Is the diet-pill binge ending?
It was only a little over a year ago that a potent new appetite suppressant burst on the scene, greeted joyously by legions of Americans weary of dieting. Doctors greeted Redux warmly too, as did storefront diet clinics. Redux and an existing but newly popular drug combo called "fen-phen" were bright with promise, for consumers, clinics and drug companies alike.
Side-effect reports were lurking about the edges, but seemed manageable. Now, that has changed dramatically. The side effects are center stage.
Alarmed by word of heart-valve problems with fen-phen and a crippling or fatal lung condition with Redux, some health-maintenance organizations are beginning to restrict coverage of the drugs. Patients are quitting clinical trials meant to measure their long-term effects. A new report from a market-research firm called IMS America tells the tale: From peak levels in February, weekly prescriptions for Redux have plunged 52% to 44,175. Weekly prescriptions for fenfluramine, the "fen" in the fen-phen combination, have collapsed 63% to 55,718.
"People are so fearful that they want no part of the drugs. The decline is absolutely off the charts," says Robert Nierman, a surgeon who opened one of the first diet centers in Massachusetts to offer the fen-phen combination. "We're fighting for survival now."
For the drugs' makers, the trend is worrisome. Analyst David Crossen of Montgomery Securities in San Francisco had predicted Redux sales would eventually reach $1 billion a year. "All the signs looked like this was going to be an extraordinary product," he says. "It was the fastest launch of a drug ever. In the first 11 weeks it hit an annualized sales rate of $220 million." Now Mr. Crossen sees annual sales of the drug sinking to perhaps the $70 million level, indefinitely.
The worst could be yet to come. IMS's report on falling prescriptions covered the week ended Aug. 22. Since then, articles in the New England Journal of Medicine and the Journal of the American Medical Association have further highlighted the risks. The JAMA article said the drugs, taken in doses comparable to those prescribed to human dieters, caused brain damage in monkeys and rats. In a rare step, the New England Journal called for a moratorium on use of the drugs by those not seriously overweight.
Some chains of weight-loss centers, including Jenny Craig Inc., are abandoning both Redux and fen-phen. Other clinics that focused almost exclusively on diet drugs have shut down, including two in the Miami area.
Redux marketer American Home Products Corp. of Madison, N.J., concedes that sales, which were $132 million in 1996 and were rising earlier this year, have recently dropped off steeply. But an official says, "We continue to see significant interest in the product and will do whatever we can to make sure patients who are obese and need this drug are prescribed it." The company will do studies on whether the drugs cause either brain damage or lung disorders.
American Home Products also makes and markets fenfluramine, under the brand name Pondimin; 1996 sales were $173 million. The other part of the fen-phen combination, phentermine, is sold under different brand names by several firms. Drugs identical to Redux and Pondimin have long been sold in Europe, and American Home estimates that 50 million people world-wide have taken them.
Though American Home markets Redux, the drug's developer and manufacturer is Interneuron Pharmaceuticals Inc., of Lexington, Mass. It wouldn't comment, but a founder did. Richard Wurtman, a Massachusetts Institute of Technology professor whose brain-chemistry research in the 1970s led to Redux, maintains the drug is safe and thinks the scare will be short-lived. "In the end, truth will win out and Redux will have a major impact on obesity in America because it works and it's safe," Dr. Wurtman says.
The drugs are a small part of American Home's business, and its stock hasn't been hurt by the health scare. But Interneuron shares have fallen more than 50% from a high of $44.50 in April 1996.
The controversy comes just when many medical experts believed safe and effective drug therapies were at hand for a condition that afflicts one-third of the nation's adult population. About 60 million Americans tip the scales at 20% or more above ideal weight, making them more susceptible to heart disease, diabetes and high blood pressure. About 300,000 U.S. deaths each year are thought to be obesity-related.
Many dieters raved about Redux and fen-phen, which work by tinkering with a brain chemical called serotonin, the same one affected by the antidepressant Prozac. Terry Hamilton-Wollin, a 50-year-old shipping agent in Tampa, Fla., was delighted when she dropped to 129 pounds from 154 after beginning a fen-phen regime last year.
