Dash For Diet Drug

Dash For Diet Drug [The San Diego Union-Tribune]

From San Diego Union-Tribune (CA) (January 31, 2010)

Jan. 31--For decades, the pharmaceutical industry has chased an elusive target, a drug that will make you lose weight without putting your health at risk.

For a brief period in the 1990s, the two-drug combo known as Fen-phen achieved blockbuster status -- before potentially fatal side effects knocked it off the market. More recently, the risk-benefit profile of the leading diet drug Meridia has come under scrutiny, with European authorities deciding to ban it this month.

Now, three California biotechnology companies are trying to convince the U.S. Food and Drug Administration that they’ve found drugs that are effective and safe. Not only that, they say the drugs can help with conditions that often accompany obesity, such as high cholesterol or blood pressure.

If the companies are right, it could bring about a sweeping change in the treatment of obesity while also bringing in blockbuster profits for the companies -- San Diego’s Arena Pharmaceuticals and Orexigen Therapeutics, along with Vivus in the San Francisco Bay Area.

"The stage is set for obesity, to finally make some paradigm changes in the way the condition is thought about and treated," said Michael Narachi, chief executive of Orexigen.

Narachi pointed to new drugs that have dramatically improved the treatment of conditions like high cholesterol or hypertension while creating multibillion-dollar markets for drug companies. Obesity, he said, offers the same kind of potential for advance.

Nothing will alter the traditional prescription for weight loss -- diet and exercise. But the companies say their drugs could give physicians an additional tool to treat excess weight as a medical condition with potentially serious consequences.

All three announced study data last year that showed significant numbers of patients losing 5 percent or more of their weight. Arena and Vivus have since filed with the FDA for clearance to sell their drugs, while Orexigen says it will do so in the coming months.

Donna Ryan, a researcher who leads the Obesity Society in Maryland, said the data suggest all three are effective enough to win the FDA’s blessing when it rules late this year or in 2011. Ryan said safety, the other factor the agency looks at, is harder to judge.

While there are a few drugs doctors prescribe for weight loss, Ryan said it is important to have new options that might prove more effective.

"It’s a great thing," Ryan said of the potential for multiple drugs to win approval. "In terms of what tools physicians have to manage weight loss, we haven’t gotten any drugs out to help us in a decade."

Of the three drugs, the only truly new one comes from Arena. Its approach was to design a drug, known as lorcaserin, that would hit the same molecular "receptor" the fenfluramine component of Fen-phen targeted for weight loss, without hitting other receptors that caused side effects.

The other two companies have combination drugs. Orexigen’s Contrave combines the antidepressant Wellbutrin , known generically as bupropion, with a sustained-release version of naltrexone, which is used to treat alcoholism and other addictions.

Vivus’ Qnexa combines a generic form of the appetite suppressant phentermine, the other component of Fen-phen, with the anticonvulsant drug topiramate.

Other companies, including San Diego’s Amylin Pharmaceuticals, have weight-loss drugs in earlier stages of development. Orexigen also has a second drug in development.

With two-thirds of Americans qualifying as overweight, according to the Obesity Society, there appears to be room for multiple drugs in the market.

"There’s room for 13, or 30, new drugs," Arena chief executive Jack Lief said. "I’d like to see all three of them be approved, because I think that will open up the market very significantly. Patients will go to their physicians and want to do something about their weight."

Ted Tenthoff, a biotech analyst who follows Arena for investment bank Piper Jaffray & Co., said the drugs could end up addressing distinct segments of the market.

Tenthoff said Vivus’ Qnexa, which showed the most dramatic weight loss in trials, would likely would end up being prescribed for the heaviest patients -- though the company also has lower-dose formulations it says will address a broad range of patients.

Tenthoff said a better safety profile could provide a niche for Arena’s lorcaserin with less-obese patients, despite the drug’s weaker data on weight loss. The company believes this also could make it the drug doctors try first.

Orexigen, whose drug Tenthoff described as falling somewhere between the other two, plays up Contrave’s potential to help patients with other conditions that often accompany obesity. For example, Narachi said one-third of obesity patients also suffer from depression and therefore might want a weight-loss drug that includes an antidepressant.

Many patients also might try more than one approach.

"What typically happens in markets like this is that there’s quite a bit of churn," Narachi said. "There might be somebody who tries a product and decides to stop, either because it’s not effective for them or because some patients are more sensitive to certain tolerability aspects than others. Or people may lose a certain amount of weight on one product and then switch to another one and see if they can lose a little bit more."

As the FDA considers whether to approve the drugs, a big question is likely to be safety. Past problems with obesity drugs could be one reason investors have been slow to embrace the three companies’ stocks, all of which trade in single digits.

Inevitably, regulators will think back to the Fen-phen fiasco, which led drugmaker Wyeth to set aside $21 billion to resolve litigation related to Fen-phen’s links to heart damage and lung disease.

Tenthoff said more recent experience with Meridia could make the FDA that much more conservative. Data that linked that drug to strokes, heart attacks and other cardiovascular problems led European regulators to suspend sales of the drug this month while the FDA asked for a stronger warning label.

"These drugs are going to be used in millions of patients," Tenthoff said. "That is going to be on the mind of the FDA."

Questions about safety also could make some patients hesitant, even if the FDA approves all three drugs.

The companies point to substantial pent-up demand in the market, given the lack of new weight-loss drugs in recent years. When Fen-phen was on the market, prescriptions tripled in one year to hit 20.6 million in 1996.

Right now, a major activity for all three companies is seeking large pharmaceutical company partners with sales forces to help market the drugs if they get on the market. Narachi said multiple potential product launches around the same time also could help speed acceptance.

"There will be three companies, perhaps with three partners, all trying to convince people that pharmacotherapy approaches should be more heavily considered as a treatment for obesity," Narachi said.

The Obesity Society’s Ryan said doctors and patients are eager for new tools.

"They are clamoring for aids to help with their patients," Ryan said. "Just telling people to eat less and exercise more is not going to slow the obesity epidemic."

Thomas Kupper: (619) 293-1037; thom.kupper@uniontrib.com

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Posted: February 2010


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