July 18th, 2012
FDA Approves Another New Weight Loss Drug
Larry Husten, PHD
The US FDA approved on Tuesday a new weight loss drug that will be called Qsymia, the brand name for the combination of two previously approved drugs, phentermine and extended-release topiramate. The drug is manufactured by Vivus, Inc.
In a press release, the FDA said Qsymia had been approved for use in obese adults (BMI of 30 or above) or in overweight adults (BMI of 27 or above) with at least one other weight-related condition, such as hypertension, diabetes, or dyslipidemia.
The label recommends a daily dose of Qsymia containing 7.5 mg of phentermine and 46 mg of extended-release topiramate. The drug will also be available at the higher dose of 15 mg of phentermine and 92 mg of extended-release topiramate.
According to the FDA, in clinical trials, at 1 year, patients taking the recommended dose had an average weight loss of 6.7%, while those taking the higher dose had an average weight loss of 8.9%, when compared with patients taking placebo. People taking the lower dose of Qsymia who do not lose 3% of their body weight after 12 weeks are unlikely to achieve a sustained weight loss on the same dose. These patients should either discontinue the drug or move to the higher dose. After 12 weeks on the higher dose, people who do not achieve a 5% weight loss should discontinue the drug.
The combination drug is contraindicated during pregnancy. Because of the high risk for oral clefts in fetuses exposed to topiramate, women should have a negative pregnancy test before starting Qsymia and every month while taking the drug, in addition to using contraception. The drug is also contraindicated in people with glaucoma or hyperthyroidism. Because the drug may increase heart rate, its use in people with recent or unstable heart disease or stroke is not recommended. In addition, the FDA recommends that all patients taking Qsymia have their heart rate monitored regularly, in particular when starting the drug or increasing the dose.
FDA is requiring Vivus to implement a Risk Evaluation and Mitigation Strategy (REMS), consisting of a Medication Guide for patients and a plan to educate prescribers and patients to avoid the increased risk for birth defects associated with the drug. Pharmacies will need to obtain a special certification before dispensing Qsymia. The FDA is requiring the company to perform a long-term cardiovascular outcomes trial.
The drug had previously been known as Qnexa, but was forced to change the name by the FDA “because too many other drugs ended in the same letters and it would have caused confusion,” Vivus President Peter Tam told Bloomberg News.
The approval of Qsymia, along with the approval a few weeks ago of Arena’s lorcaserin (Belviq), are the first new weight loss drugs approved by the FDA since 1999.
5 Responses to “FDA Approves Another New Weight Loss Drug”
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This drug seems to come with a large number of side effects based on the EQUIP study published last year in the journal Obesity -19% developed parasthesia; 17% developeded dry mouth, 14% develop constipation, 12.3% developed URTI.
Also, the dose approved for initial clinical use (7.5/46) was not the dose studied in the trial (3.725/23 dose and 15/92 were reported on).
Thus (and I am just wondering about this as a fellow interested in the process and this is not a critique)-
(a) How does the FDA weight the risk/benefit in deciding on a drug like this?
(b) How does the FDA determine dosage recommendations (akin to the dabigatran dosing decision from a year ago)? Is unpublished data considered?
John– Sanjay Kaul, who was a member of the FDA advisory panel that reviewed this drug, sent the following response to your questions:
The efficacy assessment of Qsymia was primarily based on 3 Phase III clinical trials. EQUIP or OB-302 study was one of them which explored weight loss efficacy of low (3.75/23) and high dose (15/92). The middle dose (7/46) was explored in other 2 phase III trials: OB-301, and OB-303 (plus OB-305, 2 year extension study of OB-303). Placebo-subtracted mean weight loss was 3.2%, 6.7% and 8.9%, respectively, for the low, mid and high dose. The low dose does not meet the more stringent 5% mean weight loss criterion for obesity drugs. There was numerically greater reduction in SBP and DBP and lower increase in hear rate with the mid dose c/w low dose. Noncardiac side effects (paresthesias, constipation, dry mouth, cognitive effects, acidosis, etc.) were seen with higher frequency with the high dose. Thus, based on the totality of data, the middle dose of Qsymia has optimal benefit-risk profile.
The FDA bases its decisions on the primary data submitted by the sponsor. Quite often these data include results from studies that are either unpublished or not published in their entirety.
Approval of 75mg dose of dabigatran was based on pharmacometric (PK/PD) modeling studies that is generally accepted to provide reliable dose estimates.
Hope this is helpful.
Perfect. That is very helpful and insightful. Thanks
Not to be unduly cynical, but I wonder what the jury will decide in the first malpractice case involving this drug.
It would be most prudent to wait till this drug has been on the market at least 5 years before even thinking of prescribing this drug. This would help both the Dr.(malpractice wise) and the patient(safety) from the side effects that only appear once the drug hits the market. The know side effects of this drug are enough to scare me off