Earlier this month, FDA’s circulatory systems devices panel unanimously recommended full agency approval of the Endeavor drug-eluting coronary stent, manufactured by Medtronic Inc. ( Minneapolis). The panel’s recommendation was predicated on two conditions: a five-year follow-up study including 5000 or more patients, and labeling to emphasize the benefit of dual antiplatelet drug therapy for at least one year following stent implantation.
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The Endeavor stent system comprises four components: a cobalt alloy based stent, the polymer phosphorylcholine, the drug Zotarolimus, and the stent delivery system. FDA’s nine-member panel reviewed extensive data comparing Endeavor to Medtronic’s bare-metal Driver stent and the only drug-eluting coronary stents currently available in the United States: Cypher, manufactured by Cordis Corp. ( Miami Lakes, FL), a Johnson & Johnson company, and Taxus, manufactured by Boston Scientific Corp. ( Natick, MA).
According to data presented at the panel meeting, Endeavor generally performed well on all indices of clinical efficacy and safety. However, some recent data undermined Medtronic’s highly touted claim of the stent’s superior safety record when compared with Taxus and Cypher. Results from Medtronic’s most recent clinical study indicated that Endeavor patients experienced a slightly higher rate of blood clots than those implanted with the Taxus stent. While the reported clots were not late term and did not result in heart attacks, the findings still raised concern among some industry analysts. Nevertheless, few observers expected that the findings would jeopardize the panel’s widely anticipated recommendation for approval.
Medtronic is currently conducting a long-term clinical study involving 8800 patients, which will compare Endeavor with the Cypher stent. The endpoint of the Patient Related Outcomes with Endeavor versus Cypher Stenting Trial (PROTECT), which enrolled its first patients last May, will be the overall incidence of stent thrombosis at three years after implantation.
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Medtronic’s Ward: Next-gen benefits.
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Scott Ward, president of Medtronic’s cardiovascular business unit, expressed the company’s pleasure with the panel’s recommendation. “We are very pleased with the outcome of today’s panel meeting and appreciate the advisory committee’s careful consideration of the extensive data on the Endeavor stent,” he said. “We will continue to work with FDA to bring the Endeavor stent to the U.S. market as soon as possible so that patients and physicians in the U.S. can benefit from this next-generation technology.”
Since FDA often follows the recommendations of its panels, Endeavor is widely expected to be the first drug-eluting stent to be authorized for U.S. market entry since Taxus was approved in March 2004. Endeavor received the CE mark in 2005 and is currently available in more than 100 countries around the world.
When Endeavor finally receives FDA approval, it will face a much more daunting market than did its predecessors. Less than a year after Cypher and Taxus were both available in the United States, drug-eluting stents nearly displaced their bare-metal predecessors, capturing 85–90% of the market for coronary stents. As the devices continued to gain the support of interventional cardiologists, the market grew at a torrid pace, reaching a worldwide valuation of around $6 billion by the end of 2005.
In March 2006, however, the widely reported Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study, presented at the annual meeting of the American College of Cardiology, suggested that angioplasty with stent implantation yielded essentially the same outcomes as drug therapy accompanied by lifestyle changes (e.g., diet and exercise).
Later that year, the market took a more serious blow, as a number of clinical studies raised concerns about potentially deadly blood clots associated with the use of drug-eluting stents. Both stent manufacturers and FDA suggested that improper and off-label use of the devices contributed to the adverse findings. But the resulting attention in the industry, business, and general-interest press resulted in a dramatic cooling of the market. In December 2006, FDA met with manufacturers to address safety issues associated with drug-eluting stents.
Dropping from their previous lofty utilization rates of 85–90%, drug-eluting stents presently account for around 65% of stent implantations in the United States. Overseas markets have declined as well, with the United Kingdom’s National Health Service, the world’s largest publicly run healthcare agency, considering whether or not to ban their use entirely and go back to bare-metal devices.
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Stanford Group’s Wald: A cautious approach.
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More long-term clinical data about the use of drug-eluting stents are expected to dispel many of the safety concerns that have arisen over the past two years. Even so, most analysts anticipate a slow recovery for the market, particularly as next-generation devices are introduced. “We will likely never get back to those usage rates—or if we do, it will take a long, long time,” says Jan Wald, managing director and medical technology analyst with the Stanford Group Co. (Houston). “New patterns of physician and patient behavior and belief systems are already taking hold, resulting in an extremely cautious approach to drug-eluting stents. Overall, at this juncture, an eventual penetration rate of 75% may be the most optimistic forecast.”
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PJC’s Nelson: No further erosion.
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Tim Nelson, assistant vice president and medtech analyst with Piper Jaffray & Co. ( Minneapolis) largely concurs. “The current drug-eluting stent utilization rate of 65% appears to be the floor. We’ve been there now for several quarters and, barring any catastrophic developments, there does not appear to be any indication of further market erosion. It may get back to the mid-70% range, but going forward, that will largely depend upon the comfort level and confidence that physicians and patients have in the devices.”
Medtronic is hoping for full FDA approval of the Endeavor stent before the end of the year. That’s not entirely unrealistic, says Wald, “but the first quarter of 2008 is a more likely scenario.” Many industry analysts believe that Endeavor could capture 15% of the market, or more, soon after product launch.
Meanwhile, Abbott Labs ( Abbott Park, IL) will present its Xience stent to the FDA circulatory systems devices panel next month. Most industry analysts believe that stent will join Cypher, Taxus, and Endeavor in the U.S. market by the second quarter of 2008.
As the situation stabilizes and competition heats up, however, the contenders will likely be jockeying for position in a market that is considerably smaller than was envisioned even as recently as 18 months ago.
As if that cautionary outlook weren’t enough, Medtronic received a reminder that the market for heart rhythm devices has also suffered from recent safety concerns. Just a few days after FDA’s panel recommended approval of the Endeavor stent, Medtronic reported that it was voluntarily recalling its line of Sprint Fidelis lead wires, which are used in several of the company’s implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators. Approximately 268,000 of the leads have been implanted worldwide.
The Sprint Fidelis leads are subject to fractures that could cause inappropriate shocks, resulting in either excessive or deficient amounts of therapy. According to Medtronic, the leads should no longer be implanted, and any inventoried products should be returned to the company. Patients implanted with the leads or those uncertain as to whether or not their model is affected were advised to contact their physicians. According to the company, fractures in Sprint Fidelis lead wires may have contributed to five deaths.
© 2007 Canon Communications LLC
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