Boston Scientific (Natick, Massachusetts) in mid-July reported a substantially widened recall of its lucrative Taxus paclitaxel-eluting coronary stent. The latest recall expanded an earlier July recall involving about 200 Taxus Express2 Systems, due to characteristics in the delivery catheters that have the potential to impede balloon deflation during a coronary angioplasty. The company said during a conference call that the expanded recall would involve about 85,000 Taxus stent systems as well as about 11,000 Express2 stent systems. Overall, the company said it has shipped more than 500,000 Taxus stent systems and more than 600,000 Express2 stent systems.

The popular Taxus drug-coated stent and the company's older Express2 bare-metal stent were linked with three deaths and about 43 injuries. The company noted that the recalls do not affect the Express SD and LD biliary stent systems, and it stressed that the recalls do not affect patients who already have the devices implanted since the difficulty is with the delivery system and occurs at the time of insertion, not afterward.

Following the July 16 announcement of the broadened recall, the company held a web cast the following week, attempting to recover lost goodwill with physicians and saying it was working hard to restore their confidence. Paul LaViolette, senior vice president and group president of the company's cardiovascular business unit, acknowledged that while the Taxus and Express systems, combined, are used more than any other stent systems, that trend would not continue if physician confidence is undermined. "We have let you down," he said. "This no-deflate problem is real, we're acting aggressively, but we also know that by having had to take two steps to ... get there is not the way we would have liked it to go, and it has affected your confidence in whether or not we are in full control of our product." The company, he said, would continue to work "exceptionally hard" to regain that trust. "We will get there [and] we will get there in partnership with you."

LaViolette reported completion of the recall on July 19, saying that Boston Scientific had begun replenishing the affected supplies. And he reiterated the company's position that the problem was confined to the catheter delivery system, not with any failure of the stent itself. He said the defect occurred in less than one in 10,000 procedures, but that the company wasn't taking chances with the rest of the inventory. Thus, Boston Scientific had to draw very broad boundaries around its degree of certainty, he said. None of the recalled stent systems will be redistributed anywhere in the world, LaViolette said. He said also that all inventory in the U.S. should be replaced by early August. Additionally, the company disclosed, in a note sent to doctors, that besides problems with the Taxus stent, that there had been 52 complaints linked to the use of 600,000 Express2 stents. These included two deaths and 25 serious injuries.

While the company said the most recent recall should be sufficient, it may not be out of the woods entirely. The FDA reportedly is conducting a "top priority" review of the recall and has asked for more information about how the company determined which stents were safe. The review will include an inspection of Boston Scientific's stent manufacturing plants in Maple Grove, Minnesota, and Galway, Ireland.

In tandem with the recall announcements, doctors at the Cleveland Clinic (Cleveland, Ohio) said that they would "highly restrict" use of the Taxus stent only to procedures where the competing Cypher sirolimus-eluting stent from the Cordis (Miami Lakes, Florida) unit of Johnson & Johnson (J&J; New Brunswick, New Jersey) isn't a good option. These would include, for instance, patients with difficult-to-reach blockages, said Eric Topol, director of cardiology at the clinic. Other facilities, including Massachusetts General Hospital, Brigham & Women's Hospital and Beth Israel Deaconess Medical Center (all Boston, Massachusetts), also suspended their use of the stent until demonstration of clinical safety. Stanford Medical Center (Palo Alto, California), Duke University Medical Center (Durham, North Carolina) and the Emory Heart Center (Atlanta, Georgia) were among those that said they expected to significantly reduce their use of Taxus stents for now.

Larry Haimovitch, president of Haimovitch Medical Technology Consultants (Mill Valley, California) who covers the cardiovascular sector for Cardiovascular Device Update, said Boston Scientific is fortunate in some respects. "I think there's one thing that's very, very lucky for them – that there's only one other competitor [in this space]," he told CDU. "At least they have some good luck on their side here from the standpoint of timing. You've got one other competitor who may also be capacity-constrained."

Jim Tobin, president of Boston Scientific, estimated that the recall would set back Taxus inventory in the U.S. about a week, and about four to six weeks internationally. "The situation, while obviously something that we are not happy about, is not a complete catastrophe," he said.

