FDA advisers recommended that the Endeavor drug-coated stent be approved for sale. Now, doctors must be won over.
Medical advisers to the Food and Drug Administration recommended Wednesday that the agency allow Medtronic Inc. to sell its Endeavor drug-coated stent in the United States, setting the stage for a battle next year over a new generation of cardiac devices.
The nine-member panel voted unanimously that the device should be approved, but set two conditions reflecting recent safety concerns: Medtronic must conduct a safety study of the device for five years after it reaches the market and must address concerns about blood clots by including wording on the label recommending the use of anti-clotting drugs.
Medtronic's is the first of the so-called new generation of drug-coated stents to be recommended for approval for sale in this country. It is racing against rival product Xience from Abbott Laboratories to reach the coveted U.S. market.
Scott Ward, president of Medtronic's cardiovascular division, said he expected Endeavor to gain final approval from the FDA by the end of the year. The agency typically follows the recommendations of its advisory panels.
Medtronic already sells the Endeavor in Asia and Europe, and the Fridley-based device maker over the past year has beefed up its production capabilities, as well as its U.S. sales force. The company expects to have 100,000 stents on the market within a month of launch, Ward said.
The Xience stent is set to be reviewed in late November by the same panel of independent physicians. In addition, Boston Scientific Corp. is expected to launch its Taxus Liberte next year, making 2008 a year of heated competition in the stent market.
A $2 billion market
Right now, the drug-coated stent market is shared between Boston Scientific's Taxus and Johnson & Johnson's Cypher, collectively expected to bring in $2 billion in U.S. sales this year.
"Now you're going to see some significant disruption in that marketplace," said Tim Nelson, an analyst with Piper Jaffray & Co. in Minneapolis. "This is a big niche for Medtronic to exploit."
Stents are tiny wire-mesh tubes that are used to prop open arteries after doctors have cleared fatty deposits. Newer versions are coated with drugs to prevent restenosis, or a re-narrowing of the arteries. But recent concerns that the drug-coated stents may cause blood clots have hurt sales and raised the regulatory bar for new versions to be approved.
"This device has a real place in the DES [drug-eluting stent] universe," said Dr. Judah Weinberger, director of interventional cardiology at Columbia University and a member of the FDA advisory panel.
"It is clearly better than the bare-metal stent. Whether it's better than the other DES's, we'll find out."
Wednesday's meeting in Gaithersburg, Md., marked a key milestone in Medtronic's stent ambitions.
A particularly pointed question came early in the day: "What would cause somebody to walk into a cath[eterization] lab and use this device, instead of a Taxus or a Cypher?" asked Dr. Michael Domanski of the National Heart, Lung and Blood Institute of the National Institutes of Health. He is not a voting member of the panel.
Medtronic's principal investigator, Dr. Martin Leon, said that Endeavor was easier to insert, safer than its rivals and as effective in preventing restenosis.
In the past year, concerns that the drug-coated stents may raise the risk of blood clots have prompted some doctors to switch back to bare-metal versions. Doctors are still divided concerning the issue, and the uncertainty was reflected in Wednesday's deliberations.
FDA review officials summed up the results of three randomized clinical trials sponsored by Medtronic, involving a combined 2,100 patients. They concluded that the Endeavor stent is safer and more effective than bare-metal stents and comparable to Boston Scientific's Taxus.
Agency officials also noted that there was slightly more renarrowing of arteries with Endeavor vs. Cypher and Taxus. They said that safety concerns about blood clots disappeared after a year for the Endeavor vs. bare-metal stents.
Weinberger, who ended up voting for FDA approval, initially was skeptical.
"Lack of evidence is not evidence of lack," he said. "If I had my druthers, we'd be sitting here evaluating the data 12 to 18 months down the line."
He also noted that, while slight renarrowing of arteries didn't lead to more cardiac deaths or heart attacks during the trial, those patients had been overseen by highly trained doctors. It's not clear if the results might differ "in the hands of an average interventionist," he said.
Others pointed out that, even if the data didn't answer all questions, it was still a lot more information than regulators were able to review before previous recommendations concerning stents.
"I'm incredibly impressed" by the number of patients followed over three years, said Dr. David Naftel, professor of surgery at the University of Alabama in Birmingham. "If you're looking at data in four years," he said, "we got nothing."
As a condition for approval, the panel said that Medtronic should study at least 5,000 patients over five years after the device is on the market to track blood clots, heart attacks and cardiac deaths. It also added a second condition: Medtronic must recommend on its label the use of Dual Anti-Platelet Therapy -- a combination of aspirin and a second anti-clotting drug such as Plavix -- according to medical guidelines, which are currently 12 months.
Medtronic shares were up 88 cents, to $57.73, in late trading Wednesday.
After attending the meeting, a Boston Scientific official emphasized the lack of long-term safety data for Endeavor.
"Many physicians may want to wait for more data and patients may want to, too," said Jeff Mirviss, vice president for marketing for Boston Scientific. He said that his company is presenting five-year data concerning Taxus at a cardiology conference in Washington that starts Oct. 20.
Chen May Yee 612-673-7434