An FDA advisory panel gave its unanimous backing to the second in what is likely to be a lengthening line of premarket approval (PMAs) applications for drug-eluting stents (DES). The nod went to the Taxus paclitaxel-eluting coronary stent from Boston Scientific (Natick, Massachusetts). The approvable vote at the late-November meeting came with conditions, notably in labeling. The labeling should indicate that plavix, or plavix and aspirin, be continued for six months following stent implant, the panel said. Additionally, the labeling should include a precaution concerning potential interactions with other DES devices. An additional condition stipulated that an implied comparison that the stent "reduced restenosis" should specify that the comparison was with an uncoated, or bare-metal, stent. Boston Scientific's stent would be indicated for patients with de novo coronary artery lesions with a length equal to or less than 28 mm and vessel diameters ranging from 2.5 mm to 3.75 mm. If the device receives final approval, it will go up against the Cypher stent from Cordis (Miami Lakes, Florida), the first company to receive clearance for a DES product in the U.S.
For its premarket approval application, the company primarily used data from the U.S.-based TAXUS IV study utilizing the Express stent with a slow release formulation of paclitaxel. Results of the TAXUS IV trial were presented to the panel by Gregg Stone, MD, director of cardiovascular research and education at Lenox Hill Heart & Vascular Institute (New York) and the principal investigator of TAXUS IV. The trial included 1,326 patients at 73 U.S. sites with de novo lesions coverable by one stent. Patients were randomized to either the drug-coated stent or uncoated stent and tracked using serial numbers, so that neither physicians nor patients knew which stent they received, Stone noted. About 98% of the patients received one study stent, but the other 2% received a study stent and non-study stent, Stone explained. "The vast majority of patients received one study stent," he said.
The primary endpoint of total vessel revascularization was met, Stone said. Adverse events and stent thrombosis rates between the drug-eluting and bare-metal stents were comparable at nine months, with less than 1% of patients having thrombosis and no cases of thrombosis reported later in the study, he explained. "We're committed to following up with patients on thrombosis," said Mary Russell, MD, of Boston Scientific. "We've had a total of 47 reports of thrombosis out of more than 75,000 implanted stents sold." She added: "Taken together, the data demonstrates safety and effectiveness and the benefit of the Taxus stent outweighs any risks."
Jennifer Goode, a biomedical engineer and lead reviewer at the FDA's Center for Devices and Radiological Health for the Boston Scientific PMA, explained the status of the application to the panel. "The PMA was filed in June, and a major deficiency letter was sent to the sponsor in September requesting additional data," she said. The company responded and continues to resolve outstanding issues, Goode noted. "The biggest outstanding non-clinical issue we are currently working on with the sponsor is the stability and shelf-life testing for the PMA," she said.
Christopher White, MD, of the Ochsner Clinic (New Orleans, Louisiana), said during the panel's initial discussion of the Taxus stent, "I want to congratulate the sponsor on how the clinical trial was conducted. Boston Scientific did an excellent job of monitoring the investigators and ensuring that they were compliant." Panelist William Maisel, MD, of Brigham & Women's Hospital (Boston, Massachusetts), added that finding the right combination of drug dosage and delivery mechanism "is one of the biggest challenges in developing an effective drug-eluting stent. I'd like to take whoever came up with your choice of dosage with me the next time I go to Vegas."
The panel concurred that, while the data demonstrated safety at nine months, more long-term data are needed to assure stent safety, said panel chair Warren Laskey, MD, affiliated with the Uniformed Services University of the Health Sciences (Bethesda, Maryland). A proposed five-year follow-up period is a practical timeframe, he added. "Additional information that should be collected should be on what types of patients are receiving the stent and what kinds of interactions they develop."
Informing patients about potential drug interactions and hypersensitivity, especially in patients treated with chemotherapeutic agents, would be prudent, panelists said, but they stopped short of recommending a warning on the stent's labeling about such risks. Proposed labeling for the stent calls for the use of a single stent, with bailout stenting allowed, but should not state that it reduces restenosis, because effects may not be the same if another uncoated stent is used in conjunction with the Taxus stent. "That wording on the indications for use could lead to deceit," said Judah Weinberger, MD, of Columbia University (New York).
Although the FDA is not bound by the panel's vote, it usually follows the recommendations.
