Drugmakers chase elusive goal: an effective diet pill

┬áDespite 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.

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.

A recent study conducted partly by the United States 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 foiled 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’ 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.

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 3 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 But the next year, two of the drugs used in the combination were withdrawn from the American market because they caused damage to heart valves, leaving the drugmaker Wyeth with about $21 billion in liability.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 but 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.

 The new drug candidates work through the central nervous system to influence appetite, and the United States Food and Drug Administration 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 success, failed to win FDA 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.

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.

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 because they believe 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, California, said she jumped at the chance to take part in a clinical trial of Vivus’ drug, Qnexa.”At that point I had given up on everything else,” said Evans, 60, who had tried fen-phen, as well as an over-the-counter appetite suppressant and the Jenny Craig weight-loss program.

Evans does not know whether she received Qnexa or a placebo. But she lost 25 kilograms in a year, dropping from 105 kilograms pounds to 80 kilograms on her 175-centimeter 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, California. Orexigen and Arena are based in San Diego.

In Vivus’ 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.

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 mid-stage 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.”