FDA Declines To Approve Orexigen Diet Drug

WASHINGTON (AP) - The government on Tuesday unexpectedly rejected what appeared to be the most promising candidate among a class of new diet drugs, wiping out hopes for a new medication to fight obesity anytime soon.

Orexigen Therapeutics Inc. said the Food and Drug Administration is concerned about the heart side effects of its drug Contrave and will require a new study, a costly undertaking that may prove too burdensome for the small drugmaker.

The FDA's ruling marks the third rejection of a weight loss drug in recent months, raising questions about whether any new drugs in the class can be made safe enough to win approval. The FDA has not approved a new diet pill in more than a decade.

The FDA request for an additional study suggests the agency may yet approve the drug, but makes that path much more difficult. The news led to a sell-off that wiped out nearly three-quarters of the market value of the company.

Orexigen said it is disappointed with the FDA's decision and will work with the agency to determine its next step.

"We are surprised and extremely disappointed with the agency's request in light of the extensive discussion and resulting vote on this topic at the Dec. 7 advisory committee meeting," said President and CEO Michael Narachi, in a conference call with investors.

Narachi acknowledged that studies of the kind requested by the FDA are normally "fairly large," and would require the company to raise additional money. Clinical trials to study rare events like heart attack can take years to conduct and cost millions of dollars.

Analysts had viewed Contrave as the most promising of three new diet pills recently submitted to the agency. Contrave is a combination pill, mixing an antidepressant with an anti-addiction drug to curb appetite. Four out of 10 patients taking Contrave for a year lost at least 5 percent of their body weight. Those results narrowly met FDA's guidelines for effectiveness.

Given the drug's limited benefit, FDA's rejection was not surprising, according to drug industry analyst Erik Gordon.

"You have life-threatening possible side effects in return for modest weight loss that might not be produced in the real world - no wonder the FDA wants more data," said Gordon, a professor and analyst at University of Michigan's Ross School of Business.

La Jolla, Calif.-based Orexigen does not currently have any products on the market, making Contrave a key to the company's growth and survival. In trading Tuesday, Orexigen shares tumbled $6.59, or 73 percent, to $2.50.

Analysts expect any obesity drug reaching the market to have the potential to become a billion-dollar seller.

With the U.S. obesity rate for adults nearing 35 percent, the FDA has acknowledged the need for new weight loss drugs. But the agency rejected two other drugs last year due to safety risks, a long-standing issue that has plagued weight loss treatments for decades. Those drugs were made by fellow California drug developers Vivus Inc. and Arena Pharmaceuticals Inc. Both companies have said they plan to resubmit their drugs for approval.

Contrave has been pegged as a more promising treatment because of its relative safety. Unlike the other two drugs reviewed last year, it received a positive vote from the FDA's panel of outside advisers, who voted 13-7 that the drug's modest weight loss benefits outweighed its risks.

But the FDA meeting assessing the drug was not free of criticism. FDA scientists and safety advocates complained that the company enrolled few elderly patients or patients with a history of heart disease in its trials, making it difficult to determine the drug's safety in patients who are likely to need it most.

Heart side effects have been an issue with diet drugs, most notably with Wyeth's diet drug combination fen-phen, which was pulled off the market in 1997. In October, Abbott Laboratories withdrew its drug Meridia after evidence it increased the risk of heart attack and stroke.

Currently there is just one prescription drug on the market for long-term weight loss: Roche's Xenical, which is not widely used. Several other generic drugs are approved for short-term weight loss, including phentermine.