News Update

LOS OSOS, Calif. — Next week, advisers to the Food and Drug Administration will recommend whether the agency should approve the first new prescription diet pill in 13 years.

The F.D.A. rejected the drug under review, Qnexa, in 2010, amid safety concerns, and the drug’s manufacturer is now presenting additional data to argue its case. 

But thousands of people here in central California, where Qnexa’s inventor ran a weight-loss clinic, and others across the country have not had to wait for the drug’s approval. Through a regulatory loophole of sorts, many obesity doctors prescribe two separate drugs that, when taken together, are essentially the same medicine.

The widespread use of the unsanctioned combination reflects the often desperate desire for a medicine to help overcome the nation’s epidemic of obesity, doctors and patients say. 

The experience in this idyllic coastal community about midway between San Francisco and Los Angeles also provides a look at what might happen if Qnexa were approved. Use of the close substitute grew as word spread that some patients had experienced substantial weight loss. Some people here regained weight after stopping the treatment, and some experienced unpleasant side effects such as memory loss.

“I can’t tell you how many people I sent to him because they saw the success I had,” said Lynn Adams, a retired teacher, referring to Dr. Thomas Najarian, the inventor of Qnexa who opened a weight-loss clinic here in 2001.

Ms. Adams said she took the two drugs for a year and lost about 80 pounds. She has taken the drugs from time to time since then but is off them now and has gained about half the weight back.

Qnexa, developed by the company Vivus, is a combination of two already approved drugs — a stimulant called phentermine and an anticonvulsant calledtopiramate — that seem to work together to quell appetite. Even though the F.D.A. declined to approve Qnexa two years ago, citing the risks of birth defects and cardiovascular problems, doctors are allowed to prescribe the components off-label as they see fit.

Many do. Dr. Christopher D. Still, director of the obesity institute at Geisinger Health System in Danville, Pa., estimated that 70 percent of obesity specialists prescribed the combination. “There is a subgroup of individuals that really feel satiated” when treated with the two drugs, said Dr. Still.

Only one drug, Roche’s Xenical, is currently approved for long-term use in treating obesity, and it is unpopular because of embarrassing digestive side effects. The F.D.A. rejected three obesity drugs, including Qnexa, in 2010 and 2011, citing different safety concerns for each.

On Friday, the F.D.A.’s staff released its analysis of the new Qnexa data and said it was still concerned about potential heart problems and birth defects in women who become pregnant while taking the drug. On Wednesday, an advisory panel will review the drug and make its recommendation. The staff will ask the committee to consider whether Vivus should do a large clinical trial to judge cardiovascular risks before the drug can be approved. The F.D.A. will have until April 17 to make a decision about it.

Dr. Najarian, who sold his clinic in 2010, said Vivus would not allow him to talk about his experience treating patients with phentermine and topiramate. While doctors can prescribe drugs off-label, drug companies cannot promote such use. Dr. Najarian has been a part-time employee of Vivus since 2006.Timothy E. Morris, the chief financial officer of Vivus, said Dr. Najarian’s practice did not constitute off-label promotion because Qnexa was “a separate product,” often with different doses, from the two components.

The weight-loss clinic, called Najarian Center, “certainly treated thousands of patients,” said Carol Rowsemitt, a nurse practitioner who worked at the clinic. Besides the drugs, the regimen involved modest exercise, a low-calorie diet and nutritional supplements, some sold by the clinic.

Ms. Rowsemitt said patients had been informed that the drugs were being used off-label and that Dr. Najarian had a financial stake in the combination.

She said side effects were carefully monitored, and she knew of no birth defects. She said, however, that some other doctors in the region had also started using the phentermine-topiramate combination “without being educated on how to use it.”

Phentermine, a stimulant, is approved for short-term use for weight loss. Part of the once popular fen-phen diet pill combination, it remained on the market after two other drugs were withdrawn in 1997 for damaging heart valves.

Topiramate, or Topamax, is approved for epilepsy and migraines, although half of the obesity specialists in one academic survey said they had prescribed it for weight loss. Critics say that using drugs for weight loss does little to change the underlying behavior leading to obesity.

“Everyone wants a quick fix,” said Dr. Sidney M. Wolfe, director of health research at Public Citizen. “But it’s also dangerous.”

Melané Lange of Los Osos once thought that way as well. When she worked for Weight Watchers here, she recommended diet and exercise and used those methods herself.

But it was hard work. So last October, she had her doctor prescribe the two drugs and lost more than 10 pounds in time for a vacation. “Taking a pill in the morning, taking a pill at night, that’s not a lot of work,” Ms. Lang said. “I was losing patience this time. I didn’t want it to take six months.”

Dr. Philip A. Borgardt, who bought Dr. Najarian’s practice and moved it to nearby San Luis Obispo, Calif., said weight loss was not simply a matter of willpower.

“If it was that easy, they wouldn’t have come to see us,” he said. “The biggest barrier we have to treating obesity is we blame the patient.”

The practice says on its Web site that it provides “healthy and rapid weight loss!” Until about two weeks ago, the site said that the treatment resulted in “greater than 10 percent weight loss in clinical trials,” an apparent reference to the Qnexa results. But Vivus was concerned the information would look like off-label promotion, so the clinic posted its internal data instead, Dr. Borgardt said. The practice is also changing its name from the Najarian Center to TNC Weight Loss to distance itself from Vivus, he said.

Not everyone had success with the regimen. Kat Lauterback, a county worker, said the topiramate caused memory lapses, a well-known side effect.

She said she put up with it for a few months while losing 20 or 30 pounds. But when the weight loss slowed, tensions developed between her and Dr. Najarian. “I found the weight came back very quickly once I went off the drugs,” Ms. Lauterback said.

Roughly two-thirds of American adults are obese or overweight, so a safe pill that assists in weight loss would be lucrative for any company making it.

Wall Street analysts estimate that sales of Qnexa could reach at least several hundred million dollars a year. Although competitors could not copy the patented formulation, doctors could continue to prescribe the two component drugs, which are both available in cheap generic forms.

In addition to Vivus, the makers of the two other drugs rejected by the F.D.A. in recent years are marshaling new data to try again to persuade the agency that the health benefits from the weight loss provided by the drugs trump the side effects.

Of the three drugs, Qnexa provided the biggest weight loss, according to clinical data. Patients taking the highest dose lost an average of 10.6 percent of their body weight after a year, compared with 1.7 percent for those getting a placebo.

Dr. Najarian, a Harvard-trained physician, worked in the late 1990s at Interneuron Pharmaceuticals, near Boston, that had developed Redux, one of the fen-phen drugs withdrawn from the market.

He chanced upon a study showing that Topamax caused people to lose weight and thought that it might be a good new partner for phentermine, with the stimulant offsetting Topamax’s brain-numbing effects. Neither Interneuron nor Johnson & Johnson, the manufacturer of Topamax, wanted to pursue it, he said in a conversation at his home here overlooking Morro Bay. So he patented the combination and licensed it to Vivus.

As of Sept. 30, Vivus had paid Dr. Najarian $220,000 and given him options to buy 40,000 shares of stock, according to a company filing. Those shares would be worth nearly $500,000 at current prices. If Qnexa is approved, Vivus will pay him $1 million, provide options for 20,000 shares, and pay royalties.

“I don’t care about that stuff,” said Dr. Najarian, 64. “I’d just be happy if the drug gets on the market.”

By ANDREW POLLACK

Published: February 16, 2012

A version of this article appeared in print on February 17, 2012, on page B1 of the New York Times with the headline: U.S. to Review Diet Treatment Once Rejected.

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