For the second time in as many weeks, the FDA has approved a diet drug -- phentermine/topiramate (Qsymia). The two approvals follow a 13-year-long drought in the prescription diet drug pipeline.
Formerly known by the brand name Qnexa, the drug was approved for as an addition to a weight-loss program that includes both calorie restriction and exercise. Moreover, the FDA said the drug's use should be limited to in patients with a body mass index (BMI) of at least 30, or a BMI of 27 with at least one other weight-related comorbidity such as diabetes or hypertension.
In approving the drug, FDA signaled its intent that the drug's use be tightly controlled. For example, the drug's label will include a number of contraindications, and Vivus, the company that is marketing the drug, will be required to complete 10 postmarketing studies, including a long-term cardiovascular safety trial to assess effects on major events including MI and stroke.
Additionally, the FDA is requiring a risk evaluation and mitigation strategy (REMS) for the drug.
In its announcement, FDA said the drug is contraindicated during pregnancy because topiramate has been shown to increase the risk of oral clefts among newborns.
It's also not for use in patients with glaucoma or hyperthyroidism, the FDA said, noting that the drug also has the potential to increase heart rate and is not recommended in patients with recent or unstable heart disease.
The road to approval for the drug, once known as Qnexa, has been long and bumpy -- Vivus filed a new drug application in 2009, but that initial application was rejected in 2010 after an FDA advisory committee recommended against approval, largely over concerns about psychiatric and cardiovascular side effects.
When Vivus resubmitted its application with new analyses, the same advisory committee voted 20 to 2 in favor of approval this past February, with the stipulation that the company conduct a large postmarketing study to clarify the cardiovascular risks.
In the company's latest attempt, the FDA originally set an approval deadline of April 17, but then requested a revised REMS, which the company didn't submit until April 4.
Given that the submission was a major amendment to the marketing application, the FDA was permitted to extend its review period, changing the deadline to July 17.
A second weight-loss agent, lorcaserin (Belviq), was approved on June 27, making it the first such drug to enter the anti-obesity market in more than a decade.
It, too, was approved for patients with a BMI of 30 or more, or 27 and up with at least one obesity-related comorbidity.
Lorcaserin, made by Arena Pharmaceuticals, was also initially turned down by the FDA in 2010, largely due to concerns about valvular heart disease.
Arena was also asked to conduct postmarketing studies, including a long-term cardiovascular outcomes trial looking at major events such as MI and stroke.
Experts say Qsymia appears to be more effective than lorcaserin, with weight reductions of up to 9% for patients on the highest dose of the drug (15 mg phentermine, 92 mg topiramate).
FDA noted that patients on the combination agent who don't have effective weight loss by 12 weeks are unlikely to benefit, so therapeutic response should be evaluated by that time.
Chatter about the approval of Qsymia came hours before FDA gave its official word, as USA Today accidentally published online a prepared story of the drug's approval.
The story was immediately removed from the paper's website, but reports said it quoted extensively from Vivus executives and doctors about the approval.