Medical Device Daily Associate

After a few speed bumps along the way, it appears thatEdwards Lifesciences (Irvine, California) is back on track to get its percutaneous heart valve approved for use in the U.S.

The company yesterday reported that clinicians have completed 20 patient cases in the U.S. feasibility study evaluating use of its Cribier-Edwards percutaneous aortic heart valve. It also said that the FDA has approved expanding enrollment of the U.S. feasibility trial by an additional 35 patients.

The trial enrollment expansion is good news for the company which just under a year ago halted enrollment in a U.S. trial using the valve after it received reports of complications, including death, among some of the roughly 10 patients that had enrolled (Medical Device Daily, June 15, 2005).

“We're pleased to receive FDA approval to continue feasibility cases to treat additional patients with this important new technology,” said Stanton Rowe, president of Edwards' percutaneous valve initiatives, in a company statement. “We continue to believe that percutaneous therapies provide tremendous therapeutic potential, particularly for patients who are unable to receive treatment today.”

Edwards said it voluntarily postponed the earlier trial of the valve after some U.S. “antegrade” cases demonstrated a greater degree of clinical complexity and adverse outcomes when compared to results of a Canadian study, where cases were being performed with a new “retrograde” delivery system.

At the time, Edwards said that data presented at the 2005 EuroPCR conference indicated that the company's custom retrograde delivery system resulted in positive clinical outcomes in the Canadian trial.

The Cribier-Edwards device, which was developed by Edwards in conjunction with Alain Cribier, MD, chief of cardiology at University Hospital (Rouen, France), is designed to treat patients with severe aortic heart valve stenosis. Percutaneous heart valve replacement can be performed under local anesthesia without opening the chest or stopping the heart.

In this strategy, the device is threaded through the patient's circulatory system via catheter to the aortic valve from either one of two directions.

The antegrade approach involves crossing the patient's septum and mitral valve to reach the native aortic valve. The retrograde approach involves delivering the device directly to the aortic valve through the patient's main artery.

After a delay of nearly six months, the company was given a go-ahead to resume a feasibility trial for its percutaneous aortic heart valve system in December (MDD, Dec. 5, 2005).

The company said it believes the retrograde delivery provides a simpler route for introducing the valve non-surgically than the antegrade approach that was used in its earlier U.S. feasibility trial. The system involves threading the device through the patient's circulatory system from the leg directly to the aortic valve.

The new trial has also incorporated a larger valve size of 26 mm to allow for what the company termed “more optimal sizing” and to treat a broader range of patients.

The three institutions participating in the feasibility study are William Beaumont Hospital (Royal Oak, Michigan), New York-Presbyterian/Columbia University Medical Center (New York) and theCleveland Clinic Foundation (Cleveland).

The company said it is “actively working” with the FDA to finalize the eventual pivotal trial design while continuing to collect follow-up data on the feasibility cohort. Percutaneous heart valve cases also are continuing at multiple clinical sites in Europe and Canada in pursuit of CE mark approval, it added.

Larry Biegelsen, senior analyst, medical devices, for Prudential Equity Group (New York), wrote in a research note that the enrollment of the first 20 patients and the expansion of the study are both positive events for the company.

In particular, he said that the permission to expand the feasibility study can be seen “as a vote of confidence from the FDA because [Edwards] had to show the FDA data from the initial 20 patients.” He noted that new sites may be added to the trial.

Biegelsen also pointed out that the start of the company's pivotal trial is not contingent upon the additional 35 patients, and he estimated that the U.S. pivotal trial could begin in 3Q07 but “may start sooner,” given the positive FDA news.

In late 2004, the company had targeted U.S. approval for the device by 2008-2009, but it has yet to provide an official update to that guidance which will most certainly be extended due to the delay last year.

In an e-mail exchange Rowe told MDD that the company is “working closely with the FDA to determine the next steps in support of a U.S. approval but cannot speculate on an actual PMA timeline at this point.”

He did note, however, that in Europe, the company is continuing to train physicians and add new sites, “which would position us to receive the CE mark by the end of 2007.”

The company reported late last year that it has developed a new approach for placing a Cribier-Edwards valve in a beating heart. The new transapical placement is a procedure in which the valve is delivered through a mini-incision between the ribs using the Ascendra aortic valve replacement system, developed specifically for the new procedure.

The company said the new approach gives it “another access route to implant that valve.” It is believed that the transapical approach would be geared primarily to vascular surgeons, whereas the percutaneous approach would be welcomed by interventional cardiologists.

Edwards has estimated the global non-surgical aortic valve opportunity to be about $300 million in 2010, growing to $800 million in 2014. Rowe noted that the opportunity could exceed $1 billion some time in the next decade.