REDUX ON THE ROPES

By Christine Gorman

The distinctive black-and-white sweater-striped pill was supposed to make millions of Americans thin--and its manufacturer rich. But a year after the drug called Redux was approved by the Food and Drug Administration for sale in the U.S., the hot new diet pill has fallen short on both counts. At $200 million a year, sales are flat and lagging far behind the initial $1 billion-a-year expectations. Some who have taken Redux have discovered that it is not the magic melting potion they hoped it would be; others who were thinking of taking it have been frightened off by stories about potentially harmful side effects--including a news report (later proved false) that a woman had died after taking Redux.

There is more bad news to come. Last month the FDA received a letter signed by several dozen neuroscientists blasting the agency for not opening up the post-approval monitoring process more fully. The FDA, these doctors charge, continues to ignore animal tests that suggest prolonged use of Redux can destroy nerve tissue. "Laboratories around the world have found that the drug has serious brain toxicity," says Dr. Mark Molliver of the Johns Hopkins Medical School. "It has the potential for producing brain damage."

In some respects Redux has been a victim of its own early success. The first new antiobesity medication in more than 20 years, the drug enjoyed one of the fastest launches in pharmaceutical history. Both the FDA and Wyeth-Ayerst Laboratories, which markets Redux, knew about the possibility of brain damage at high doses. But they also knew people who are morbidly obese--individuals who weigh 30% more than average--face even greater risks that they will die young from heart disease, diabetes or stroke. "We made the decision that the benefits outweigh the risks, at least for the population we identified," says Dr. James Bilstad, the FDA official who oversees drugs for metabolic disorders.

Still, the FDA was not entirely satisfied, and as a condition of approval it required that Wyeth-Ayerst conduct a follow-up study to determine whether Redux users were suffering any ill effects from the drug. Wyeth-Ayerst's critics say the company has been dragging its feet. Wyeth-Ayerst, for its part, says it is pleased with Redux's sales and is ready to start the tests, but that the FDA still has not decided how the study should be designed.

In the meantime, the drug has become a magnet for bad press--most of it unwarranted, if not downright false. In February, after the FDA met behind closed doors with officials from Wyeth-Ayerst to iron out details of the follow-up study, critics cried "cover-up"--as if the FDA never granted drug companies private meetings in order to protect trade secrets. In April the Associated Press reported that a 38-year-old, 120-lb. woman had died after taking Redux for just a few days. It turned out that she weighed 220 lbs. and was in fact murdered--a turn of events that can hardly be blamed on the diet pill. The AP issued a correction, but the damage to the drug's image had been done.

Bad press can, with time and a big enough marketing budget, be surmounted. Failing to deliver is another matter. "It just doesn't seem to work that well," says Dr. Richard Joseph, an obesity expert in Naperville, Ill. "I consider only a few of my patients Redux success stories."

Joseph is not sure why Redux has not panned out for more of his patients. It may be that they put too much faith in the pill to make them thin without their having to eat less or exercise more. But Joseph also suspects a biochemical explanation. Redux, like "fen/phen" before it, boosts the levels of serotonin, a neurochemical that, among other things, signals the brain that the body has had enough food. "If a lack of serotonin is the reason patients are overeating, then Redux should work beautifully," Joseph says. "But if they are overeating for some other reason, then it probably won't do any good. The question no one has answered is, What percentage of overweight people have low serotonin levels?" Such studies are impossible, experts say, without doing a biopsy on living brain tissue.

Meanwhile, competition is heating up. Last month an FDA advisory panel recommended approval of a drug called orlistat that works on the gut instead of the brain--reducing caloric intake by blocking the body's ability to absorb fat. Orlistat has its problems--its side effects include intestinal leakage. That doesn't mean orlistat will not be a big seller, at least at first. But if folks buy it expecting weight-loss miracles, they are bound to be as disappointed next year as Redux users are today.

--Reported by Lawrence Mondi/New York and Dick Thompson/Washington

With reporting by LAWRENCE MONDI/NEW YORK AND DICK THOMPSON/WASHINGTON