Medical Device Daily Contributing Writer

BARCELONA — Valve replacement is the new frontier for minimally invasive coronary interventions and three companies have emerged as front-runners in the race to stake out a claim of a market that senior executives from each company described, in a word, as “huge.”

CoreValve (Irvine, California) won the pole position, in mid-May reporting receipt of a CE Mark for its transfemoral percutaneous aortic valve replacement device (Medical Device Daily; May 21, 2007).

Rob Michiels, COO of CoreValve, told Medical Device Daily at last month’s EuroPCR meeting here that the company would soon file for an Investigational Device Exemption from the FDA and expects to start a pivotal trial for pre-market approval before the end of this year.

Founded in 2001 by noted French interventional cardiologist Jacques S guin, MD, who serves as CEO and chairman, privately held CoreValve raised $33 million in March (MDD; March 29, 2007) to underwrite product and market development.

Edwards Lifesciences (Irvine, California) is the heavyweight in the field, with a 30-year track record and enrollment under way since March for a pivotal trial totaling some 600 patients. Edwards expects to receive CE-marking for its transfemoral device by year-end.

The dark horse in the race is JenaValve (Munich, Germany), which just weeks ahead of the EuroPCR gathering — Europe’s largest interventional cardiology event — reported that it had secured 13.5 million ($4.8 million) and put its management team in place. Offices were moved from Germany’s innovation hotbed in Jena to a corporate center in Munich.

JenaValve brings to market a unique anchoring stent for valve placement compared to what it termed the “passive” anchors of its competitors that it said risk “mispositioning.”

CEO Helmut Straubinger told MDD, “This is a very high-potential market with only a few competitors and a lot of ideas. We expect a $2 billion market share among industrial countries, where the total [global] market today is $2.1 billion.”

A sign of the growing interest among interventional cardiologists in this emerging practice area could be seen at the EuroPCR meeting, where valve and non-coronary cardiac disease was one of four dedicated tracks offering four days of courses, lectures and live demonstrations. This year’s EuroPCR gathering also incorporated the Transcatheter Valve Symposium, which until this event, had only been held in the U.S.

“Heart valves is a dynamic research and development area, as a total of 35 companies are currently working in this area,” said Philipp Bonhoeffer, professor and chief of cardiology at the Great Ormond Street Hospital for Children (London) and chairman for several percutaneous valve plenary sessions at EuroPCR.

(For a discussion of issues and opportunities in the field of heart valve repair or replacement, see Cardiovascular Device Update, April 2007.)

“Here is where the frontier lies,” said CoreValve’s Michiels at EuroPCR, quickly sketching a pie chart divided into three wedges. “The market is going to split into three approaches for intervention — open-heart surgery, transfemoral catheter and transapical catheter. The challenge is to know what will be the size of each of these pieces of the pie.”

He added, “Everyone needs to answer that question, and we already know where we want to go,” noting that the funding received in March accelerated CoreValve’s development of a transapical transcatheter device (see story, page 9).

In March, Edwards began enrollment for a pivotal trial that seeks 600 high-risk patients over the next 16 months. Among 350 operable patients, a 1-to-1 randomization will test open-heart surgery against the Edwards Sapien valve. For 250 patients who are judged unable to withstand surgery, the randomized trial will test medical management against the non-invasive transcatheter Sapien valve. All patients will be followed for one year.

For CoreValve’s part, Michiels said the CE mark “changes our world. It is a validation of the technology, a validation of the procedure. This is no longer an investigation.”

CoreValve is past the halfway mark for enrollment in a Phase III international clinical trial using the first-to-market ReValving System.

The valve has been successfully placed in 30 patients in the safety and efficacy trial that will enroll 100 patients at 12 sites in Europe and Canada.

“Accomplishing percutaneous replacement of an aortic heart valve in a cath lab setting, in about 10 minutes excluding prep time, without any assistance whatsoever to the beating heart, is why ReValving has such incredible potential for non-surgically treating the thousands of patients who have diseased aortic heart valves but who are just too fragile to undergo open-chest surgery,” said CoreValve’s S guin.

JenaValve’s Straubinger said the company successfully placed its valve temporarily in one patient to test positioning technique. The valve and stent were then removed, demonstrating the system’s unique retraction feature.

Straubinger said 15 patients are enrolled for a valve replacement and that he expects the company will begin clinical trials by the first of the year. JenaValve expects to receive a CE mark by early 2009 for its transarterial aortic heart valve replacement (AVR) system, including a self-expanding nitinol stent bearing a biological valve.

“The highest risk for this procedure is mispositioning of the valve,” he said. “With a beating heart, there is constant movement.”

Straubinger pulled from his coat pocket a steel rod and demonstrated the technique of using what he called a double paper clip device to anchor the new valve to the aorta ascendens. “This is a very smart, safe and secure manner of placing the valve in the cusps of the old aortic valve,” he said, expanding and collapsing the device.

“The cardiologist can feel the stent lock into place, or if he has any doubt, he can retract the assembly back into the tip either to reposition or to remove it entirely,” he said.

The procedure requires 10 minutes of preparation, about one minute for the valve to be clipped into place, and then 10 minutes for closure, he said.

“What valve the cardiologist chooses is not as important as how the valve is secured,” he said, adding there are 340 different porcine, bovine and equine valve types in the market. “We recently heard of one procedure using tissue from a kangaroo.”

Straubinger agreed that the pie chart is going to become much larger, predicting market development over the next eight years. “This is a true safe alternative to conventional surgery, especially for elderly patients suffering from co-morbidity,” he said. “As the JenaValve system becomes the procedure of choice, we expect its benefits will become equally attractive to many other potential patients.”

JenaValve investors established a U.S.-based holding company, Jencardiotec (Wilmington, Delaware), but Straubinger said that a move into the U.S. market “is a strategic decision we have not made yet and requires FDA approval. We are starting in the CE mark-countries and will collect the data.”

Michiels said that concurrent with clinical trials and approvals, CoreValve is “working on reimbursement country-by-country.” Adding what device makers have learned from much hard experience: “Winning reimbursement for the procedure is as difficult as earning approval for the product” and also: “It is even more difficult where there are no comparatives.”