Cordis gains FDA panel support for pioneering carotid stent device

Finally some good news for Cordis. An FDA advisory panel late last month recommended approval of a carotid stent system and embolic protection device called the Cordis Carotid System. The device, the first system of its kind to be recommended for FDA approval, is intended as a minimally invasive alternative to carotid endarterectomy in high-risk patients.

The Cordis Carotid System is intended to improve blood flow to the brain while helping to prevent debris dislodged during the stenting procedure from entering cerebral circulation. The Precise carotid stent acts much like any other such device to improve flow past a lesion in the affected blood vessel. The Angioguard Emboli Capture Guidewire System extends beyond the lesion, opening into a tiny perforated basket, which catches plaque particles, yet allows continuous blood flow. After the stent is implanted to hold the artery open, the protective basket is closed and removed through the delivery catheter.

"The review panel's recommendation is an important step toward our goal of providing a safe, effective treatment alternative for patients with carotid artery narrowing who are at high risk for surgical treatment," said Dr. Guy Lebeau, a Johnson & Johnson group chairman with worldwide management responsibility for Cordis.

Whether the FDA will follow recommendations by its Circulatory System Devices Panel is anything but certain, given the narrow six to five vote. The panel's positive finding, however, provides a much-needed boost to a company that has been battered lately by a stream of political and legal problems.

In late October, the FDA issued a warning that the company's drug-eluting Cypher stent, which the agency approved in April 2003, might cause clotting and death (SCAN 11/12/03). By the time the FDA issued its warning, Cordis, a subsidiary of Johnson & Johnson, had shipped about 450,000 such stents. They had been implanted in 300,000 patients, about 60% of them in the U.S.

In late November, the FDA updated and clarified its position on the Cypher stent, emphasizing that it considers the drug-eluting device safe and effective when used according to the labeling. The rate of thrombosis, according to the agency, is within the expected rate for any stent. By Nov. 21, however, more than 360 cases of thrombosis had been documented in patients receiving the stent, resulting in more than 70 deaths. The agency has also received dozens of reports of possible hypersensitivity reactions, some leading to death.

These were enough to trigger a raft of class action suits. Then, on April 1, the FDA announced that Cordis had violated certain Good Manufacturing Practices at various facilities that manufacture the Cypher stent.

The FDA and Cordis must still address the GMP violations, which may have an impact on when the carotid stent reaches market. Of greater concern, however, is the narrow margin by which the advisory committee recommended approval. Safety concerns drove the close vote, and the panel named several conditions for approval: strict eligibility criteria for patients receiving the device, postmarket patient review, and measures to ensure the appropriate use of the system's distal protection device, so as to minimize the risk of stroke.

The panel based its positive recommendations on data from the SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) Trial, which indicated that the Cordis device is safer than surgery.

"Everyone receiving stents in the trial fared well. But what was impressive was that a subgroup of diabetic patients did extremely well and the surgical group did worse," said Dr. Mark H. Wholey, chair of the Pittsburgh Vascular Institute at the University of Pittsburgh, who presented the data at the Society of Interventional Radiology meeting in Phoenix.

Like many clinical trials, SAPPHIRE included patients with serious medical complications. Patients testing Cordis' new device had congestive heart failure or known severe left ventricular dysfunction, were scheduled for open heart surgery within six weeks, had a recent myocardial infarction, or had recurrent stenosis following endarterectomy. Anatomic indications included patients who are symptomatic with greater than 50% stenosis or asymptomatic with greater than 80% stenosis, both measured by ultrasound or angiography.

In making its recommendation, the panel suggested that candidates for carotid revascularization with the device have medical or anatomic high-risk indications as defined in the SAPPHIRE Trial. The second condition is to warn patients that if distal protection with the device cannot be deployed, the risk of performing the stenting procedure may be higher. The third calls for better patient education. The fourth asks for an independent neurological assessment at 30 days for the postmarket assessment follow-up group.