
And while he does not envision himself posing for the "before" and "after" shots in a diet ad, he can offer personal testimony to the drug's potential benefits. In his three years on Xenical, he says he has dropped to 210 pounds.
Those results, he warns, are better than the drug's typical user will achieve because he has combined Xenical with a rigorous regimen of exercise and diet. But he is counting on dieting success and good luck to carry over to the task of turning the drug into a successful over-the-counter weight loss product.
Xenical, introduced by Roche in Europe in 1998, has had only moderate success as a prescription drug in the United States, where it was introduced in 1999. The drug had about $500 million in global sales last year, only about 20 percent of that in the United States.
Part of the problem has been what Burton refers to as the "oops" factor - the drug's potentially socially embarrassing side effects. These can include diarrhea, flatulence and episodes of incontinence.
The drug's popularity also has been hampered by the only moderate, and sometimes fleeting, weight loss it typically yields, and the fact that many insurance companies do not cover its use. But Glaxo, which paid Roche $100 million and a promise of an undisclosed share of future revenue for over-the- counter rights to Xenical, is betting that Burton and his team can make a consumer version an attractive option for many of the two-thirds of Americans who are overweight. At stake is a piece of the estimated $15 billion annual market for weight-loss drugs and products.
"Even a small percentage of that market is going to be a significant commercial opportunity," said Burton, who is vice president for weight-control products for Glaxo's consumer health care division.
Burton already has a track record in such efforts. Although he never was a smoker, he led Glaxo's successful over- the-counter rollout of the stop- smoking products NicoDerm patch and Nicorette gum, which were sold only by prescription until 1996.
For Xenical, the Food and Drug Administration this month issued an "approvable" letter for over-the-counter sale of the drug, which Glaxo plans to market under the trade name Alli. Yet, while the company has said it expects the agency's final blessing later this year, the history of such migrations warns that approval is not assured.
Drug companies increasingly are turning to over-the-counter versions of their brands to extend the product life and generate steady cash flow. But for the FDA to clear a prescription drug for over-the-counter sales, it must be proved safe even when misused by careless consumers. It is not unusual to sink millions into a switch only to be shot down by the FDA. Merck and Johnson & Johnson learned that last year when an FDA advisory panel voted against their plan for direct sales of Mevacor, a cholesterol-lowering statin. Glaxo recently abandoned an idea to take the nasal spray Flonase over-the-counter, following speculation that the FDA would be reluctant to approve the commercial sale of a synthetic steroid-based spray.
The FDA approvable letter for over- the-counter Xenical means the product could fly, but the agency wants more information. It can sometimes take weeks, months, even years to answer FDA questions. Still, Burton said he is optimistic that Alli will be on drugstore shelves this year and at a price affordable to many Americans - $2 to $3 a day.
The gamble for Glaxo is particularly dicey given Xenical's marketing history. Despite its reputation as generally safe, and evidence that it helps people lose at least some weight, the product never became the blockbuster once envisioned.
Steven Francesco, who operates Francesco International, a pharmaceutical consulting business based in South Orange, New Jersey, said, "It never went very far on the prescription side, partly because they couldn't get reimbursement." Diet drugs are generally not reimbursed by insurance companies.
And image-wise, diet drugs carry tremendous negative connotations, as a category that has included some of the most colossal failures of the pharmaceutical industry.
Nearly 10 years after the drug Redux was withdrawn, for example, the maker, Wyeth, is only now drawing near the close of $21 billion in litigation over Redux - which was half of the diet combination known as fen-phen that was found to cause pulmonary hypertension and damage heart valves.
Xenical has a generally clean safety record. But the consumer watchdog group Public Citizen recently called for its withdrawal, citing research that some scientists say links the drug to colon changes that can be pre-cursors to polyp formation and cancer.
A Glaxo company spokeswoman, Malesia Dunn, said long-term testing in humans had demonstrated no increased risk of colon cancer in the drug's users. Raising another possible impediment, an FDA reviewer looking at the drug questioned whether there was any evidence the modest and transient weight loss experienced by Xenical users is a sufficient clinical benefit.
Despite Xenical's moderate success as a prescription drug, Francesco said that some lackluster prescription products have better potential on the over-the-counter market, where they can be sold in glitzy packaging on drugstore aisles rather than dispensed by a pharmacist in amber plastic bottles.
"There are a lot of marketing opportunities for this on the consumer side which aren't available on the prescription side," Francesco said.
Another industry marketing consultant, Guarav Kapoor of the New England Consultancy Group in Westport, Connecticut, said that Glaxo's understanding of the consumer market should not be underestimated. "Obviously, Steve's no dummy," Kapoor said. "He's got a whole group who's doing a lot of research on this."
At Glaxo, Burton envisions Alli's being sold at freestanding drugstore kiosks along with a colorful kit containing 250-page booklets offering advice on diet and including meal plans, calorie counters and dining-out guides. Consumers also would be able to sign up for a free online behavioral support program, with communications in the form of e-mail newsletters and chat rooms where people can trade stories of their diet successes and lapses.
Already, the company has started an interactive Web site, QuestionEverything.com, where dieters can post comments and take part in surveys, an advance look at what the Web-based marketing might look like, even though the site makes no overt reference to Xenical or Glaxo.
Full details of the Alli rollout plans have not been released. But if past is prologue, here's a clue: Shortly after the introduction of the company's Nicorette and NicoDerm, Glaxo's NicoVan traveled the country advising patients on how to quit smoking. The products quickly grabbed 90 percent of the $575 million smoking cessation market.
With Alli, Burton said, "mobile counseling or health-fair counseling is going to be a very important part of the way we reach out and talk to consumers." Emphasizing that the drug is not a magic pill, Burton said the company would look for committed consumers ready to make long term changes in the way they eat and exercise.
Burton also said the campaign will very clearly warn consumers about the drug's side effects. The flatulence, diarrhea and uncontrollable oily discharges are problems that become worse when the drug is taken along with a high-fat meal.
"I'll never forget having a fish sandwich and loading it up with tartar sauce and having French fries," Burton recalled. "I actually discharged some oil." Luckily for Burton, what he refers to as his "classic oops" episode happened on a Saturday when he was doing errands, not during an important meeting. So he went home to change clothes.
The drug works by blocking the absorption of fat in the intestine, meaning that about one-third of the fat a user eats is never absorbed but instead excreted through stool - the reason a high-fat diet can cause uncontrollable releases. By restricting the amount of fat intake, a user can control those excretions to some degree.
The recommended diet is a moderately-reduced calorie intake, restricted to about 3o percent fat. Although a surer route to weight loss might be a diet even lower in fat, a stringent low-fat diet would make the pill largely superfluous.
So Glaxo's approach will emphasize discipline, rather than deprivation. For example, consumers taking Alli would be instructed that, when eating at an Italian restaurant, chicken Marsala is a better choice than stuffed manicotti.
The big questions are whether, with all the competing diets, foods and programs, Glaxo can generate enough interest in Alli and, even if so, whether the product will have staying power.
"You can guarantee it will be a full army of effort," said Francesco. "Weight reducers tend to be passionate and then burn out, then they go to the latest and greatest. This could hit a potential $500 million a year, then sink like a stone."
One reason for doubt is that, in a Glaxo study of patients taking Xenical at over-the-counter dosage, about 3 percent quit because of the side effects.
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