Anti-obesity drug wins recommendation from FDA advisory panel
May l4, 1997.
Xenical: Prices and Ordering Information
The first anti-obesity drug that does more than merely suppress appetite moved a step closer to the market Wednesday. Government advisers recommended approval of a pill that blocks the absorption of almost a third of the fat people eat.
But scientists cautioned that Xenical comes with embarrassing side effects that worsen with the more fat that dieters eat.
And taking the pill doesn't mean people can frequent McDonald's and still lose weight, manufacturer Hoffman-La Roche and outside scientists agreed.
Xenical may work by causing "a kind of intestinal aversion," said Dr. Jules Hirsch of Rockefeller University, before joining scientific advisers to the Food and Drug Administration in recommending approval of the drug. "Patients learn there are consequences to eating more."
Among side effects, Xenical can cause soft stools and oily leakages as the pill sends undigested fat out of the body so it doesn't wind up instead on dieters' thighs.
Xenical also can decrease absorption of vitamin D and certain other important nutrients, the panel warned. They unanimously recommended that Xenical users take carefully controlled doses of vitamin supplements.
The FDA isn't bound by advisory panel decisions but typically follows them. Metabolic drug chief Dr. James Bilstad said the agency would make a decision within a month.
Some 58 million Americans are overweight and spend $30 billion a year fighting the excess pounds, often futilely. Dieters have a variety of appetite suppressants that offer modest help.
The first new alternative in 20 years, Wyeth-Ayerst's hot-selling Redux, alters brain chemicals to trick the body into feeling full. A similar competitor, Knoll Pharmaceuticals' sibutramine, is expected to be approved within the year.
Xenical, known chemically as orlistat, would become the first drug to fight obesity through the intestine instead of the brain. The drug, taken with each meal, binds to certain pancreatic enzymes to block digestion of 30 percent of the fat people eat.
If Xenical is sold, no one should combine it with Redux or other appetite suppressants because there is no research to date showing that would be safe, warned Roche scientist Dr. Russell Ellison.
The FDA is evaluating how strongly to warn consumers and doctors about that issue, Bilstad said.
Two studies of about 1,400 patients found Xenical on top of a mild diet -- cutting about 600 calories a day -- helped obese people lose more weight in a year than people who took a dummy pill.
The weight loss was modest, scientists cautioned. On average, Xenical patients lost about eight more pounds than the dieters on placebo, or 5 percent to 10 percent of their initial body weight.
But when the patients went off their diets in the second year, those who kept taking Xenical regained only 26 percent of the weight they had lost while placebo dieters regained half of their weight, Roche said.
More intriguing, the FDA panel said, was that Xenical users also saw slight drops in their cholesterol, blood pressure and blood-sugar levels -- suggestions that the drug might lower the risk of heart disease that strikes so many obese Americans.
But eliminating undigested fat meant 26 percent of patients had "oily stools" and other gastrointestinal effects. About 20 percent of Xenical users had enough problems absorbing vitamins D, E and beta carotene that they were prescribed vitamin supplements. Vitamin D absorption is particularly worrisome, the FDA panel said, because it can lead to bone loss and osteoporosis, although Roche said studies so far don't show signs of that.
And the panel was perplexed by a handful of breast cancer cases. Ten women who took Xenical were diagnosed with breast cancer, while only one breast cancer case arose among female dieters taking a dummy pill.
Animal studies showed no evidence that Xenical caused cancer and half of the breast cancer was diagnosed so soon after the study began that FDA doctors and independent scientists said there didn't appear to be a link. Still, the advisers urged further study just to be safe and said Xenical should be labeled to warn about the puzzling finding.
"It's a little disconcerting that we're creating an illness of malabsorption in return for modest weight loss," said acting panel chairman Dr. Robert Sherwin of Yale University. But "we felt compelled to approve it" because of the effects on cholesterol and blood pressure.
LAURAN NEERGAARD
Associated Press Writer
