February 27, 2012
By Mark Hyman. M.D.
This week, in an act of desperation to turn back the tide of the obesity epidemic that now affects almost seven out of every 10 Americans and more than 80 percent of some populations (African-American women), the advisory committee to the Food and Drug Administration (FDA) voted 20 to 2 to recommend approval of Qnexa, a “new” obesity drug that is simply the combination of two older medications, phentermine (the “phen” of phen-fen”) and topiramate (Topamax).
It is a misguided effort at best, and a dangerous one at worst. Mounting evidence proves that the solution to lifestyle and diet-driven obesity-related illnesses including heart disease, diabetes, dementia, and even cancer won’t be found at the bottom of a prescription bottle.
By 2020, more than 50 percent of the U.S. adult population will have Type 2 diabetes or prediabetes, with annual costs approaching $500 billion. By 2030, total annual economic costs of cardiovascular disease in the U.S. are predicted to exceed $1 trillion. By 2030, globally we will spend $47 trillion, yes trillion, to address the effects of chronic lifestyle-driven disease.
Prescription medication for lifestyle disease has failed to bend the obesity and disease curve. Statins have been recently found to increase the risk of diabetes in women by 48 percent. And large data reviews by independent international scientists from the Cochrane Collaborative found that statins only work to prevent second heart attacks, not first heart attacks, which means they are not helpful and most likely harmful for 75 percent of those who take them.
Avandia, the No. 1 blockbuster drug for Type 2 diabetes, has caused nearly 200,000 deaths from heart attacks since it was introduced in 1999. The drug was designed to prevent complications of diabetes, yet heart attacks are the very disease that kills most Type 2 diabetics. In 2011, the FDA issued stricter prescribing guidelines for Avandia, but the drug is still on the market.
The large ACCORD trial found in more than 10,000 diabetics that intensive blood-sugar lowering with medication and insulin actually led to more heart attacks and deaths.
Something is deeply wrong with our medical approach.
The problem of chronic disease, including obesity, diabetes, and heart disease, is not a medication deficiency, but a problem with what we put at the end of our fork.
The emperor truly has no clothes. Why would good men and women of science vote to approve a medication for a condition that is a social disease and requires a social cure? The social, environmental, economic, and political conditions of America and increasingly the global community have created an obesogenic environment.
Clearly we need to do something. But it is not better medication or surgery or more angioplasties and stents, which have no proven benefit in more than 90 percent of those who receive them. The data show they work for acute coronary events, but not stable angina or blockages.
We continue to pay for expensive treatments for chronic disease, despite the fact that they don’t work, while insurance does not pay for nutrition counseling unless the patient has kidney failure or diabetes.
Chronic disease is a food-borne illness. We ate our way into this mess and we must eat our way out.
February 17th, 2012
By: Carrie Gann
In the search for treatments to fight obesity, regulators are turning their attention to a diet drug that has already failed to receive government approval as a weight loss treatment.
Next week, a panel of advisors to the U.S. Food and Drug Administration will consider whether or not to recommend the diet drug Qnexa for approval. The move is the latest attempt to give new tools to patients and doctors to fight the obesity that currently plagues one-third of Americans. It also fans a fiery debate about the search for a “magic bullet” alternative to difficult lifestyle changes to help obese people lose weight.
Qnexa was rejected by the FDA in 2010 over concerns about potentially dangerous side effects, such as cardiovascular problems and birth defects. Now, the FDA will consider whether or not the drug’s manufacturer, Vivus, should do a larger clinical trial to investigate the potential for cardiovascular side effects.
But some obesity specialists are, in effect, already giving the drug to their patients by prescribing Qnexa’s two major ingredients, phentermine and topiramate. The practice, called off-label prescribing, is not prohibited by the FDA. Doctors who have prescribed this combination say it has helped patients shed pounds when many other paths to weight loss have failed.
Dr. Ken Fujioka, director of the Center for Weight Management at Scripps Clinic in San Diego, said he often sees obese patients who have changed their diets, started exercising more and still have not been able to lose more than a few pounds. Though bariatric surgery is a lasting, effective option for long-term weight loss, many patients either aren’t morbidly obese enough to qualify for the surgery or are reluctant to resort to such a drastic measure to lose weight. For about 30 of these patients, Fujioka has prescribed low doses of phentermine and topiramate.
