This week’s big news is the potential arrival of Qnexa, the first new obesity drug to head for tentative FDA approval in 13 years. (The last, Xenical, hit the market in 1999.) Of course, there’s good reason for that; numerous weight loss drugs have been found to have dangerous side effects, causing the FDA to reject them. In fact, Qnexa itself was rejected by the FDA in 2010. So what’s up now?
So far, the story’s mainly being reported as a business story. And that it certainly is; the stock of Vivus, Inc. the Mountain View-based pharmaceutical upstart that created Qnexa, jumped 98 percent today in its first day of trading after the FDA panel’s 20 to 2 vote. Given past sales figures for diet drugs, Vivus can expect to make a boatload of cash on Qnexa and shareholders will smile all the way to the bank. One analyst predicted the drug could be the “next Lipitor,” resulting in millions of prescriptions.
But what about the people taking it? How long will they be smiling?
In terms of weight loss, Qnexa will likely produce smiles. Clinical data (not yet published) showed participants lost an average of 10 percent of their body weight, according to Vivus’ claims. But as Robert Carlisle’s Mr. Gold loves to say on the TV hit Once Upon a Time, “All magic comes at a price.” What’s the price to your overall health of taking Qnexa?
Let’s start with what’s in the drug. Qnexa is actually a “cocktail,” meaning it’s a combination of two previously FDA-approved drugs, phentermine — an appetite suppressant — and topiramate, an anti-convulsant.
If you feel like you’ve heard the name phentermine before, you have - it’s the “phen” from the notorious diet drug cocktail of the 1980s, Fen-Phen, withdrawn from the market for damaging heart valves. Technically a contraction of the chemical name phenyl-tertiary-butylmine, phentermine has a similar pharmacology to amphetamine and works by suppressing appetite.
Because it works by triggering the release of catecholamines, phentermine is known to have two heart-related side effects: tachycardia (increased heart rate) and elevated blood pressure. These side effects don’t happen with the frequency and severity that they do with amphetamines, but patient complaint boards are full of people posting messages about worrisome spikes in heart rate and blood pressure and resulting heart palpitations.
Here’s how nurse Patricia Nevins describes it: “Phentermine hydrochloride affects the cardiovascular system in much the same way that fear, excitement and anger do. Essentially an amphetamine, phentermine stimulates the part of the central nervous system that regulates the heart and blood pressure. Physicians prescribe phentermine hydrochloride as part of a weight-loss program because of its ability to increase metabolism and suppress the appetite. The cardiovascular effects of phentermine can cause serious heart problems.” I couldn’t have put it any better myself, hence the quote.
It’s important to understand that phentermine is a very old drug, available for more than 40 years. And topiramate has been around for ages, too. What that means in terms of the FDA approval process is that both drugs are considered to be already approved, so less new testing is required than would be for a brand new formulation. However, when phentermine came under fire as part of Phen-Fen, some studies were undertaken to try to understand which drug might have caused the heart damage. While the studies seemed to indicate that phentermine wasn’t the primary culprit, they didn’t exonerate the drug either because it was extremely difficult for researchers to tease out the data.
The FDA is concerned enough about heart problems from Qnexa that they are considering requiring studies – but the studies might come after the drug hits the market and people begin taking it. With two other diet drugs, Contrave and Arena, also in the pipeline for FDA approval, the FDA plans to have advisers discuss the possibility of requiring heart-risk studies for all weight-loss drugs.
According to the NIH’s backgrounder on phentermine, those with even moderately elevated blood pressure, hyperthyroidism, and “excitability” should avoid the drug. Perhaps more germane for those trying to shed pounds, the NIH warns that the phentermine’s “anorectic” effects last only a few weeks, and cautions against increasing the dosage when the drug loses its effectiveness on weight loss. But what do you want to bet that patients, happy to see the pounds peeling off but frustrated with the plateauing effect, will ask their doctors to increase the dosage and at least some doctors will comply to continue the weight loss success?
Now on to topiramate. The active ingredient in Topamax, topiramate causes a fairly high incidence of confusion, memory loss, concentration problems, and “psychomotor slowing” resulting — among other things — in difficulty finding the correct words. According to the NIH, Topiramate also carries warnings for depression and mood problems, fatigue and “somnolence” (sleepiness). And then there’s that pesky “suicidal ideation” – talk about a permanent side effect. While these side effects aren’t considered as serious as heart damage, they’re significant and the incidence is surprisingly high; 42 percent of those taking topiramate reported one or more cognitive or mental problems. In addition, pharmacology reports found that babies born to mothers who took topiramate were found to have a higher incidence of cleft palate.
As to the combination of the two drugs together? It’s a bit of an unknown. While Vivus registered four Stage III clinical trials with the government registry, no study results from any of those trials have been published, though presumably preliminary data were submitted to the FDA panel. At least, let’s hope so.
I guess what I’m trying to say here is that if you take Qnexa, you’re essentially allowing yourself to be a bit of a guinea pig in the watch for side effects, just as the early takers of Phen-Fen did.
In the panel meeting two days ago, members discussed whether Vivus should conduct further studies before or after approval. The FDA is due to decide on Qnexa by April 17. For its part, Vivus is asking to start a four-year trial of the affect of Qnexa on cardiac health after the FDA votes whether or not to approve the drug on April 17th. Is it just me, or does that seem bit backward?
Melanie Haiken, Contributor