Longer approval delays for Champion

Guidant (Indianapolis, Indiana) apparently will have to wait even longer than last reported for approval of its first drug-eluting stent (DES) in Europe and the U.S. In a conference call early last month, the company said that it would redesign its Champion stainless-steel stent and the "up to six months" delay that it anticipated for the program in May (Cardiovascular Device Update, June 2004) has now turned into a six- to eight-month delay, causing speculation among many analysts that the device will not launch in the U.S. until 2007. Guidant said it expects to file an investigational device exemption (IDE) application with the FDA in the first quarter of next year, and plans a European launch of the system in mid-2005.

"I am confident in the Champion program and it remains our lead drug-eluting stent program," Guidant Chief Operating Officer Guido Neels said during the conference call. He said the company has identified the issues related to manufacturing and stent design, and has solutions that are already being implemented. As in the company's last communique, Neels emphasized that the safety and efficacy and the clinical data of the bioabsorbable polymer and the everolimus drug remain "excellent." Guidant also said it is refining its processes to support large-scale manufacturing of the device.

The delay could mean the company faces being displaced as the third player in the U.S. drug-eluting stent market, behind Cordis and Boston Scientific. Medtronic (Minneapolis, Minnesota) reported in late May that it is "on track" with its timeline for commercialization of its Endeavor DES system, with European approval expected late this year and FDA approval for sale in the U.S. foreseen about a year later. The Endeavor system includes the Driver coronary stent, the ABT-578 drug licensed from Abbott Laboratories (Abbott Park, Illinois) and a phosphorylcholine coating owned by Biocompatibles, a unit of Abbott.

In some positive news, Guidant reported that U.S. and European regulatory agencies agreed to its plan to forgo additional clinical testing after it redesigns its stainless-steel stent platform. The company said the safety and efficacy of the coronary stent system has been supported by 12-month clinical data reported in its FUTURE I and FUTURE II trials, which qualify the product for European approval. However, Guidant still will need to complete its FUTURE IV trial for approval in the U.S.

Additionally, Dana Mead Jr., president of Guidant's Vascular Intervention division, noted during the conference call that the problems associated with the Champion do not effect the company's other DES program involving the Multi-Link cobalt-and-chromium stent. "The challenges that we are addressing with the Champion system do not impact our SPIRIT Vision-based drug-eluting stent program." He said that program "continues to progress on schedule" and if the SPIRIT FIRST trial results are positive, the company plans to initiate European and U.S. pivotal trials in 1Q05. The company expects SPIRIT FIRST six-month clinical results to be available in 4Q04.

During the call, some analysts expressed concerns that Guidant was spreading itself too thin in trying to maintain concurrent pivotal trials (for Champion and Multi-Link), not to mention enrollment for other companies' DES products – including Boston Sci, Abbott and Conor Medsystems (Menlo Park, California) – occurring at the same time. "If you think about just the numbers – a million cases [of restenosis] in the U.S., a million and a half stents being implanted – to enroll a few thousand patients shouldn't be overly difficult," Mead said.

VNUS tests IPO waters

VNUS Medical Technologies (San Jose, California) is the latest device firm to sample the initial public offering (IPO) waters, filing a registration statement with the Securities and Exchange Commission in late July for a proposed IPO of up to $80.5 million in common stock. At press time, the company had not set a number of shares or a per-share price for the offering. VNUS said it would commence the sale "as soon as practicable" after the registration statement is declared effective. The company's SEC statement reported that about $20 million in proceeds will be used for sales and marketing work; about $6 million for clinical research and product development; and the remainder for working capital and general corporate purposes. The underwriters of the offering will be Banc of America Securities and Piper Jaffray & Co., acting as joint book-running managers, and William Blair & Co., acting as co-manager.

VNUS manufactures devices for the minimally invasive treatment of venous reflux disease, a progressive condition caused by incompetent vein valves in the leg and characterized by leg pain, swelling, fatigue, skin ulcers and painful varicose veins. VNUS's Closure system for treating this condition consists of a radio frequency (RF) generator and disposable endovenous catheters, is used to close diseased veins through the application of temperature-controlled RF energy.

The company reports that its studies indicate about 25 million people in the U.S. and 40 million people in Western Europe suffering from venous reflux disease and the attendant painful symptoms. A company-commissioned study, it said, indicates that about 1.2 million people in the U.S. seek treatment for symptomatic venous reflux disease seek treatment annually, of which more than 800,000 exhibit saphenous vein reflux.

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