“The weight loss with this combination rivals bariatric surgery and I see using these meds in the seriously obese patient as an alternative,” Fujioka said.
Dr. Jana Klauer, a New York City-based doctor specializing in weight management, said her patients lost an average of 40 pounds when taking the drugs along with improved diet and exercise plans.
“The drug combination gives great results, providing diet and exercise are part of the plan,” she said.
Vivus, the company that developed Qnexa, said in a statement that the drug is a combination of low doses of both drugs and it is intended for use in combination with improvements in diet and exercise. Vivus said it does not support the off-label use of phentermine and topiramate.
The drugs work by suppressing appetite, and both have been approved by the FDA for other uses. Phentermine, a stimulant, is already approved for weight loss, but only for short-term use. Topiramate is an anticonvulsant, for which weight loss is a side effect.
But a laundry list of side effects has many experts concerned about the safety of the drugs, if taken over a long period of time. Topiramate creates feelings of mental fogginess, memory lapses and a lack of concentration.
Phentermine, one of drugs that made up the failed diet drug Fen-Phen, can lead to a range of cardiovascular side effects, such as high blood pressure, heart attacks and heart palpitations. Dr. David Katz, co-founder of the Yale University Prevention Research Center, noted that these side effects are the very problems caused by obesity.
Dr. Charles Clark, a professor of pharmacology and toxicology at Indiana University, said the potential side effects are enough to keep him from prescribing phentermine and topiramate to his patients, particularly in light of the failure of Fen-Phen, which was withdrawn from the market in 1997 after causing fatal blood pressure and heart valve problems in patients.
“Given our experience with Fen-Phen, we should be cautious in our use of these agents until larger and longer-term trials are completed,” Clark said.
Others say concerns about side effects of both drugs and their offspring Qnexa are legitimate, but could be managed or avoided if doctors carefully monitor patients while they’re taking the drug. For example, the FDA’s concerns about potential birth defects caused by Qnexa could be resolved by not prescribing the drug to women who could get pregnant. Many doctors say the risks of these drugs may be outweighed by the benefits for some patients with disabling health problems caused by obesity.
In the past 20 years, a parade of diet drugs have come before the FDA, representing an effort by drug companies to give obese patients and their doctors alternatives to difficult, often unsuccessful lifestyle changes. Most of the drugs have failed to meet the agency’s standards for safety and effectiveness. Many come with a list of embarrassing side effects, such as anal leakage, and only one, Alli, is approved for long-term use. A handful of drugs, such as Metabolife and Meridia, were removed from the market because of heart safety concerns.
Some doctors say there is no evidence that Qnexa will perform better than the diet drugs that have already flopped.
“I have made selective use of some weight loss drugs, but have not to date found much reason for enthusiasm for any of them,” Katz said. “I don’t have much for Qnexa.”
Others are more hopeful that Qnexa is different, including Dr. Chip Lavie, medical director of cardiac rehab and prevention at the Ochsner Clinic Foundation in New Orleans. He cites evidence from previous clinical trials that Qnexa helps patients lose a modest amount of weight, which improves their risk factors for diabetes, high blood pressure and other cardiovascular problems. He said cardiovascular and birth defect risks that the FDA cited in its first look at the drug were very slight and “clinically unimportant.”
“Considering the dismal results that many experience with attempted weight loss with diet and exercise, which is always the first choice, and the explosion in the need and use of bariatric surgery, this combination drug should be a major advance, and I hope that it gets approved this time by the FDA,” Lavie said.
For The Full Report Go To ABC News
July 14, 2010
by Matthew Perrone
Dieters, doctors and investors get their first extensive look at the first of a trio of new weight loss drugs this week. The hope is that the new drugs can succeed where many others have failed: delivering significant weight loss without risky side effects.
With U.S. obesity rates nearing 35 percent of the adult population, expectations are high for the first new prescription drug therapies to emerge in more than a decade. Even a modestly effective drug has blockbuster potential.
