Medical Device Daily Washington Editor

WASHINGTON — Given the emphasis on minimally-invasive treatments in the cardiovascular sector, the market for percutaneous devices for the heart seems poised to grow even further. So it comes as no surprise when more companies want to move into the crowded stent market.

But placing a stent percutaneously is one thing. Replacing a heart valve percutaneously is quite another, and this sector still has far to go to catch up with stent technology.

Joining the chase for the first FDA-approved percutaneous valve replacement is Endovalve (Princeton, New Jersey), a company recently formed out of research from the University of Pennsylvania (UP; Philadelphia).

Edwards Lifesciences (Irvine, California), for many observers, is the favorite in this race, with its Sapien valve, but the Sapien is designed for aortic valve replacement.

Newcomer Endovalve has its sights set on No. 1 position for mitral valve replacement.

The firm in October reported completing testing on four sheep. Ultrasound imaging indicated that the valves functioned well "with acceptable mitral regurgitation" and secured adequately to the native annulus.

In a company statement, Howard Herrman, MD, chairman of Endovalve's scientific advisory board, said that thanks to the test results, "we can confidently say that the device stays in place and functions with little regurgitation." It noted also that the company had been working in "virtual" mode to minimize up-front costs by outsourcing much of the R&D to 20 engineers, some working out of UP labs.

As every good venture capitalist knows, management's track record says a lot about whether an upstart has a chance of successful lift-off.

That of Endovalve's president, Robert Wilkins, MD, is robust. He was in practice in anesthesiology and critical care, and he also held positions at Abbott Laboratories (Abbott Park, Illinois) and Baxter Healthcare (Deerfield, Illinois), and in "small start-up environments" as well, according to the company's web site.

Medical Device Daily talked with Wilkins during the Transcatheter Cardiovascular Therapeutics 2007 conference last week, and he expressed optimism about the company's prospects for prying open this percutaneous valve market space.

Endovalve leaflets are derived from bovine tissue, and he anticipates crafting valves in "at least two, probably three" diameters.

One of the issues routinely arising during hearings of the FDA circulatory systems advisory panel is whether there is a sufficiently large base of surgeons who are qualified to handle such a procedure.

Wilkins said that although they don't exist in large quantities, "the numbers are changing" — for the better.

The catheter that will deliver the valve is "very similar to the size you'd use to deliver an occlusion device," such as a stent, he said, suggesting no need for additional skills or significant additional training for delivery of a catheter up the femoral artery into the heart.

Wilkins said that there are "one or two [qualified surgeons] in every large hospital," and so lack of clinical expertise is no barrier.

Clinical trial enrollment requirements seem to be in flux of late. But Wilkins said that by "FDA's estimates, we're clearly going to need a minimum of 100 to 150 in each [study] group," with the study conducted in five to 10 centers.

But he also said that he "wouldn't' be surprised to see between 300 and 600 patients" by the time the company obtains final premarket application approval.

MDD asked Wilkins if the universe of interventionists currently skilled enough to tackle this device might already booked up with trials.

This might be a consideration, he said, if Endovalve were poised for a pivotal trial immediately.

Rather, "we're a couple of years away from starting, and by that time, many current trials will have moved on," he said, and that in two years, "there will be no shortage of cardiologists who want to try something different."

Wilkins hopes clinical trials outside the U.S. will be completed by 2009, with the firm obtaining the CE mark the following year.

As for a PMA, he pegged 2013 as being "as early as it could happen."

He said that the CE mark is meaningful in the context of getting clinical data for U.S. approval and reimbursement, but that Europe is not the major sales target. As in many other sectors, uptake in the U.S. market is the goal since usually matching that of the entire international market.

The problem of patients resisting enrollment randomization is "certainly going to be an issue," Wilkins acknowledged. He said that early patients will "be unfit for CABG" and thus likely to resist going into a medical therapy control arm. Larger trials would enroll patients into a control arm of treatment with an FDA-approved valve, implanted via thoracotomy.

As is well known, Medtronic (Minneapolis, Minnesota) had data from 25,000 patients from both registries and controlled trials for the Endeavor drug-eluting stent, but still had to go before an FDA advisory panel. But Wilkins said there is "no expectation we'll need that" amount of data for a valve.

Regarding reimbursement, Wilkins said that "the procedure can be done within an existing DRG," a reference to DRG 104, designated for cardiac valves and other major cardiothoracic procedures with cardiac catheterization (DRG 105 is the same set of procedures sans catheterization).

Endovalve came into being after an initial $2.5 million round of financing from Battelle Ventures (Princeton, New Jersey), and an affiliate fund, in the spring of 2006. Despite the hope of second-round financing earlier this year, Wilkins said "we decided to postpone our Series B" in favor of further benchtop work.

"We're now out raising our Series B" with $15 million as the goal.

As for the total cost of developing the valve and its delivery technology, Wilkins said he is "pretty confident" that the will be "in the $50 [million]-$60 million range."

"At the moment," he said, "we're seeing enough interest from venture capital funds" that could take the company through to product marketing.