Miracle diet pill? A safe drug is elusive

To many, the FDA’s primary concern with Qnexa is perhaps even more frightening than fen-phen’s side effects: exposure to topiramate during pregnancy has been associated with a two- to five-fold increased prevalence of cleft palate in babies. Eisenson and others who spend their time helping severely overweight patients say that Vivus has a valid point—that these drugs also need to be viewed in perspective. Because for some patients, they say, the weight loss pills can work remarkably well. “In the hands of the right physicians and the right patients, they can be safe. There are people who need them—people who have tried everything else,” said Joseph Nadglowski, president of the Obesity Action Coalition. “We would be open to the FDA limiting distribution to make sure they go into those right hands to start, but the agency needs to take that balance into consideration.” The debate has raged for decades—beyond Qnexa and Xenical, even beyond the formation of the FDA. And unfortunately, its history is also one fraught with disaster, said Dr. Russell LaForte, a weight loss specialist at the University of Texas Medical Branch in Galveston, Texas. For more context on the FDA’s apprehensions, LaForte takes us through a number of those disasters, starting in the late 19th century. In September, a U.S. Senate committee directed the FDA to report in March “on the steps it will take to support the development of new treatments for obesity.” In October, the American Dietetic Association, the Obesity Society and two other medical organizations urged approval of the California drugs, saying all “had evidence supporting their efficacy.” Vivus claims one of its studies showed people taking a full dose of its new drug Qnexa for 56 weeks lost 37 pounds on average and all of the studies demonstrated “statistically significant” weight loss, the FDA has said.

Qnexa, an investigational drug to promote weight loss, has divided public health advocates, based on comments made Wednesday at a Food and Drug Administration advisory committee hearing. The advisory committee will vote later Wednesday in Silver Spring, Md., on whether to recommend approval of Qnexa, made by Vivus of Mountain View, Calif. The FDA will rule on the new drug application later this year, but it usually follows the advice of advisory committees.  An advisory committee of the Food and Drug Administration (FDA) recommended that the agency approve Qnexa, a combination pill of two existing drugs—the anti-seizure medication topiramate and the appetite suppressant Phentermine—to aid weight loss in clinically obese patients. The FDA often follows the recommendation of its advisory committees, but is not required to do so; the agency has until April 17 to make its final decision.  An advisory committee reporting to the Food and Drug Administration will, for the second time, hear evidence for or against the approval of Qnexa, which is a combination of two existing drugs—the anticonvulsant topiramate and the diet drug Phentermine—that promote weight loss. 

A federal advisory panel on Wednesday overwhelmingly backed Vivus Inc.’ s weight loss drug Qnexa, boosting the chance the could approve a new prescription weight loss drug for the first time in more than a decade.  The Food and Drug Administration has rejected three weight loss pills in the last two years, including Vivus’ pill Qnexa, due to safety concerns.

A FDA panel this week recommended that the weight loss drug Qnexa be approved for sale on the U.S. market. The pill is only for clinically obese people, and, if approved, would be the most effective legal, non-surgery weight loss method, with trial patients losing about 10% of their weight over a year, the drug manufactuer claims.  I’d add a few more notes of caution. Remember the REMS: Qnexa might not have been approved were it not for the advent of the Risk Evaluation and Mitigation Strategy (REMS), a relatively new way for the FDA to control how medicines are used once they are on the market. Sale of the medicine will be restricted to 10 mail-order pharmacies, with the goal of preventing women taking it from becoming pregnant and of telling people who don’t lose at least 3% of their weight during their first three months on the drug to stop. Investors should watch the actual structure of the REMS closely, because it could slow adoption of the drug. While it’s easy to come up with gargantuan sales estimates - one analyst told Bloomberg Qnexa could be the next Lipitor - no obesity drug has ever been a $1 billion seller.  A BMI of 25 to 29 indicates being overweight and 30 or greater is considered being obese. Dr. Elaine H. Morrato, assistant professor of health systems, management and policy at the University of Colorado, Denver, said she voted against approval of Qnexa in 2010 but decided to recommend approval this time because of the safeguards that will be put in place to monitor appropriate use and prevent problems. “I believe the FDA and the sponsor are striving to find the right balance between access to effective anti-obesity medications and the corresponding risks,” she said. People who don’t lose weight after three months on the drug would be encouraged to discontinue use because of its potential risks, experts said Wednesday. It’s likely that the first doctors to prescribe the medication would be those who specialize in obesity.

Several anti-obesity drugs remain in the pipeline, however. How they fare before the FDA may hinge on a meeting next month in which agency officials and pharmaceutical industry experts will discuss how to assess obesity drugs for cardiovascular safety. Several potential medications for obesity and other metabolic diseases have floundered because they raise the risk of heart problems even while causing weight loss. For weight loss drugs, side effects are a major issue. “Several potential medications for obesity and other metabolic diseases have floundered because they raise the risk of heart problems even while causing weight loss,” says Shari Roan at the Los Angeles Times.  With so few weight loss medications on the market and obesity at epidemic levels in America, the panel agreed that the risks posed by obesity outweighed the drug’s side effects.

Not all physicians are entirely in favor of Qnexa. In an article on the Huffington Post, Dr. David Katz writes that the approval was based in desperation to have more treatments for obesity in the market and that Qnexa likely isn’t safe for long-term use, because of its side effects. “It’s a bit harsh, I suppose, but I will nonetheless note that cocaine—another stimulant drug—produces weight loss, too. That doesn’t make it a good idea,” Katz wrote.  Vivus, the company that produces Qnexa, says that the drug has fewer side effects than other weight loss medicines. 

Qnexa “has the highest efficacy in terms of weight loss,” compared with other obesity drugs, said Sanjay Kaul, a professor in the David Geffen School of Medicine at UCLA Cedar Sinai Medical Center and a panel member, during yesterday’s meeting. “That shifts the balance in terms of requiring a post-approval study rather than a pre-approval study.” Patients that took Qnexa in studies lost 10 percent of their body weight on average, Vivus said on its website.  The FDA plans to have advisers discuss in March the possibility of requiring heart-risk studies for all weight-loss drugs. Panel members discussed whether Vivus should conduct such a study before or after approval. “Of all the obesity drugs, this one has the highest efficacy in terms of weight loss, so that shifts the balance in terms of requiring a post-approval study rather than a pre- approval study,” said Sanjay Kaul, a cardiology professor in the David Geffen School of Medicine at UCLA Cedar Sinai Medical Center and a panel member.  The panel ultimately was impressed by data showing a 10% weight loss at two years for people taking the drug. “Of all the obesity drugs, this one has the highest efficacy in terms of weight loss, so that shifts the balance in terms of requiring a post-approval study rather than a pre- approval study,” panel member Sanjay Kaul told Bloomberg News.