By Marie Daghlian
Just days after denying approval of Arena Pharmaceuticals' (ARNA) lorcaserin to treat obesity, the U.S. Food and Drug Administration notified Vivus (VVUS) it would not approve its application to market its experimental obesity drug Qnexa (phentermine/topiramate) without additional information. Vivus had sought approval to market Qnexa as an oral, once-a day pill to treat obesity in patients who are obese or overweight with co-morbidities such as hypertension and diabetes.
The FDA wants a comprehensive assessment of the drug's potential to cause birth defects and asked for a detailed plan and strategy to evaluate and mitigate the potential risks of birth defects in women of childbearing age who take the drug to lose weight. The agency also asked Vivus to provide evidence that the elevation in heart rate associated with phentermine/topiramate does not increase the risk for major adverse cardiovascular events.
In order to better assess the long-term safety of Qnexa, Vivus was also asked to formally submit the results from its already completed 52-week extension study for a subset of 675 patients who completed the previously reported 56-week study. Vivus announced top-line results from the two-year study in mid-September and is preparing a final report for submission to the agency.
Although the FDA did not request any new clinical studies, it asked for a safety update of any new adverse events be submitted. Finally, the FDA stated that if approved, Qnexa would be designated as a controlled substance because phentermine is a component of the drug. Phentermine was a component of the diet drug Fen-Phen, which was pulled off the market in 1997 when it was shown to cause potentially fatal pulmonary hypertension and heart valve problems.
Vivus plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the risk of potential birth defects of topiramate. In addition, Vivus plans to comply with all of the agency’s requests and says it remains confident that it will be able to satisfy them and get the drug approved. The company said it is preparing a comprehensive response to the FDA and will submit it in about six weeks.
About one-third of American adults, more than 72 million people, are obese, and many more are overweight with co-morbidities. Unfortunately, the search for a magic skinny pill has yet to bear fruit. Orexigen’s (OREX) investigational obesity treatment Contrave is set to be reviewed by regulators before the end of the year.