Posted Tuesday, July 3, 2012, at 10:00 AM
Photo by Justin Sullivan/Getty Images
Last week, the FDA approved the first new prescription weight-loss drug in 13 years. Belviq, which sounds more like a brand of mineral water than a diet pill, has been OK’d for obese patients and for the severely overweight with at least one obesity-related condition, like hypertension or diabetes.
The weight-loss benefits are extremely modest. Compared to placebo, over the course of a year of dieting and exercise, patients taking Belviq lost an average of 3 to 3.7 percent of their initial body weight. A 200-pound patient could expect to lose an extra 6-7 pounds on Belviq, but she would have to keep taking the drug for the rest of her life to keep it off. The manufacturers of Belviq recommend that patients stop taking the drug if they don’t lose at least 5 percent of their body weight in the first 12 weeks.
The FDA rejected Belviq in 2010 because of unanswered questions about cardiovascular side effects and the drug’s propensity to cause cancer in rats. To allay the FDA’s cardiovascular concerns, Belviq’s manufacturer, Arena Pharmaceuticals, sponsored huge trials in which thousands of patients taking Belviq, or a placebo, received regular echocardiograms to see if the drug was harming their valves. The FDA panel concluded Belviq was safe enough to go on the market, but recommended an extensive post-marketing study to rule out cardiovascular complications. Which is … comforting?
The FDA won’t require patients on Belviq to get regular echocardiograms, but Dr. Eric Felner, a member of the FDA advisory panel that approved the drug, told the panel that in his opinion, “If you're going to put your patient on this medication, you need to see them somewhere along the lines of every two to three months and probably get an echocardiogram at least two or three times a year.”
Arena’s stock price has more than quadrupled in the last two months based on rising expectations that the drug would be approved, and some analysts are predicting that Belviq could bring in a billion dollars a year. So, why all the excitement over a drug that produces less weight loss than a good behavior-modification program?
Some physicians hope that Belviq will be a safe replacement for fenfluramine, the “fen” in fen-phen. Fen-phen was a combination of the serotonin-booster fenfluramine and the stimulant phentermine. Neither drug produced much weight loss on its own, but combined they were superstars.
Fen-phen was a blockbuster. In 1996 alone, doctors wrote some 18 million prescriptions a month. This was the Holy Grail of long-term obesity treatment.
The risks of fen-phen, of course, didn’t become apparent until after the drug was on the market. The FDA belatedly estimated up to a third of patients using fenfluramine or dexfenfluramine developed heart valve damage. Fenfluramine was subsequently withdrawn from the market in 1997. Phentermine is only approved for short-term weight loss.
Belviq is supposed to be safer than fenfluramine because it acts on just one serotonin receptor found almost exclusively in the central nervous system, whereas fenfluramine stimulated serotonin activity indiscriminately, including serotonin receptors on the heart valves. Belviq has never been tested in combination with phentermine, but some weight loss doctors already have big plans for a fen-phen revival.
“I know that some of you are afraid that the clinicians will combine [Belviq] with phentermine,” Dr. Ed Hendricks, a weight loss physician, and a member of the FDA advisory panel that approved Belviq, told the panel in May. “You have to remember that the motivation behind developing this drug was developing a replacement for fenfluramine that was safe.”
Hendricks went on to explain that if Qnexa, a weight-loss combination of phentermine and an anti-convulsant currently in the pipeline, is approved, many clinicians will consider that de facto proof that phentermine is safe in long-term combination therapy and take it as a green light to prescribe a Belviq/phentermine cocktail. Hendricks didn’t mean this as a warning, but rather as something to look forward to.
Patients should remain skeptical. Off-label prescribing is a dirty little secret of the pharmaceutical industry. Pharmaceutical companies often seek approval for a narrow indication, knowing that doctors can and will prescribe the drug much more widely. Obesity medicine is full of frustrated doctors and desperate patients, demographics that have historically been easy pickings for snake oil salesmen. Our advice: Don’t buy the hype.