Clinical trial testing of drug-eluting stent (DES) devices over the remainder of this decade will seek to assess new, more complex uses and outcomes.

Over the past four to five years, companies developing these ground-breaking devices have focused on demonstrating their superiority to bare-metal coronary stents, and have done so successfully. But now, the focus of trial attention will be on the best applications for these devices, in which patients they are best used, and whether advanced-generation DES devices – poised to enter the market – will be able to do more, and do it more reliably.

That is clearly the emphasis for Xtent (Menlo Park, California), developer of what it calls next-generation "customized" DES technology.

The company yesterday reported the first procedures in its CUSTOM II trial that is examining the ability of its system to do multi-vessel stenting and long lesion stenting as an alternative to the use of multiple stents. Key to this system is the use of a single stent train capable of deploying the DES into multiple placements or into long lesions without using several stents or several stents in overlapping fashion.

It reported that for the first time "in the history of coronary stenting," a single catheter was used to treat multiple lesions in multiple coronary arteries in a human patient. The company further announced that physicians have treated a second patient with "the longest coronary stent of any kind ever delivered with a single catheter."

The procedures were performed by Prof. Eberhard Grube, MD, chief of cardiology, Siegburg Heart Center (Siegburg, Germany), and principal investigator for Xtent's CUSTOM II clinical trial. Both procedures were important breakthroughs for what the company terms a one-catheter, "single-delivery strategy" and steps toward achieving U.S. and European regulatory clearances over the next two to three years.

For a developmental company, of course, the question is what can it bring in competition with the already-commercialized Taxus and Cypher stents and the others due to come online from the big players.

"We had to look out into the horizon," Greg Casciaro, president and CEO of Xtent, told Medical Device Daily, in answer.

What the company saw there, is the "more complex patient," he says, requiring "more than one stent" and the need for a simplified strategy that would conflate multiple procedures into a single placement procedure.

This strategy is demonstrated in the first two procedures of CUSTOM II.

In one patient with multi-vessel disease, Grube treated two separate lesions in different arteries during a single insertion of the Xtent system, customizing the length of each stent in situ to match the length of each lesion. First, a stent 28 mm in length was placed in a marginal branch artery. Then, without removing the device, it was repositioned to deploy a second 32 mm stent in the left anterior descending artery.

In another patient, Grube delivered a single 52 mm stent, the longest stent ever placed in the coronary arteries from a single catheter, Xtent said.

"Both cases were excellent examples of how one device can easily replace two or three standard drug eluting stents," said Grube.

Assuming eventual commercialization, this strategy means faster procedural time and a cost falling between that of one DES placement and two DES placements, Casciaro says, hence a significant reduction for placements of more than two stents.

This strategy, he adds, positions Xtent for addressing the more than 50% of procedures requiring multiple placements – and growing. And he suggests that as DES procedures continue to penetrate the traditional bypass procedural market used to treat more difficult disease, this "complex patient" market could grow to 80% of stent procedures, offering another possibility for expansion of the one-catheter approach.

Regulatory approvals aren't exactly imminent, however.

Casciaro says that regulatory filings for the CE mark could come in mid-2006, with approval by early 2007. Launch of a trial under an FDA investigational device exemption, currently being discussed with the FDA, he said, could lead to U.S. commercialization by 2009.

He reports that enrollment in the company's first trial, CUSTOM I, has been completed. Looking primarily at adverse events, data from CUSTOM I is likely to be ready for presentation at this year's meeting of the American College of Cardiology (Northbrook, Illinois) and at EuroPCR, he says.

The drug used in the Xtent system is Biolimus A9, together with a bioerodable (or absorbable) polymer, licensed from Biosensors International (Singapore/Newport Beach, California), together with a coating from a Biosensors subsidiary, Occam International (Eindhoven, the Netherlands).

With Biolimus, Casciaro says that Xtent is "smack-dab in the game with a drug of clinical efficacy that may be as a good as or better than what is currently available on the market today."

He says that much of the company's data concerning the efficacy of this drug use is being validated, or will be further validated, in its studies, but also backed in studies by Devax (Irvine, California) and Terumo (Tokyo), using the same drug.

But he emphasizes the deliverability feature of the Xtent system – which he calls "easy, fluid, efficient" – for the more difficult stenting issues is its main differentiator.

By comparison, he notes that in most DES stenting, the clinician makes a best "guesstimate" of what size DES to use. And he cites study figures indicating that up to 40% of current DES placements may involve placements of the wrong sizes."

Thus, he says, "The ability to customize to lesion length is something no one else can accomplish."

Growing out of the Foundry (Redwood City, California) medical device incubator, Xstent is funded by venture capital firms including Advanced Technology Ventures, Latterell Venture Partners, Morgenthaler Ventures and Split Rock Partners.

Xtent early last year closed on a $25 million round of financing.