The nearly unanimous recommendation of a 22-member FDA expert panel to rescind a prior decision and approve the weight loss drug Qnexa says something about the FDA, something about Qnexa, something about obesity, something about those suffering from obesity and most of all, something rather profound and quite ominous about our society.
About the FDA: No doubt, some will applaud and some will vilify the FDA if if it follows the advice of its expert panel, as it should, and approves Qnexa. Some will see the heavy hand of big pharma at work -- and, indeed, Vivus, the maker of Qnexa, had by all accounts lobbied pretty hard for this outcome.
But approval of Qnexa will represent the FDA doing its job, not some great scandal. The FDA raises and lowers the bar for approving drugs based on what else is available. A drug, for instance, that treats a life-threatening condition for which no other drug is available is likely to be approved, even if potentially quite dangerous. The drug just has to be less dangerous and more effective than having no drug at all.
At the other end of the spectrum, a drug may be quite effective and relatively safe, but disapproved if there are many other drugs to treat the same condition that are even nominally safer and/or more effective.
In other words, the FDA is constantly weighing risks and benefits. Nothing in medicine, and little in life, is entirely free of risk. Risk is justified by the potential benefit. Risk is also justified if it is a means of avoiding an even greater risk, which would, in fact, count among the benefits. A fairly dangerous drug or procedure may be the best option to treat an even more dangerous cancer or cardiac condition. Effective chemotherapy for acute leukemia can be quite toxic -- but less so than the leukemia itself. An intra-aortic balloon pump is no walk in the park, but it beats cardiogenic shock.
There is, at present, only one FDA-approved drug for weight loss, and it isn't very good. Other weight-loss drugs that have been approved at some point no longer are. The most promising drug of all in my opinion, rimonabant, was never approved in the U.S. because it meaningfully increased the risk of suicide. Qnexa did not have to be very good or very safe to produce 20 thumbs up. It just had to be better than... nothing.
About Qnexa: The drug, in fact, isn't very good. True, it does produce a weight loss of roughly 10 percent of body weight over a year or two in clinical trials, and does outperform placebo -- but so does every weight-loss drug ever tested.
Qnexa is a combination of two drugs, phentermine and topiramate, and frankly I don't much like either of them. Phentermine is an amphetamine-like stimulant, and very unlikely to be safe or suitable for long-term use. Among its common side effects is an elevation of blood pressure -- one of the complications of obesity itself. We gain little if a treatment causes the complications of the condition that we are treating to avoid such complications...
It's a bit harsh, I suppose, but I will nonetheless note that cocaine -- another stimulant drug -- produces weight loss, too. That doesn't make it a good idea.
Topiramate is an anti-seizure drug. It can, and often does, cause fatigue, brain fog and nausea. It is generally a bit difficult to get patients with epilepsy to keep taking such drugs because they often don't feel very well on them. But the risk of a grand mal seizure is a very potent incentive. It's hard to imagine anyone remaining on such a drug to keep off weight they have lost -- and history indicates clearly that if and when the drug is stopped, the lost weight is likely to be refound.
The FDA panel recommended approval of QNEXA only because so many of us are so heavy, and the ranks of useful weight loss drugs are so thin -- and desperate times call for desperate measures. Approval of QNEXA would reflect that... desperation.
About obesity: The approval of a not-very-good drug tells us a couple of things about obesity itself. First, it tells us that obesity remains a largely intractable problem, crying out for new solutions. Second, it tells us that after decades of trying, a not-very-good-drug is the best that big pharma, with all its resources, can do. It is quite reasonable to ask: Why?
We have developed potent treatments for cancer, heart disease, diabetes, infections, stroke and almost every other condition we might add to the list. Why can't we come up with one for obesity?
I have an answer. You would, I trust, expect that a fish with an infection could be treated with an antibiotic. But I also trust you would not expect any medicine to fix the problem of a fish out of water. There is nothing a pill could do, short of turning a fish into something other than a fish, that could fix the "out-of-water" problem. And obesity is just like that.