Edwards sheds Lifepath to sharpen focus
Edwards Lifesciences (Irvine, California) said during its 2003 Investor Conference on Dec. 9 that it plans to sell its LifePath AAA Endovascular Graft System in order to focus on its heart valve therapy devices and on catheters used to monitor heart performance during surgery. Abdominal aortic aneurysms (AAA) result from a bulging in the aorta, the major vessel that distributes blood through the body. Unlike traditional treatments, which require open chest surgery, the Lifepath system treats the aneurysm through a small incision in the leg. Edwards said it intends to explore "strategic alternatives" for the Lifepath system. The system, with employs a unique balloon-expandable design, is currently sold outside the U.S. and is in clinical trials in the U.S.
"The favorable clinical results we have experienced to date and the growing adoption of the device in Europe continue to support our belief that the Lifepath System can greatly benefit patients with AAA disease," said Michael Mussallem, chairman and chief executive officer. But he said that despite "encouraging results" and the clinical need for AAA products, "additional investment is necessary in order for it to attain a leading global position. By focusing our resources on fewer, high-potential initiatives, we believe we can improve their probability of success."
Edwards was forced to halt a clinical trial of the product in April 2000 after it was discovered that some of the wireforms of the graft material which covers the tubular body of the device had fractured. That discovery also resulted in withdrawal of the Lifepath system from the European market. The company received a CE mark for a relaunch of an improved version of the system in October 2001 and a clearance for a relaunch of its U.S. clinical trial that same month under an investigational device exemption.
Stuart Foster, corporate vice president, technology and discovery, said that while the device offers a "clearly differentiated product" from others on the market and has had encouraging clinical results including a 70% reduction in aneurysm sac size one-year post treatment, "there are substantial investments that are going to be required." For one, Foster noted that the company would still have to go though a U.S. premarket approval process. He also said that in order to remain competitive in the market, Edwards would have to incur continued development costs, "in terms of additional sizes, in terms of adapting our graft for supra-renal use probably adding an aorto uniliac graft as well as a thoracic graft." And lastly, he said the company will need to add a clinical specialist channel into the U.S. to introduce this product. "This is a product that requires quite a bit of training and specialist know-how and patient identification as well as in placement," he said.
The Lifepath system so far generates an estimated $4 million a year in sales. The company said it still plans to submit its final marketing application to U.S. regulators early next year and it expects to receive approval by the end of 2004.
Expressing surprise at the move to sell the Lifepath was Larry Haimovitch, president of Haimovitch Medical Technology Consultants (Mill Valley, California), who covers the cardiology sector for Cardiovascular Device Update. "To me, the AAA market still holds a lot of promise," he said, noting that Edwards was going to file its premarket approval application very soon and would have been in the market probably by the end of next year. "They have [previously] touted this as an important new area for them," said Haimovitch.
During the meeting, several initiatives were outlined that Edwards believes will drive sales growth and profitability in 2004 and beyond. Among the "more promising" programs, the company highlighted initiatives in its market-leading replacement heart valves and repair products. "This year, we have introduced an unprecedented series of new products, including Perimount Magna, Tricentrix and IMR Etlogix," Mussallem said. In addition to continued development of additional heart valve products with even greater durability and performance than those available today, Edwards said it is investing in several new interventional platforms that it said could "substantially expand" the heart valve therapy market. And just a few days after the investors' conference, it announced plans to acquire Percutaneous Valve Technologies (Fort Lee, New Jersey) in a $125 million deal (see Acquisitions, page 12).
Edwards also touted its peripheral interventions platform, with Mussallem noting that the peripheral stent market represents a "significant growth opportunity." He said the September introduction of its balloon-expandable LifeStent System represents the first in a series of new non-coronary stent offerings that the company expects to introduce over the next several months, including a flexible, self-expanding stent.
NeoStem unveils cardiac calculator
NeoStem (Agoura Hills, California), a new company focused on developing adult stem cell therapeutics, has unveiled its Cardiac Risk Assessment Calculator, designed to be a quick and convenient way for individuals to evaluate a possible increased risk of heart disease.
Requiring just a few minutes to complete, the calculator takes into account such risk factors as age, weight and smoking and alcohol consumption, among others, to make a determination of whether an individual is at increased risk. The calculator also enables users to analyze and educate themselves on behaviors that can contribute to an overall increased risk.