Cordis (Miami Lakes, Florida) reported Thursday that the FDA has notified the company that all items outlined in an April 2004 warning letter regarding its Cypher drug-eluting stent (DES) have been resolved.

The warning letter addressed what it called violations of the Federal Food, Drug and Cosmetic Act, noting that the agency was “concerned with the breadth and scope of the specific violations,” which the letter indicated were “symptomatic of the serious underlying problems in [the] firm’s manufacturing and quality systems.”

Cordis company spokesman Christopher Allman told Medical Device Daily that the resolution of the FDA’s concerns outlined in the warning letter represented a “tremendous achievement” for those employees who had been devoted to ensuring that the company met agency requirements.

“If you look at the warning letter itself ... really the issues fall into the bucket that we would call processes and procedures,” Allman said.

Allman acknowledged that “a lot of internal resources” had been focused on resolving the warning letter. More importantly, the company could not proceed with next-generation products or apply for new indications for its Cypher stent.

The warning letter, which came as a result of agency inspections, outlined problems such as failure analysis reports relating to Cypher thrombosis complaints not having been “completed in a timely manner,” because the company failed to “establish and maintain adequate complaint handling procedures.”

The agency specifically cited a complaint related to the Cypher stent involving a “thrombosis event” that was received on June 30, 2002 but was not closed until June 20, 2003.

“The FDA inspections found systemic violations in the quality management system employed to sure the safety and effectiveness of your drug-eluting stents that recurred at several of your facilities,” the agency said in its letter.

The agency also cited “several hundred complaints” that were received in 2002 and 2003 through an Internet-based tracking system used by physicians to report complaints and adverse events that had not been “fully investigated at the time of the inspection.”

The sites specifically mentioned in the letter were San German, Puerto Rico; Warren, New Jersey; Roden, the Netherlands; and Beerse, Belgium.

Despite the warning letter, Cordis was able to get approval for its treatment for clearing clogged neck arteries, a leading cause of stroke, in September (Medical Device Daily, Sept. 29, 2006). Johnson & Johnson (New Brunswick, New Jersey) reported at the time that its Cordis Endovascular (Warren, New Jersey) unit received approval for its Precise carotid stent and Angioguard system following receipt of an approvable letter in August 2004 after receiving an okay from the Circulatory System Devices Panel of the Center for Devices and Radiological Health in April 2004 (MDD, April 23, 2004).

Bear Stearns analyst Rick Wise said in a report that in that firm’s view, “the warning letter stymied, in particular, Cordis’ DES pipeline. J&J, Wise noted, was restricted from gaining premarket approvals for new products, although it was “still able to launch products that required a 510(k).”

“Longer-term, resolution of Cordis’ warning letter may not be positive for competitors” such as Boston Scientific (Natick, Massachusetts), Abbott (Abbott Park, Illinois); and Medtronic (Minneapolis). Still, he cited the lack of a “visible near term JNJ pipeline and CoStar delays” as indications that the “DES competitive outlook is unchanged for the next 3-5 years.”

Still, according to Wise, it had not been anticipated that the warning letter would hold up “the expected [nine] Cordis product launches in 2007,” which includes balloons and guidewires.

The good news, Wise noted, is that resolving the warning letter “should allow Cordis to redeploy resources more aggressively into pipeline-building.”

Last month, Conor Medsystems (Menlo Park, California), which was acquired by J&J in February for $1.4 billion (MDD, Feb. 5, 2007), reported that its pivotal trial for the CoStar paclitaxel drug-eluting (DES) stent failed to meet its primary endpoint of non-inferiority to Boston Sci’s Taxus Express 2 stent (MDD, May 8, 2007).

Conor also reported at the time that it will continue to develop another stent, this time using sirolimus, the drug used in the Cypher stent. Conor has indicated that the CoStar stent’s unique design demonstrated an improvement in the elution of drugs used with stents, and as possibly a way to avoid problems that have come to light relative to the once-bannered DES products.

“The potential of this platform remains to be realized,” said Nicholas Valeriani, worldwide chairman, Medical Devices and Diagnostics, for J&J, during a conference call at the time. He also said that J&J is “optimistic that a compound like sirolimus will enable us to capture that potential.”

“This was an investment in the long-term, and we continue to have great enthusiasm for the promise of this stent platform in combination with the work that we’ve done at Cordis to create what we think will be truly the next generation of drug-eluting stents for patients with coronary disease,” Valeriani said.

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