Medical Device Daily Washington Editor

WASHINGTON — The market for stents is probably large enough by now to qualify as an industry unto itself. But with Endeavor, made by Medtronic (Minneapolis), looking like a sure PMA winner, and the Xience (made by Abbott Labs (Abbott Park, Illinois), on the horizon, observers may be questioning whether this sector can absorb any more of these devices.

Xtent (Menlo Park, California) hopes to prove these observers wrong.

The firm’s NX stent and stent delivery system is designed to allow the placement of multiple stent segments in one catheter insertion. And if the drug used on the NX holds up in trials, it could grab significant share in this potentially crowded field.

NX uses a biolimus-coating on a cobalt chromium frame with a polylactic acid polymer as the medium of bonding and elution, crafted in 6 mm segments. The stent segments are locked at the ends until a collar near the tip of the catheter separates them, so they can be laid end-to-end for a variety of lengths as an alternative to overlapping multiple individual stents. The catheter also carries an adjustable-length balloon to account for the different deployment lengths and to vary the diameter of expansion within a stent.

Presenting data for the NX, Pieter Stella, MD, the director of cardiovascular research at the University Medical Center Utrecht (Utrecht, the Netherlands), said that initial trials for conventional stents have “excluded patients with multi-vessel and diffused disease.” And he noted that treatment of multi-vessel disease, one stent at a time, increases follow-on radiation exposure and often entails the use of overlapping stents.

Overlap, he said, is thought to encourage thrombosis, delayed endothelialization and non Q-wave infarction.

Studies of Xtent’s devices, in the Custom trials, he said, “were the first controlled evaluation of multiple and long lesions” and “angiographic results confirm efficacy.” Custom II, a 100-subject, first-in-man trial — with one year of follow-up — consisted of 69 patients with single lesions of 20 mm or longer and 31 patients with multiple lesions.

None of the two-lesion patients died of cardiac events in the first year, but one long-lesion patient died within the first six months. Four of the patients in the long-lesion group experienced infarction (two each for Q-wave and non Q-wave) in the first six months, but no other cases occurred in either group out to one year.

Compared with data from the Taxus V and VI studies, the NX fared well. Major adverse cardiac events occurred in 9% of the Custom II patients, vs. 20% and 16% rates, respectively, among patients in the Taxus V and IV trials up to a year. Target-lesion revascularization rates also favored the Custom II trial, at 4%, compared to Taxus V and VI, at 12.6% and 6.9%.

Stella said these numbers “demonstrate the safety of in situ customization to treat complex coronary lesions with a single catheter insertion,” and that confirmatory studies “to test the safety and effectiveness of the Custom NX DES System in a wide range of patient populations, are underway.”

Custom III is a safety trial of 90 patients, now fully enrolled; Custom IV will be the first of three trials that will randomize 2,500 patients and will add registry data in pursuit of a PMA.

Medical Device Daily interviewed Greg Casciaro, CEO of Xtent at Transcatheter Cardiovascular Therapeutics 2007. He said that Xtent has not selected a DES for the control arm of for Custom IV, in part because Medtronic’s Endeavor may soon be approved in the U.S. “We don’t have an official decision yet, but it will be an approved DES,” he said.

Medtronic’s data for the Endeavor included controlled trials and registries for roughly 25,000 patients, and the company was still required to meet with the FDA’s circulatory systems panel. Casciaro said he is comfortable with a pivotal trial population of 2,500.

Will the company need more subjects to nail down a PMA? “Anything’s possible” but “not likely,” he said. “The number is a solid one.”

Xtent will follow patients for five years-plus, but Casciaro noted that “the bar has been high since we started the dialogue with FDA,” and he expects no significant FDA changes regarding pivotal trial enrollment requirements.

Casciaro said he is not concerned that DES market saturation.

“For us, it doesn’t make a difference... this is a leapfrog product that will allow doctors to customize care by customizing the product in situ,” and enabling surgeons to fix the stent with full apposition into the vessel wall. He called these “giant leaps that will revolutionize this care” and differentiate the company’s product.

“I think that doctors do articulate a desire to see a different form of care,” he said, and thus see the NX as enabling them “to customize care. I think they’re very excited about the delivery system.”

As continued patient fears of DES, Casciaro said, “the past year has been a deep gulp of air” regarding DES, but “people understand that even in off-label use, they perform as well as or better than bare metal.”

And he noted that both the Journal of the American Medical Association and the New England Journal of Medicine have acknowledged that their DES reports lacked balance.

Casciaro also said he is confident that NX will not produce the adverse events in the treatment of multi-vessel disease associated with current DES problems because “we have a very unique platform... that will avoid the need to overlap stents” — which he described as short and stiff — “and the reduction in the amount of exchanges [reinsertions].”

NX also avoids the malapposition pockets responsible for a portion of the late stent thrombosis. “What today takes multiple stents and multiple balloons and insertions, we do with one insertion.”

Xtent went public in February, its shares currently trading for a lot closer to its 52-week low of $7.46 than the high of $17.24.

Regarding the possibility that the DES market is too crowded for Xtent to sell more shares or obtain equity funding, Casciaro said, “interventional cardiology is the No. 1 device market in the world. If you have innovation, there is money out there.”

And he noted that heart disease is a downstream effect of diabetes and obesity, and “there’s no pill that I’m aware of” to cure either condition. But he would not go on record as saying that further stock sales or private equity funding would serve as the bridge to market, though “the returns are available.

Two companies are producing more than $4 billion in revenues” from coated stents, he noted, and he is further buoyed by the fact that multi-vessel disease is the norm rather than the exception.

Pricing strategy, he said, “will be to charge for more than one stent but less than two.” Given the frequency of multi-vessel occlusions, “it will always be at least not an objection” for the payer and the hospital to choose the NX, which he said “will fall under an existing DRG.”