CoStar Stent Fails Head-to-Head Test against Taxus

Early this month, Conor Medsystems LLC (Menlo Park, CA), a wholly owned subsidiary of Johnson & Johnson Inc. (J&J; New Brunswick, NJ), reported that its CoStar cobalt chromium stent failed to meet the primary endpoint of the recently conducted CoStar II clinical trial.

The study was designed to demonstrate the device's noninferiority to the Taxus stent, manufactured by Boston Scientific Corp. (Natick, MA). The primary endpoint was the incidence of major adverse cardiac events that occurred during the study, as measured by the incidence of target vessel revascularization, myocardial infarction (heart attack), stent thrombosis, and death. The major adverse cardiac event rate for the CoStar stent was 11%, compared with 6.9% for Taxus—a statistically significant difference.

Further analysis of the trial revealed that although the rates of heart attack and death were about the same for both devices, the patient group implanted with the CoStar stent required a significantly greater number of repeat revascularizations than did those who received the Taxus stent. The findings, initially slated to be reported late this month at the EuroPCR 2007 conference in Barcelona, Spain, were instead released by Conor several weeks earlier.

In making the announcement, Conor indicated that it would discontinue current clinical trials with CoStar, not complete its premarket approval application to FDA, and immediately begin withdrawing the CoStar stent from markets where it is already approved for distribution. These markets include countries in Europe, Asia, and Latin America. The company also said it would work with its commercial partners to secure and recall any product inventory in customer accounts.

In attempting to explain the failure of the CoStar drug-eluting stent in its head-to-head test with Taxus, J&J cited both the choice of drug and the dosage amounts as key factors. CoStar uses the drug paclitaxel, as does Taxus. J&J's Cypher drug-eluting stent, manufactured by its Cordis division, uses sirolimus. Taxus and Cypher are currently the only FDA-approved coronary stents.

The failure of CoStar was seen by most industry analysts as a major blow to J&J's stent business, with many calling into question the company's judgment in the $1.4 billion purchase of Conor Medsystems last February. Yet, at the time of the acquisition, many of those same analysts hailed the design of CoStar, which was typically described as novel or unique—and the first example of next-generation stents.

The CoStar stent uses tiny reservoirs lined with a bioabsorbable polymer to hold the drug. This design contrasts with the designs of both the Taxus and Cypher stents, in which the drug coating is affixed to a polymer coating on the stent structure. The absence of a surface polymer makes CoStar easier to implant, while at the same time significantly reducing patient exposure to the polymer substance. The polymer's potential for causing adverse effects remains unknown, but is still of concern to physicians.

In light of the results of the CoStar II trial, the alleged benefits of the CoStar platform are now being questioned by cardiologists, who are concerned that the stent's fundamental design may not allow for sufficient drug elution to prevent restenosis or reclogging. CoStar patients in the recent study experienced significantly greater incidence of scar tissue in and around the stent, resulting in a narrowing of the repaired artery.

Commenting on the results of CoStar II, Campbell Rogers, MD, chief technology officer of J&J's Cordis division, said, “While disappointed with the results, we remain optimistic about the ability of the novel Conor Medsystems reservoir platform to provide precise and controlled delivery of a therapeutic agent based on earlier proof-of-concept testing and trials. Unfortunately, the dose of paclitaxel used in this trial was ineffective.”

Rogers said that J&J will continue development work with CoStar, but that future designs would abandon paclitaxel in favor of sirolimus. He said that sirolimus “has been shown to be a versatile and potent antirestenosis agent with a wide therapeutic dosing range.”

Rick Anderson, J&J group chairman and worldwide cardiovascular franchise leader, confirmed the company's commitment to the CoStar design. “We are enthusiastic about the development of this platform with a versatile, highly effective drug like sirolimus,” he said. “Going forward, our clinical program will be heavily focused on the study of sirolimus on the platform, as well as on investigating the vast library of therapeutic agents accessible to our scientists through the research and development programs of pharmaceutical companies in the Johnson & Johnson family of companies.”

J&J reports that it had always intended to adopt sirolimus as the drug of choice on the CoStar platform.

Rogers said that Cordis expects to conduct the first clinical trials of CoStar with sirolimus early next year. Assuming all goes according to plan, industry analysts believe that the device is not likely to gain U.S. market entry until 2008 at the earliest. And with FDA under increasing pressure to strengthen its requirements for clinical data on coronary stents, the sirolimus-based CoStar stent could be delayed well beyond that.

J&J's share of the drug-eluting stent market, currently at about 45%, is expected to drop precipitously as new competitors enter the market. The Xience stent from Abbott (Abbott Park, IL) and the Endeavor stent from Medtronic Inc. (Minneapolis) are expected to enter the market in 2008.

Beyond new competition, some analysts say that J&J's weakened product development pipeline is of even greater concern. The company had been counting on CoStar to boost its market share.

“We're going to do everything we can to defend our position, but with four or five competitors in the marketplace, it's going to be a much more challenging environment for us,” said Nicholas Valeriani, J&J's worldwide chairman for medical devices.

According to some industry analysts, J&J—the company that introduced the first drug-eluting coronary stent to the market—may see its reputation degrade to that of a supplier of outdated stent technology.

Toward the end of this month, J&J's Cordis division announced an agreement to become the exclusive global distributor of a family of bare-metal stents manufactured by Medinol Ltd. (Tel Aviv, Israel). Cordis is not expected to apply for approval to market the devices in the United States until the first half of 2008.

Medinol has had a long and troubled relationship with Boston Scientific, J&J's chief rival in the stent market. In 2005, Boston Scientific agreed to pay Medinol $750 million to settle claims that the company violated its contract with Medinol and secretly employed the company's stent development technology in its own products.

Although suffering a number of setbacks over the last year, the global market for coronary stents is currently valued at around $6 billion.

© 2007 Canon Communications LLC

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