By DON LONG
Medical Device Daily Executive Editor
and AMANDA PEDERSEN
Medical Device Daily

The second-generation of drug-eluting stent (DES) technology is now reality in the U.S.

Medtronic (Minneapolis) on Friday reported FDA approval of the Endeavor DES, making it the first in the DES 2.0 family of these devices to win marketing approval in the U.S.

The stent, coated with the drug zotarolimus, may be one of the most closely watched devices in recent memory both clinically and financially — given its opportunity for elbowing aside the first-generation products, the Taxus, made by Boston Scientific (Natick, Massachusetts) and the Cypher, made by Cordis (Miami Lakes, Florida), a subsidiary of Johnson & Johnson (New Brunswick, New Jersey).

Both the Taxus and the Cypher while initially rushing to about $5 billion in combined sales have experienced stagnant to sagging sales as the result of negative clinical data, and a series of reports putting questions in the minds of doctors and patients concerning the overall value of DES devices and stenting in general.

The Endeavor received a panel recommendation for approval in October, and the Xience stent from Abbott (Abbott Park, Illinois) is expected to be the next to win approval, having received a positive panel recommendation in early December.

Now that Endeavor is approved for sale in the U.S., Medtronic is not wasting any time making the stent available to physicians.

Scott Ward, president of Medtronic's CardioVascular business, told Medical Device Daily on Friday the company would be initiating shipments over the weekend to begin commercialization today.

"We will be shipping about 100,000 units to U.S. hospitals in the next 30 days to assure full availability," Ward said.

Medtronic is anticipating a "blockbuster demand" for the Endeavor stent, he added.

The panel recommendation for Endeavor approval was based on a wealth of information supplied by the company, including data from seven clinical trials — three of these randomized controlled trials — for more than 2,200 patients, plus data from registries.

At the October meeting, panel members voted unanimously to recommend approval, contingent on post-approval enrollment of 5,000 subjects for five years to check for very late stent thrombosis as a primary endpoint, and death from myocardial infarction as a secondary endpoint, all in a single-arm registry. The panel also recommended that the label list the latest recommendations by the American College of Cardiology (Washington) and the American Heart Association (Dallas) regarding dual antiplatelet therapy.

As part of the FDA approval, Ward said Medtronic agreed to conduct a 2,000-patient post-approval study in the U.S., combined with another trial outside the U.S. with 3,300 patients. In addition, he said, the company plans to collaborate with FDA to conduct a trial intended to identify the optimal duration of dual antiplatelet therapy following angioplasty and Endeavor DES placement.

Medtronic said in a statement that "Ultimately, the ENDEAVOR clinical program will enroll more than 22,500 patients followed to five years." It said that more than two-thirds of enrollees will be implanted with the Endeavor.

The company said FDA approval of the Endeavor was based "on the most compelling and comprehensive body of scientific evidence submitted to the FDA" for a DES, "including more than 4,100 patients, followed up for as long as four years."

It said that the research showed "that Endeavor provides a consistent and sustained reduction in the need for repeat procedures compared to a bare-metal stent [BMS], while also maintaining an excellent safety profile."

In the same statement, Medtronic provided endorsement of the Endeavor stent by Martin Leon, MD, professor of medicine at Columbia University Medical Center (New York), cardiologist at New York-Presbyterian Hospital/Columbia University Medical Center, and principal investigator of the ENDEAVOR III and IV clinical trials. Leon, from the initial conception and development of DES technology, has been one of its proponents, calling the technology "game-changing" in the cardiovascular arena.

"Endeavor represents a true next-generation drug-eluting stent because of its unique design, which combines an advanced stent platform with the potent drug zotarolimus and a biocompatible polymer," Leon said. "This device addresses an important need by demonstrating comparable clinical effectiveness to a first generation drug-eluting stent while also exhibiting a safety profile more typical of a bare-metal stent, long considered a benchmark for safety performance."

He touted the Endeavor as being "exceptionally easy to deliver through the tortuous vessels of the coronary vasculature."

Presented at the October panel meeting, an analysis of pooled safety data from the ENDEAVOR clinical program reported a stent thrombosis rate for Endeavor patients of less than 1% within the first year, and a 0.08% rate from one year to three years, post-implant.

The same analysis revealed low cumulative rates of all safety measures out to three years of follow-up: stent thrombosis (0.7%); myocardial infarction (2.7%); and cardiac death (1%).

The company said that Endeavor "has shown numerically fewer adverse events across all key safety measures vs. a bare-metal stent. Of particular note from this analysis, just 3.5% of Endeavor patients experienced cardiac death or myocardial infarction through three years of follow-up, compared to 6.6% of patients who were BMS-implanted."

ENDEAVOR IV, a randomized controlled trial comparing the Endeavor stent with the Taxus stent, met its primary endpoint, with a target vessel failure (TVF) rate in Endeavor patients of 6.6% at nine months. The TVF rate for Taxus patients at nine months was 7.2%.

Endeavor had similar efficacy compared to Taxus for all lesion subsets analyzed, and there were no statistically significant differences in target lesion revascularization (TLR), a clinical measure for repeat procedures.

Compared to a BMS in ENDEAVOR II, Endeavor had fewer repeat procedures by more than 61% at nine months. This treatment effect is sustained, with only 7.3% of Endeavor patients in this randomized controlled trial requiring a repeat procedure out to three years of follow-up.