None of the three medicines represents a breakthrough in research. Drugmakers have made little headway in understanding and treating the causes of overeating. Two of the drugs submitted for approval simply combine existing drugs — an anticonvulsant and an amphetamine — but have worrying side effects. The third, a new medication, is safer but less effective.
The quest for a blockbuster weight loss drug has been plagued for decades by safety issues. The most notable was Wyeth’s diet pill drug combination fen-phen, which was pulled off the market in 1997 due to links to heart valve damage and lung problems.
The FDA is expected to post its review of Vivus Inc.’s pill Qnexa on Monday and will hold a public meeting Thursday to review the data. Orexigen Therapeutics Inc.’s Contrave is set for review in October, and Arena Pharmaceuticals Inc.’s lorcaserin is set for December.
“There’s no obvious clear winner,” said Leerink Swann analyst Steve Yoo. “If you look at different aspects, each drug shines.”
To be considered effective, obesity drugs should reduce total body weight by at least 5 percent after one year, according to FDA guidance to companies.
Qnexa showed the best weight loss results in clinical trials, with patients losing between 13 percent and 15 percent of their body weight. But the drug also had the highest rate of patient dropouts due to side effects, which include memory and concentration problems.
Qnexa is a combination of two older drugs: the amphetamine phentermine and topiramate, an anticonvulsant drug sold by Johnson & Johnson as Topamax. According to the company, phentermine helps suppress appetite, while topiramate makes patients feel more satiated.
Contrave is also a combination pill, mixing an antidepressant with an anticonvulsant drug. The drug has shown weight loss between 5 percent and 10 percent with side effects such as nausea.
University of Liverpool Professor Jason Halford said drug companies are taking a multi-pronged approach to obesity therapies because science has shown there are multiple brain signals that drive food intake.
“We’re using combinations of old drugs with a very broad spectrum of pharmacotherapy, it’s very much the shotgun approach,” said Halford, a health psychologist who has consulted for drug companies on obesity treatments.
The one truly novel drug under FDA review showed the weakest results in clinical trials. Arena Pharmaceuticals’ lorcaserin is a first-of-a-kind drug that acts on serotonin, a brain chemical associated with feelings of well-being and satiation. But patients in company trials lost just 5 percent of their body weight.
While Arena’s drug trails its competitors in weight loss, it appears to have the least side effects, an important factor in FDA approval.
Investors clearly favor Vivus in the three-way race. Shares of Vivus have nearly doubled over the past year to close Friday at $11.52.
Arena Pharmaceuticals shares have fallen nearly 4 percent over the past year on lackluster results for its drug. Orexigen shares have fallen 21 percent over the past year, to close Friday at $4.17, marking a bouncy descent from a June 2007 peak of $17.70 a share.
Decision Resources, a drug industry analysis firm, believes all three drugs could eventually win approval and find a place in the global obesity market. The firm expects the global market to soar from $500 million to $3.4 billion a year by 2018.
Still, the history of diet drugs is littered with stumbling blocks.
The diet drug fenfluramine, which was half of the fen-phen combination, was withdrawn in 1997 after it was linked with heart damage. The drug’s combination with phentermine was popular but never approved by FDA.
Two years ago Sanofi-Aventis SA discontinued studies of its highly anticipated pill Acomplia due to psychiatric side effects, including depression and suicidal thoughts.
Side effects have kept the small number of weight-loss drugs currently on the market from being blockbuster sellers. Abbott Laboratories’ appetite suppressant Meridia was pulled from the market in Europe last November due to data showing increased heart attack risks. And in May, the FDA warned consumers that the over-the-counter weight loss pill alli, which has been sold for years at a higher dose as the prescription drug Xenical, could cause severe liver damage. The drug works by limiting the amount of fat the body can absorb.
Derek Lowe, a pharmaceutical researcher and blogger, says the new combination drugs under review hold promise because they work on multiple brain chemicals that drive overeating.
“No single agent is going to shut down this behavior,” said Lowe, whose blog “In the Pipeline” focuses on drug development. “But if you can come in and hit two or more of these different pathways at the same time, maybe then you’ll get somewhere.”