Expert Panel Advises FDA Approve Qnexa for Obesity Treatment

Yesterday, the US FDA Endocrinologic and Metabolic Drugs Advisory Committee voted 20 to 2 in favour of approving Qnexa, a low-dose controlled-release formulation of phentermine and topiratmate, for the medical treatment of obesity.

This is the first positive vote for a new anti-obesity drug by the FDA committee in 13 years.

As I pointed out in my presentation (on behalf of the sponsor) to the Advisory Committee , Qnexa has the potential to address an important unmet clinical need – both the degree of weight loss (just over 10% on average) and the favourable trends in cardiovascular risk factors (with the exception of heart rate) have the potential of making this a significant advance in our ability to medically manage obesity.

As I told the Committee,

“Back in medical school, I was taught that when the risk of not treating a condition exceeds the risk of treating, then you treat.”

As readers of these pages know, there are indeed substantial health risks with not treating obesity in those who have evident obesity related health problems.

Not that there are no risks with treatment – based on the experience with the use of topiramate as an anti-epileptic drug and for the prevention of migraines, there is a likelihood that the topiratmate component in Qnexa (although contained at a lower dose) can increase the risk of orofacial clefts if taken during the first trimester of pregnancy – this is why, it is likely that the drug will not be freely available and there will be strict measures in place to minimize exposure in women, who may become pregnant. (discussion around this issue included a rather funny moment, when one of the panel members, asked how often you could expect the average ‘Joe’ to take a pregnancy test – this was quickly corrected to average ‘Jane’)

But there are also other risks like kidney stones, tingling in hands and feet, and perhaps some psychiatric issues that may need to be carefully monitored.

In this context it is important to remember, that at the recommended dose, Qnexa contains only about a quarter of the maximum dose of phentermine (30 mg) and less than one-eight of the maximum dose of topiramate (400 mg). The lower risk for side effects with these substantially lower doses is additionally mitigated by the controlled-release formulation.

This is probably why many of the common ‘side effects’ commonly associated with topiramate (e.g. memory and attention problems), were not a major issue in the Phase III studies. rather trial participants reported significant improvement in all aspects of quality of life, including physical functioning, self-esteem, sexual life, public distress, and work.

Obviously, it is important to remember that all participants in these trials (including those in the placebo group) also received comprehensive lifestyle education together with a 500 kcal calorie reduction.

While Qnexa is unlikely to work for everyone (there were about 25% non-responders in the trials), for patients who respond and tolerate this drug well, it may be a substantial step forward in managing their excess weight.

The strong positive vote of the Advisory Committee is not binding to the FDA, but it is highly likely, that the drug will eventually be approved.

It will certainly be most interesting to see how these benefits in clinical trials will translate into clinical practice once Qnexa hits the market.

AMS
Washington, DC

Disclaimer: I am a consultant to Vivus Inc, the maker of Qnexa