Just as it is normal for a fish to breathe in water and asphyxiate out of it, it is normal for humans to turn a surplus of calories into an energy reserve, namely, body fat. It's very hard to fix what isn't really broken.
What is broken -- for a fish out of water, and for humans drowning in calories and labor-saving technology, is the link between the creature and the habitat that nurtures it. You can save the fish -- just not with a pill. Throw it back in the water. More on that below.
About those with obesity: Vivus' intense interest in having the FDA revisit their prior decision about Qnexa, and the support of the FDA panel for approval, both suggest that there will be a market for this drug. If nothing else, it will serve as a potential alternative, at times, to bariatric surgery.
This tells us that many people with obesity are overwhelmed. They cannot fix the problem with the resources at their disposal, and they are desperate for any new option -- even an option that combines an amphetamine with an epilepsy drug. The victims of epidemic obesity need help they aren't getting, and will accept it even in the form of a pill you couldn't pay most people to take!
About our society: The most important message is here. Our search for a drug to treat obesity is testimony to a profound societal failure to address the root causes of the obesity epidemic.
A half century ago, there was dramatically less obesity. Very little about genes, metabolism or human nature has changed in the past five decades. We have epidemic childhood obesity now; we did not have it then. The ambient level of "personal responsibility" in 8 year olds has not changed over that span.
A dramatic change in the epidemiology of obesity is directly related to profound changes in our environments, food supply, activity levels and social norms. We have caused the obesity epidemic, by looking the other way as a staggering array of "advances" made ever more calories ever more temptingly available, and made physical activity ever more elusive.
The root cause and cure of all but rare cases of obesity resides with how we use our feet and forks. Pharmacotherapy is no substitute.
It's no substitute because it tends not to work well. It's no substitute because it comes at high cost, in dollars and side effects. It's no substitute because of the fish-out-of-water problem; drugs don't fix that. And it's no substitute, because we have epidemic obesity among adults and children alike. Do we envision the Qnexa family pack? If not, while adults are taking their drugs, what, exactly, will the kids be doing?
We cannot simply call for better use of feet and forks in a world that conspires mightily against them. We must pave the way, so health is achievable along a path of lesser resistance. We can demand personal responsibility, but we must also make sure people are suitably empowered to take responsibility for their health and the health of their families.
The problem we confront is a large flood of obesigenic factors. The solution must be like a levee. No one thing will fix this mess. No one idea, no one policy -- and certainly no one wonder drug. Every empowering program, policy and resource we make available is a sandbag in the levee. We can turn the tide, one sandbag at a time. But we will do so when, and only when, the levee tops the height of the flood.
I worry, though, that we will fail to do so as long as we keep holding out for that wonder drug. I worry that we won't commit to the fundamental solutions we need while preoccupied with pharmacotherapy and fantasies about quick and effortless fixes. I worry that we will neglect the right recipe in a futile search for the one "active" ingredient.
We can fix this mess -- safely, universally and decisively. But it won't be quick, and it won't be effortless. Few worthwhile things ever are.
There is, indeed, a role for pharmacotherapy for obesity -- as there is a role for surgery. But it should be a small role, because overwhelmingly, the problem can and should be fixed with feet and forks. It should be a small role because of the high monetary and human costs of anatomy-altering operations and potentially toxic drugs. Those who need these options should certainly have access to them, and for that reason, I don't protest the likely approval of Qnexa per se.
What I protest is any indulgence in the idea that this is a meaningful solution to the problem of epidemic obesity. I protest the attention and resources that get diverted from making the modern environment more salutary, more conductive to healthful use of feet and forks. As a society, we should be doing all we can -- and we are not! -- to make sure very few of us ever need the options of surgery or drugs.
FDA approval of Qnexa will represent a rather desperate measure at a desperate time for desperate individuals of a desperate society. So be it. But our desperate need to address this problem decisively is long overdue, and should be the mother of far better invention than this.
-fin
Dr. David L. Katz; www.davidkatzmd.com
www.turnthetidefoundation.org
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