Citing issues related to potentially sub-optimal dosing of paclitaxel, Conor Medsystems (Menlo Park, California) reported that its pivotal CObalt Chromium STent with Antiproliferative for Restenosis (COSTAR II) trial for the CoStar drug-eluting stent (DES) failed to meet its primary endpoint of non-inferiority to Boston Scientific's (Natick, Massachusetts) Taxus Express 2 stent with respect to major adverse cardiac events (MACE) in patients with multi-vessel or single-vessel disease.

The result is a large setback for Conor and also a fairly large negative for Johnson & Johnson (New Brunswick, New Jersey) which acquired Conor in February for $1.4 billion (Medical Device Daily, Feb. 5, 2007) in an attempt to augment its offering in the DES market — specifically, the Cypher stent made by J&J subsidiary Cordis (Miami Lakes, Florida).

Conor said it will immediately terminate ongoing clinical trials for the CoStar stent and will not proceed with submission of its premarket approval application to the FDA.

Additionally, the company said it will discontinue sales of the CoStar through its partners in certain countries in Europe, Asia and Latin America where the CoStar stent is already approved. It said it will work with those partners to facilitate return of product in inventory in customer accounts.

In a conference call on the trial termination, Campbell Rogers, MD, chief technology officer, cardiovascular franchise for Conor, said the eight-month MACE rate for the CoStar DES was 11% vs. 6.9% for the Taxus, which also elutes paclitaxel.

"This difference did not meet the pre-specified definition of non-inferiority for the CoStar stent," said Rogers.

The company also failed to achieve non-inferiority for in-stent late loss (0.48mm for CoStar vs. 0.15mm for Taxus). Additionally, target vessel revascularization was 8.1% for CoStar vs. 4.3% for Taxus, with CoStar demostrating six thrombotic events (five within 30 days, one beyond 30 days) vs. one for Taxus (0 within 30 days).

Rogers said the company attributes the trial failure to the "very low doses of [paclitaxel] that were chosen to be delivered by the CoStar stent."

Conor said it will continue to develop another stent using its unique design — an architecture that includes hundreds of small holes to deliver the drug — but will use sirolimus, the drug employed in J&J's drug-eluting Cypher stent.

Conor has bannered the architecture of the Costar as an improvement in the elution of the drug, and as perhaps a way to avoid the problems seen in other DES products.

While expressing disappointment at the result of the trial, Nicholas Valeriani, worldwide chairman, Medical Devices and Diagnostics, for J&J, said during the call that his company is still excited about Conor's technology and its future prospects.

"The potential of this platform remains to be realized," said Valeraini, "and we are optimistic that a versatile 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."

Rick Anderson, J&J's company group chairman and worldwide cardiovascular franchise leader, 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."

Dominic Caruso VP finance and CFO of J&J said that the company still expects that 2007 EPS guidance of $4.02-$4.07 will remain unchanged despite a 2 cent-3 cent EPS impact from the discontinuation of CoStar sales in Europe, Asia, and Latin America.

Analysts said the real impact here will be the company's inability to launch a new product in a timely fashion, giving competitors a leg up.

Rick Wise of Bear Stearns (New York) wrote in a research note that because of the FDA's concerns regarding DES and the likely repercussions for new stent approvals, "this could push a Costar launch out three to four years, possibly in the 2010/2011 timeframe."

He said he expects Abbott Laboratories (Abbott Park, Illinois), Boston Scientific and Medtronic (Minneapolis) to benefit — in that order — from the delay.

Banc of America (New York) analyst Glenn Novarro called the failed trial a "definite setback" for J&J and a "psychological positive" for its stent-making rivals.

"Based on our global drug-eluting stent market projections, by removing CoStar from our models, we estimate that approximately $75 million in drug-eluting stent sales will be up for grabs in 2007 and approximately $200 million in 2008," he wrote in a research note.

The company said that additional data from the failed pivotal trial will be presented at the upcoming EuroPCR meeting to be held May 22 to 25 in Barcelona.