But then this July, the Mayo Clinic said 24 healthy patients had developed heart-valve disease after taking fen-phen. The Food and Drug Administration issued a public warning. Ms. Hamilton-Wollin dropped the "fen" part of the combo, and she has added weight. "I'd have to be a complete idiot to continue on after watching the news and seeing what dreadful things are happening to people," she says. She now uses an herbal therapy.
Some obesity experts fear the scare will cause long-term damage to the notion of treating obesity with drugs. About 40% of 300 patients enrolled in a long-term UCLA study of fen-phen have dropped out in the past three months because of concerns about side effects, even though a UCLA doctor says the four-year, soon-to-be-published study has found no evidence of serious side effects.
Also potentially hurt are the prospects of new diet drugs, working differently, that await FDA approval or are in late-stage clinical trials. "I'm afraid the problems are going to cause a setback in the approval of new agents and in the development of new agents," says Michael Steelman, president of the American Society of Bariatric Physicians, or obesity specialists. "People are so quick to become judgmental in the area of obesity."
Hopes for treating obesity through new drugs first were raised in 1992 following the publication of a four-year University of Rochester, New York, study, sponsored by the National Institutes of Health, of 121 patients who took fen-phen. The study showed the patients lost weight rapidly over six months and sustained the loss for up to four years.
Thousands of doctors soon began prescribing the combination therapy, even though it wasn't sanctioned by the FDA. Clinics — dubbed "pill mills" by critics — sprang up across the country, and ads promoting fen-phen for quick and easy weight loss appeared in local newspapers.
"There are some clinics that will give a prescription without examining or even seeing a patient," says Peter Vash, executive medical director of Lindora Inc., a privately held chain of weight-control clinics in California. Concerned Florida authorities have been drafting rules to halt such abuses by requiring that patients be given thorough medical exams by doctors before the drugs are prescribed.
But "the people who really jumped on the bandwagon in terms of offering these drugs were the individual physicians, especially the membership of the American Society of Bariatric Physicians," says John LaRosa, research director at Marketdata Enterprises Inc. in Tampa, Fla. Membership in the society, which doesn't endorse specific drug therapies, tripled between 1995
and 1997 as some doctors, hurting financially in the era of managed care, turned to the hot new field of obesity treatment. Mr. LaRosa estimates 11,000 doctors were writing prescriptions for fen-phen and Redux as of last year.
Many traditional weight-loss clinics, which emphasize a nutritionally balanced, calorie-controlled diet and exercise, didn't sit idly by. In August 1995, Nutri/System LP, a private chain in Horsham, Pa., began offering fen-phen at some of its centers. By this summer, nearly 300 of its 500 clinics were offering "medical weight-loss services," says Joseph DiBartolomeo, a vice president.
Some weight-loss chains may have felt they had little choice. "People were flocking to their doctors rather than the commercial diet centers," Mr. LaRosa says.
But as word of rare but serious side effects grew, so did concern about potential liability. (American Home already faces more than one suit over Redux.) The legal concern pushed weight-loss chains in the other direction. Jenny Craig is advising physicians in its centers to discontinue prescribing Redux and fen-phen immediately. "As a result of these actions, the company no longer offers any medical adjunct," says the La Jolla, Calif., company. It estimates that 700 of its 70,000 clients were taking the medications.
A Bit of Prozac? Nutri/System says it is now recommending that clients using fen-phen and Redux -- it won't say how many there are -- switch to a new combination dubbed "phen-Pro" -- phentermine and Prozac. "Phen-Pro works differently than fen-phen, but it still suppresses your appetite and helps you lose weight ... without the risk," Dr. DiBartolomeo contends. However, Morton Maxwell, co-director of the obesity center at the University of California at Los Angeles, says: "There's no evidence that giving Prozac with [phentermine] will enhance its efficacy. There is no such study."
