FDA Approves Phentermine-Topiramate Combo for Weight Loss

Vivus announced that the FDA has approved Qsymia capsules as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of >30 (obese), or >27 (overweight) in the presence of at least one weight-related comorbidity, such as hypertension, type 2 diabetes mellitus or high cholesterol (dyslipidemia).

Qsymia (formerly known as Qnexa) is the first once-daily combination treatment for obesity management. Vivus was required by the FDA to change the name of its product from Qnexa to Qsymia in order to avoid confusion with other similar-sounding drug names. It is a combination of phentermine, a sympathomimetic amine anorectic, and topiramate extended-release, an antiepileptic drug. Topiramate is thought to affect both appetite suppression and satiety enhancement.

The safety and efficacy of Qsymia were evaluated in two multicenter, Phase 3 trials that included severely obese patients (the EQUIP study), and overweight or obese patients with at least two weight-related comorbidities, such as hypertension, hypertriglyceridemia, type 2 diabetes, or central adiposity (the CONQUER study). The average weight loss in EQUIP was 10.9% on Qsymia 15mg/92mg and 1.6% for placebo (p<0.0001). The average weight loss in CONQUER was 9.8% on Qsymia 15mg/92mg, 7.8% on Qsymia 7.5mg/46mg and 1.2% for placebo (p<0.0001).

Vivus is also exploring Qsymia for type 2 diabetes and obstructive sleep apnea in phase-2 studies.

In February, an FDA advisory panel voted overwhelmingly in favor of the drug's approval for obesity, despite some concerns about possible adverse effects such as raised blood pressure and birth defects, as reported in the studies..

The agency then took the step -- not unusual in such cases -- of giving the company a three-month extension on the period during which it could review its application, which ended last Wednesday. That allowed the FDA to consider the Risk Evaluation and Mitigation Strategy (REMS) for Qsymia that Vivus had submitted on April 4.

Many on the advisory panel had stated that their vote favoring Qsymia -- it was ultimately 20 to 2 -- assumed that the company would in fact submit and implement a REMS, parts of which Vivus described at the hearing. That regulators granted an extension to facilitate that process was as good a sign as any that it was leaning toward a positive decision.

Both the FDA and its advisory committee had decided against approval of Qsymia on its first round of consideration in October, 2010, pending a more comprehensive assessment of its safety. Lorcaserin had followed a similar path in the premarket process, having been denied approval the same week for similar reasons; the agency approved lorcaserin just a few weeks ago.

Qsymia was approved with a Risk Evaluation and Mitigation Strategy (REMS) informing prescribers and female patients of reproductive potential about an increased risk of orofacial clefts in infants exposed to Qsymia during the first trimester of pregnancy. 

Qsymia (Schedule C-IV) will be available in 3.75mg/23mg, 7.5mg/46mg, 11.25mg/69mg, and 15mg/92mg dosage strength capsules in the fourth quarter of 2012.

News Release July 17, 2012