FDA Panel Provides Cautious Support for Drug-Eluting Stents

When FDA's circulatory system devices advisory panel met earlier this month to review drug-eluting coronary stents, many industry analysts raised concern that use of the devices could be sharply curtailed given the firestorm of safety issues that had been raised prior to the meeting. Yet, after two days of data review and analysis, the panel adopted a more moderate stance than generally anticipated. Although acknowledging that previous clinical studies of drug-eluting stents indicated a greater incidence of late-term thrombosis than with bare-metal stents, the panel concluded that the magnitude of the greater incidence is uncertain and additional data are needed. Despite the apparent increase in stent thrombosis, drug-eluting stents were not found to increase the risk of death or myocardial infarction compared to bare-metal stents.

The panel also emphasized that drug-eluting stents are generally safe and effective when used as intended. There seemed to be a general consensus that many of the reported problems may be associated with off-label use on patients with multiple blockages or complicating medical conditions such as diabetes. FDA medical officer Robert Fiorentino, MD, told the panel, “The majority of drug-eluting stents are implanted in patients or in vessels with characteristics different than those studied to support marketing approval.”

The consensus of the panel was that safety concerns do not outweigh the benefits of drug-eluting stents, which have demonstrated superiority over the bare-metal variety in reducing the risk of restenosis, the build-up of scar tissue at the site of the artery repair. Restenosis frequently requires repeat angioplastic revascularization and restenting to restore adequate blood flow.

At the meeting, the panel also paid a great deal of attention to the issue of antiplatelet therapy following stent implantation. When drug-eluting stents were first introduced, cardiologists typically recommended a six-month regimen of a blood-thinning drug such as clopidogrel in combination with low-dose aspirin. According to the panel, “ The optimal duration of dual antiplatelet therapy, particularly in more-complex patient and lesion subsets, is unknown, as is whether or not an extended course of dual antiplatelet therapy will prevent late thrombosis.” While the panel did not officially recommend a longer period of usage, many physicians have speculated that patients with drug-eluting stents might have to continue taking medication for a longer period of time—perhaps indefinitely.

Although the panel called for more-detailed postmarket studies on the safety and efficacy of drug-eluting stents, FDA is not expected to implement any changes in the premarket approval process. Thomas Gunderson, managing director and senior medtech research analyst with Piper Jaffray & Co. (Minneapolis), said, “FDA is not likely to now raise the bar for newcomers to the market. The panel is apparently not recommending any changes in procedures or requirements in clinical studies as part of the FDA approval process. The emphasis here is on postmarket surveillance and follow-up.” Gunderson believes that the panel's preliminary findings are generally favorable to both manufacturers with devices already on the market as well as those that hope to gain entry in the future.

The panel's final report and recommendations are not yet available, but coronary stent manufacturers were buoyed by the preliminary findings coming out of the meeting and immediately initiated marketing and public relations programs to regain the confidence of both physicians and patients. Boston Scientific Corp (Natick, MA), manufacturer of the Taxus drug-eluting stent, ran full-page ads in several newspapers emphasizing the safety of its device. The company's Web site led with the banner headline “Get the Facts about Drug Eluting Stents.” Cordis Corp (Miami Lakes, FL), the cardiovascular division of Johnson & Johnson Inc., sent doctors a detailed letter about the safety and benefits of its Cypher drug-eluting stent. Both companies hosted conference calls with industry analysts to discuss the preliminary findings of the FDA panel.

Boston Scientific and Cordis both presented clinical data to the FDA panel, as did Medtronic Inc. (Minneapolis) and Abbott Labs (Abbott Park, IL). Medtronic says it is on target to gain approval for its Endeavor drug-eluting stent in the latter half of 2007. Abbott's Xience drug-eluting stent is currently undergoing clinical trials in the United States. The device received the CE mark for European distribution earlier this year. Conor MedSystems Inc. (Menlo Park, CA), manufacturer of the CoStar drug-eluting stent, which is also poised for near-term entry into the U.S. market, did not participate in the FDA panel meeting. Last month, Cordis announced that it plans to acquire Conor for $1.4 billion.

While industry analysts debate the impact of safety issues on the near- and long-term direction and growth potential of the drug-eluting coronary stent market—currently valued at about $6 billion worldwide—manufacturers now face the additional threat of product-liability lawsuits. Although federal law has generally protected manufacturers of medical devices that have gone through FDA's rigorous premarket approval process, that protection is currently being challenged in the courts.

© 2006 Canon Communications LLC

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