Diet Workshop Inc., a Boston-based chain of 50 centers throughout New England, says it has stopped giving new patients Redux and fen-phen, in part because of concerns about liability. "There's so much controversy right now," says President Gail Montgomery. "We're afraid it could smear our good name, so we've decided to hold off until the medical community decides yeah or nay."
Elsewhere in Massachusetts, entrepreneur Andrew Rudnick, who scraped together $40,000 last November to start one of the state's largest chains of diet centers, is seeing patients flee because of the health scare. As recently as six months ago, his Medical Weight Loss Center chain had 7,000 patients. Now he has 2,200. He has closed one of his six centers.
The clinics no longer use fen-phen and are cutting back on Redux. "Because of the scare, most of our patients are using natural herbal products such as ephedra," Mr. Rudnick says. Dubbed "nature's fen-phen," the herb is reputed to raise serotonin levels and suppress appetite. "It's not nearly as effective as the prescription, and none of this works without diet and exercise," he adds.
Some HMOs are reviewing or changing their policies about paying for diet drugs. Joseph Gerstein, in charge of pharmacy benefits for Tufts Health Plan in Waltham, Mass., says the organization will ask physicians to allow only patients who have experienced significant weight loss to remain on the drugs. Otherwise, he says, "the hazards are too great." In January, the northeast division of Kaiser Foundation Health Plan stopped paying for Redux because of safety concerns.
FDA ApprovalRedux was approved in April 1996 only after two heated hearings of the FDA's advisory committee. Concerned about side effects, the panel initially voted to reject the drug. At a second meeting, it voted narrowly to recommend approval. Members were swayed largely by the feeling that obesity, epidemic in America, was causing unneeded deaths.
"I think our decision to approve Redux was justified at the time. It was approved based on the benefits and the risk," says James Bilstad, director of the FDA's office of drug evaluation.
Today, the FDA says it doesn't yet know what it will do about Redux, but hasn't ruled anything out. Asked if the agency might revoke approval, Dr. Bilstad says, "We're obviously following the situation very closely. We're reviewing reports as they come in. We're discussing options available internally, but I'm not going to state what options we're discussing."
Being carefully scrutinized are reports of "adverse events" sent by physicians to the agency about patients taking diet drugs. To date, the FDA has reports of about 70 cases of heart-valve problems and another 70 cases of primary pulmonary hypertension. The agency must determine whether the side effects are caused by the drugs, Dr. Bilstad says.
Last year, the FDA revised Redux's label to reflect a higher-than-previously-thought risk of pulmonary hypertension. The condition occurs in somewhere between 23 and 46 people for every million who take appetite suppressants, according to a large study published last year in the New England Journal of Medicine. In the general population, the lung disease has an incidence of one to two people per million. Redux proponents contend the benefits outweigh the risks because diet drugs can save hundreds of lives for every million obese patients who take them.
'Black Box'In July, the FDA issued an advisory on potential heart-valve problems and will now require a prominent "black box" on Redux and Pondimin packages warning of possible heart and lung complications.
The agency was to have considered two major new experimental diet drugs for approval. But one of them, Xenical, was temporarily withdrawn last week by Swiss-based Roche Holding Ltd., which cited the FDA's concerns about a possible link between the drug and breast cancer. Roche said it needs to analyze its research and may have to sponsor more clinical trials.
The other drug, sibutramine, made by the Knoll Pharmaceutical Co. unit of Germany's BASF AG, isn't expected to be approved until year end, according to the company. Data presented to the FDA found that sibutramine increases blood pressure and heart rate slightly on average.
Such findings are likely to cause additional concerns among the overweight. Keith Van Gasken, of Lynn, Mass., says he is quitting fen-phen this week because of fears of its possible side effects, even though he considers the drugs a "marvel" that helped his weight drop to 195 pounds from 270 pounds in 19 months.
American Home warns against writing Redux off, pointing out that such a blockbuster drug as Prozac also once hit a rough patch. The company will continue educating physicians about the fact that "obesity is a chronic illness that requires treatment," says an official, Mark Dietch, and may eventually take its message directly to the public. "We're evaluating all options at this point," Dr. Dietch says.
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