Americans spent an estimated $59 billion last year fighting fat – on weight-loss programs, special foods, low-calorie soft drinks, appetite suppressants, gym memberships, diet books, exercise videos, even stomach-clamping surgery.
But less than 1 percent of that sum, as estimated by the research firm Marketdata Enterprises, was spent on prescription drugs. Despite years of research effort – and haunted by diet drugs that proved dangerous, like fen-phen in the 1990s – the pharmaceutical industry has not made meaningful progress in combating obesity, one of the nation’s biggest and costliest health problems.
Now, though, three small California companies hope to succeed where many bigger players have failed. The companies – Arena Pharmaceuticals, Orexigen Therapeutics and Vivus – plan to apply in the coming months for regulatory approval of anti-obesity drugs that could reach the market in late 2010 or in 2011.
With about one-third of American adults gauged to be obese, and another third overweight, a successful drug could garner billions of dollars in sales, even as it potentially reduced the nation’s overall medical bill.
A recent study conducted partly by the federal Centers for Disease Control and Prevention estimated that treating obesity and diseases caused by it cost as much as $147 billion in 2006, or 9 percent of all health care spending.
“This is the biggest field, bigger than statins potentially”, said Jack Lief, chief executive of Arena Pharmaceuticals, referring to cholesterol-lowering drugs like Lipitor, which by itself had $12.4 billion in global sales last year.
The companies say they have tried especially to avoid side effects that have tripped up diet drugs in the past. And the products from Orexigen and Vivus are combinations of two drugs, which some experts say might be more effective than a single medicine.
Patients in clinical trials of the three drugs lost an average of 3 to 10 percent of their weight after a year in addition to what was accomplished by efforts to improve diet and exercise.
Vivus’s drug, Qnexa, provided the greatest weight loss, which is why that company’s stock is up 90 percent this year, more than that of the other two companies. But Qnexa’s ingredients may raise the biggest safety questions, although the clinical trials did not detect major problems.
Some experts say the weight loss provided by the drugs is modest, and in some cases is no better than that of existing drugs. Still, if the new drugs prove safer they could nonetheless help millions of people.
“I really believe that for the first time we’re going to have some real options,” said Dr. Ken Fujioka, director of the weight management center at Scripps Clinic in San Diego and a consultant to various pharmaceutical companies.
But the potential and the pitfalls are illustrated by the history of fen-phen, a combination of diet pills.
When word spread that the combination was effective, prescriptions soared to 20 million in 1996, up from three million in 1994, according to Cory Kasimov, an analyst at JPMorgan. But the next year, two of the drugs used in the combination were withdrawn from the market because they caused damage to heart valves, leaving the drug maker Wyeth with about $21 billion in liability.
Safety is a big concern for obesity treatments because the drugs might be taken for many years, and by many people who might be otherwise healthy, except for their weight. What is more, people who are not even obese might also want the drugs, a vanity issue that rarely comes into play for treatments aimed at, say, diabetes or hypertension.
“I think what the F.D.A. is going to be paranoid about is a non-obese person who wants to drop 5 or 10 pounds in front of a wedding or a reunion,” Mr. Kasimov said.
The new drug candidates work through the central nervous system to influence appetite, and the F.D.A. has said it is particularly concerned about possible psychological side effects of such drugs.
For example, rimonabant, a Sanofi-Aventis drug once viewed a surefire blockbuster, failed to win F.D.A. approval in 2007 because of links to depression and suicidal thoughts. The drug, also known as Acomplia, was then taken off the market in Europe. And Merck and Pfizer abandoned their efforts to develop drugs with a similar mode of action.
Even drugs that have made it to market have not done well. IMS Health, which tracks prescriptions, estimates combined sales of obesity drugs last year at only $173 million in the United States. According to IMS, about 75 percent of the 6.8 million diet prescriptions last year were for phentermine, a 50-year-old generic stimulant that was an element in the fen-phen combination but was not taken off the market.
Experts say the two name-brand diet drugs now on the market have suffered from limited effectiveness – a weight loss of about 5 percent, typically – and potentially significant side effects. Meridia, sold by Abbott Laboratories, can increase blood pressure and heart rate, while Xenical, from Roche, can cause flatulence and embarrassing loss of bowel control. A lower-dose version of Xenical, called Alli, is available without a prescription from GlaxoSmithKline.
The pharmaceutical industry’s learned wariness of obesity drugs is a potential problem for the three small California companies, all of which are hunting for a big pharmaceutical company to help market their products.
Developing an effective weight-loss drug is also difficult because the body is almost hard-wired to maintain its weight, experts say. As many dieters know, as weight goes down, appetite can go up.
“You push a lever down in one spot and something else seems to come up in another spot” said David B. Allison, director of the clinical nutrition research center at the University of Alabama at Birmingham. “It’s hard to suppress the system dramatically for long periods of time.”
Indeed, most of the data on the three new drugs comes from one-year clinical trials. It is less clear how long that weight loss will continue.
Selling the drugs could be a problem, as well. Insurers often do not pay for obesity drugs, citing their questionable usefulness. And many doctors do not prescribe drugs for obesity out of concern about safety or a belief that diet and exercise are the best solutions.
But other doctors, and many patients, say that diet and exercise are often not enough. Meg Evans of Spring Valley, Calif., said she jumped at the chance to take part in a clinical trial of VivusÂ’s drug, Qnexa. Her knees hurt so much from the excess weight that she no longer dived for balls when playing goalie on her soccer team.
“At that point I had given up on everything else,” said Ms. Evans, 60, who had tried fen-phen, as well as an over-the-counter appetite suppressant and the Jenny Craig weight-loss program.
Ms. Evans does not know whether she received Qnexa or a placebo. But she lost 55 pounds in a year, dropping from 230 pounds to 175 pounds on her 5-foot, 9-inch frame. Now, she says, in soccer games she dives “like a 10-year-old.”
To persuade doctors and insurers to use their drugs, the companies plan to emphasize that their products are not for cosmetic purposes.
Rather, they mean to stress the medical benefits of controlling a root cause of diabetes, high blood pressure, cardiovascular disease and other conditions.
“There is no more cost-effective story in the pharmaceutical industry than obesity,” said Leland F. Wilson, the chief executive of Vivus, which is based in Mountain View, Calif. Orexigen and Arena are based in San Diego.
In Vivus’s clinical trials, those who received a high dose of Qnexa had statistically significant improvements in cholesterol, blood pressure and blood sugar, compared with those given a placebo.
“I was able to take some of my patients off several of their medications, especially their high blood pressure medicines,” said Dr. Michelle Look, a family practice physician in San Diego who was an investigator on the trial and is an adviser to Vivus.
Still, measures like cholesterol and blood pressure are only risk factors. No study has yet shown that weight-loss drugs actually prolong lives or reduce the incidence of heart attacks or strokes.
While the three drugs are closest to market, about three dozen other drugs are in development. Some experts say they have been impressed by the weight loss achieved in midstage trials by a combination of two hormones being developed by Amylin Pharmaceuticals, another California biotechnology company.
“We have so few treatments available to help individuals manage their weight,” said Dr. Robert F. Kushner, clinical director of the obesity center at Northwestern University, “that anything added to the toolbox is going to be helpful.”
Click to read the original article from The New York Times