Oct. 39, 2010— -- WASHINGTON -- The FDA has declined to approve the investigational weight-loss pill Qnexa, marking the second time in a week the agency has rejected a diet drug.
The FDA wasn't expected to approve the medication because a panel of outside experts voted in 10-6 in July against recommending approval for the combination drug -- made by Vivus -- which was shown to be effective in helping obese and overweight patients lose an average of 6-10 percent of their body weight in the company's clinical trials.
At the meeting, one panelist said the drug is "far superior to anything on the market;" however, concerns over psychiatric and cardiovascular issues uncovered in the company's trials ultimately trumped the weight-loss benefit.
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Vivus was seeking approval for a once-daily pill for obese men and women with a body mass index (BMI) of 30 or higher, or in overweight patients (those with a BMI of 27 or higher) who also have weight-related health problems such as hypertension, diabetes, dyslipidemia, or central adiposity.
The drug combines low doses of two approved drugs: phentermine, an appetite suppressant that was the most widely prescribed obesity drug in 2009, and topiramate, an anti-seizure medication that increases the feeling of being full and satisfied.
While both agents are known to carry their own health risks, combining them in lower doses mitigates many of those risks, Vivus argued.
Psychiatric adverse events -- including sleep disorders, anxiety, and depression -- occurred in 21 percent of patients taking the highest doses of the new drug, compared with 10 percent of patients taking placebo.
Cardiovascular safety was also a prominent concern, largely because half of the combination is phentermine, a component of Fen-Phen, the popular fenfluramine/phentermine obesity drug that was pulled from the market about six months after its approval in 1997 because of an increased risk of heart valve problems.
Data from the company's trials didn't indicate an increased risk of valvulopathy, although the drug did increase heart rate.
In its decision letter to Vivus, the FDA requested that Vivus provide evidence that the elevation in heart rate does not increase the risk for major adverse cardiovascular events, according to a press release from the company.
The FDA also requested a more comprehensive assessment of Qnexa's potential to cause birth defects. During the FDA advisory committee meeting, the panel was concerned about a lack of data on the possible link to birth defects if a woman were to become pregnant while taking the drug.
In an animal study testing its teratogenicity, craniofacial malformations were detected in baby rabbits and rats. And in a U.K. study in humans that tested topiramate only, there were three cases of similar malformations.
In the company's trial, 34 women became pregnant, despite being required to commit to using two forms of birth control and to submit monthly pregnancy tests. Thirteen of those women gave birth, and no birth defects were detected, but some panel members were still concerned about approving a drug that would likely be used by millions of women of childbearing age.
Vivus said it will respond to the FDA within six weeks and provide new analyses that show Qnexa does not increase the risk for major cardiovascular events.
"We remain confident in the efficacy and safety profile of Qnexa demonstrated in the clinical development program and look forward to continue working with the FDA towards the approval for the treatment of obesity," said Leland Wilson, chief executive officer of Vivus, in a prepared statement.
Less than a week ago, the FDA notified Arena Pharmaceuticals that it will not approve the company's investigational weight loss drug lorcaserin, in part because data from animal studies suggest that lorcaserin increased the risk of mammary adenocarcinoma in rats.
Early in October, the maker of the obesity drug Meridia voluntarily agreed to remove it from the U.S. market because of increased risk of stroke and myocardial infarction.