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US panel backs anti-clot drug despite concerns

By REUTERS

* FDA advisers: J&J, Bayer drug benefit outweighs risk

* Advisory panel votes 15-2 in favor of Xarelto

* Panelists caution against long-term use

* FDA approval decision due May 28

* Some analysts see possible delay in FDA final decision

(Recasts first paragraph; adds comment, background)

By Susan Heavey

WASHINGTON (Reuters) - Johnson & Johnson and Bayer AG's anticoagulant drug Xarelto was backed by a U.S. advisory panel Thursday despite concerns over possible side effects and worries about long-term use.

J&J is seeking marketing approval for the once-a-day pill, developed by Bayer, to prevent dangerous blood clots for up to 14 days in patients following knee replacement surgery and up to 35 days for hip replacements.

The U.S. Food and Drug Administration panel of outside advisers voted 15 to 2 in favor of Xarelto, but cited lingering concerns about possible liver damage and bleeding.

Panel chairman Michael Lincoff, of the Cleveland Clinic Foundation, said Xarelto is "still favorable" but that "there's a bit of caution." The drug is already used in Europe and Canada.

The FDA will weigh the panel's recommendation before making its final decision on the drug, also known by its generic name rivaroxaban. A decision is expected May 28. The agency usually, but not always, follows the advice of its panels.

If approved, Xarelto would be the first oral blood thinner approved in the United States since the widely-used drug warfarin was approved more than 50 years ago. It would also compete with Sanofi-Aventis SA's injectable drug Lovenox, also known as enoxaparin.

While the market for knee and hip replacement patients is not huge, the company along with Bayer is studying possible other uses, such as stroke prevention, that would require patients to take the drug for longer periods of time.

LONG-TERM WORRIES

Some panelists were concerned doctors might go ahead and use Xarelto for longer than directed, or off-label uses, even though the drug's long-term effects are unclear.

"We should not rush into this. We should wait until we get more data," said Sidney Wolfe, the acting consumer representative on the panel and head of advocacy group Public Citizen's Health Research Group. He voted against the drug.

Some 800,000 patients in the United States undergo knee and hip replacements each year, the FDA and company said. Stroke strikes nearly as many Americans each year and the potential population for a stroke-prevention therapy could be much larger.

FDA staff scientists earlier raised a number of questions about the company's data, including the bleeding and liver risks as well as how J&J combined data from various studies.

"Any type of analysis with this kind of limitation can yield spurious results," FDA reviewer Qing Xu told the panel.

Panelist Sanjay Kaul, a Cedars-Sinai Health Institute cardiologist who voted against the drug, agreed the company's analysis was unconvincing. "I saw a risk-benefit (profile) that was a wash," he said.

J&J officials told the panel its studies showed Xarelto was more effective than enoxaparin, a benefit that far outweighed potential risks. It also said the drug was more convenient for patients because it was available as a single-dose daily pill and had fewer interactions with food and other medicines.

Warfarin, sold under the brandname Coumadin by Bristol-Myers Squibb Co, is also take orally but can be difficult for doctors to find the right dose for patients and requires frequent blood tests.

Peter DiBattiste, head of cardiovascular treatments at J&J, told the panel Xarelto was "well-tolerated with modest increases in bleeding."

Other company representatives also said Xarelto was unlikely to have caused liver-related deaths seen in some of the studies. Long-term studies are underway, the company said.

John Senior, associate director for science in the FDA's Office of Surveillance and Epidemiology, said early data from one trial, called Atlas, "looks good... but I want to see more" before concerns about liver problems are eased.

Some analysts said they expect the FDA to delay approval despite the panel's recommendation.

The agency may ask for the final results of the Atlas study to be submitted before it makes a final decision on the application, Credit Suisse analysts wrote in a research note. If that was the case, the drug would not be approved until early 2010, they said.

But more importantly, the analysts said, the FDA panel's support "was reassuring so the product's potential in the longer-term indications... remains robust." (Editing by Bernard Orr and Tim Dobbyn)

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