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2-Drug Combination Turned Down by FDA, but Company Plans to Try Again
By Kathleen Doheny
WebMD Health News
Reviewed by Laura J. Martin, MD
April 10, 2011 -- The experimental weight loss drug Qnexa produces a loss of up to nearly 10% of excess weight, according to a study just published in the Lancet.
The report published in The Lancet includes all the data that was already presented to the FDA last July by Vivus, the company developing the drug combination, Gadde says. However, he says, "this is the first time the data are presented in a peer-reviewed journal."
In July, an FDA expert advisory panel recommended against approval of Qnexa.
Since the rejection by the FDA advisory panel, the company has been addressing the concerns, says Peter Tam, the president of Vivus, which funded the study.
One concern is the use of topiramate, linked with birth defects such as cleft lip and cleft palate, by women who may become pregnant. Vivus is in discussion with the FDA now about how to address those concerns, Tam says.
"Our goal is to resubmit the new drug applications by the end of 2011," he says.
Qnexa: Study Details
For the study, researchers enrolled 2,487 participants, assigning them randomly to take either placebo pills or two different doses of the drug combination during the 56-week study.
In all, 2,448 patients were evaluated. This included 979 on placebo, 488 on the lower-dose regimen, and 981 on the higher dose. The lower dose included 7.5 milligrams of phentermine and 46 milligrams of topiramate. The higher dose was 15 milligrams of phentermine and 92 milligrams of topiramate.
To be eligible, patients had to have a body mass index of 27 to 45. No lower limit of BMI was in place for participants with diabetes. They also had to have two or more obesity-related conditions, such as high blood pressure or type 2 diabetes managed with lifestyle changes and/or the drug metformin.
Qnexa: Study Results
The average weight loss for those who completed the study was 28 pounds on the high dose, 22 on the low dose, and 4 pounds for those taking the placebo. The results meet criteria suggested by the FDA for weight loss products, Gadde tells WebMD.
Besides weight loss, Gadde tells WebMD, "this treatment led to significant improvement in excess weight-related diseases such as diabetes and high blood pressure and risk factors such as high cholesterol."
Those on the drug had a greater reduction blood pressure and improvement in so-called good cholesterol, HDL cholesterol, than those on placebo. Those who had diabetes at the study start and took the drug were less likely to need an increase in diabetes drugs than those on placebo.
"The most common adverse events were dry mouth, constipation, insomnia, and paraesthesia, which is a tingling sensation," says Gadde. He previously served as a consultant for Vivus but has not done so since 2008.
Concerns about the use of the drug combination by women who might get pregnant while on it were an issue for the FDA panel. In March, the FDA issued a warning about the use of topiramate during pregnancy, citing an increased risk of cleft lip and cleft palate.
When Vivus met with the agency in January, Tam says, the FDA asked if it would be possible to do an observational study using existing databases to evaluate the effects of topiramate during pregnancy.
"We expect to reach an agreement with the FDA in the next two months on whether this retrospective evaluation will be feasible," he says.
Since the end of the Qnexa trial, researchers have followed 675 participants for another year. They found that those in the higher-dose group had an average weight loss of 10.5% of their starting weight, those in the lower-dose group had 9.3%. Those in the placebo group had 1.8%.
Weight Loss Drugs: Perspective
The study itself reports no new information that the FDA has not already seen, says Frank Greenway, MD, an obesity researcher at Pennington Biomedical Research Center in Baton Rouge.
Its publication, therefore, won't likely change the minds of the advisory panel, which needs more information on the pregnancy-related risks.
Greenway says he is hopeful that Vivus can reach some compromise with the FDA.
"We desperately need drugs with which we can treat obesity," he says. Greenway has consulted for drug companies developing obesity drugs.
In January, the FDA turned down another weight loss drug, Contrave, which had won the approval of the FDA advisory panel, citing concerns about heart rate and blood pressure increases.
Another weight loss drug, Lorqess, was rejected last year by an FDA advisory panel.
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