Despite Near Overwhelming Support, Concerns About Drug's Safety Continue
By Rita Rubin
WebMD Health News
Reviewed by Brunilda Nazario, MD
Feb. 22, 2012 -- An FDA advisory committee has reversed an earlier decision and voted overwhelmingly in favor of approving the weight loss pill Qnexa.
In August 2010, the panel rejected the drug 10-6. Although Qnexa had met FDA effectiveness requirements for weight loss drugs, clinical trials had raised concerns about its safety, specifically related to the heart and the risk of birth defects in babies whose mothers had taken it while pregnant.
In October of that year the FDA issued its negative decision in which it cited insufficient evidence of Qnexa's safety. In response, Vivus, the manufacturer, submitted final data for a one-year extension of one of its clinical trials.
Vivus proposes to market Qnexa to people who meet the government's definition of obesity: a BMI of 30 or greater. The labeling would advise people who lose less than 3% of their body weight in three months on the drug to stop taking it. The company will also put a plan in place to try and make sure pregnant women do not take the drug.
A final decision is expected from the FDA by April 17. Although the agency does not have to follow this recommendation, it often backs the decisions of its advisory panels.
Topiramate (sold as Topamax) has been linked to a higher risk of cleft lip and palate in babies whose mothers took the drug while pregnant.
FDA epidemiologist Suzanne Gilboa, PhD, presented information to the panel from two studies, one by Boston University and the other by the CDC, showing a small number of babies whose mothers had taken topiramate while pregnant. The only evidence of an association of birth defects was with cleft lip, Gilboa said. If the findings are true, she said, the risk for cleft lip in babies exposed to topiramate in the womb is 5 in 1,000 live births, five times the overall rate of 1 in 1,000.
FDA and Vivus representatives outlined plans for a "risk evaluation and mitigation strategy," or REMS. The drug would be dispensed only by certified mail-order pharmacies. Patients would receive a plain-language "medication guide" with each 30-day refill that emphasized the importance for women to use effective contraception while taking Qnexa.
Barbara Troupin, MD, head of medical affairs at Vivus, said the company would also establish a pregnancy registry of babies born to mothers who had taken the drug during pregnancy.
Doctor training would be offered but not required for those who want to prescribe Qnexa.
Heart Disease Risks
Clinical trials have shown that Qnexa has a favorable effect on most heart disease risks, including weight, blood pressure, HDL -- or "good"-- cholesterol, and progression to diabetes. However, the drug was shown to raise heart rate, which previous research has shown increases heart attack risk.
It's not yet known whether Qnexa's effects on heart disease risks will translate to a lower risk of heart disease. Panelist Michael Lauer, MD, one of the two "no" votes Wednesday, noted several other examples in which improved indicators for heart disease, such as cholesterol levels, proved to be misleading.
"I remember the cases of the anti-arrhythmic drugs. They were supposed to save lives, but they ended up killing people," said Lauer, director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute. Approval of Qnexa at this stage, he said, would be based on "hopes and suppositions."
But several speakers at the meeting's public hearing cited the need for more options for treating obesity. Joe Nadglowski, president and CEO of Obesity Action Coalition, which he described as a 35,000-member patient advocacy group, said there's "a significant treatment gap from Weight Watchers to (bariatric) surgery."
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SOURCES: Suzanne Gilboa PhD, epidemiologist, FDA.Barbara Troupin MD, head of medical affairs, Vivus.Joyce Weaver PharmD, senior drug risk management analyst, FDA.Michael Lauer MD, director, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute.Joe Nadglowski, president and CEO, Obesity Action Coalition.
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