Medical Device Daily Associate

Cardiovascular device maker Edwards Lifesciences (Irvine, California) yesterday said that it is suspending a clinical trial for a minimally invasive procedure to replace the aortic valve after it received reports of complications, including death, among some of the roughly 10 patients enrolled in its U.S. clinical trial.

The company said it is delaying enrollment in its Cribier-Edwards percutaneous aortic heart valve clinical feasibility trials in the U.S. in order to incorporate a new delivery system being evaluated in Canada.

Edwards – which has notified the FDA of the trial postponement – said it took this voluntary action 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 are being performed with a new “retrograde” delivery system. Edwards said that data presented at the 2005 EuroPCR conference in May indicated that the company’s custom retrograde delivery system resulted in positive clinical outcomes in the Canadian trial.

The Cribier-Edwards device 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.

During a conference call on the trial postponement, Michael Mussallem, president and CEO of Edwards, said that the retrograde delivery system results have been shown, so far, to resolve many of the procedural problems associated with the more challenging antegrade approach.

“Based on these favorable results, we have applied to the FDA to incorporate our retrograde system into the feasibility trial and make this option available to patients before resuming enrollment,” Mussallem said. He said the company would apply to add the new system to the trial via an IDE supplement and that it hopes to resume the trial “later this year.”

Stanton Rowe, Edwards’ corporate vice president, Percutaneous Valve Interventions (PVT; Fort Lee, New Jersey), said during the call that thus far all the U.S. cases, as well as the majority of the cases performed in Europe, have involved the antegrade approach. While he said the results have been more challenging with the antegrade approach, he called those results still “encouraging.”

He also noted that Alain Cribier MD, chief of cardiology at University Hospital (Rouen, France), for which the device was named, reported positive results at the EuroPCR conference using the antegrade approach in the RECAST trial comprised of 21 patients.

Even with positive data using the antegrade, Rowe acknowledged that the retrograde approach has produced more favorable clinical success rates and fewer complications and “we expect it to become the preferred method for delivering the percutaneous valve.”

Barry Liden, director of global communications for Edwards told Medical Device Daily that the new retrograde tip catheter was developed in-house. “We tried it out in this new trial in Canada and it seems to be working quite well, making the delivery of the percutaneous valve much easier,” he said.

Interestingly, Liden noted that when the company acquired PVT in January 2004, the antegrade was the predominant approach being used because there were some challenges to the retrograde approach, hence the use of that approach in the European and U.S. trials.

“[At that time], there wasn’t anything made specifically custom-designed for a retrograde going over the aortic arch to access an aortic valve,” he said.

Based on the company’s prior experience with its now discontinued AAA program, company engineers were able to develop the new catheter; however, this work didn’t happen until after the company had already begun its U.S. trials using the antegrade approach, and “our IDE did not specify the use of this [new] delivery catheter,” Liden said.

Rowe said that resumption of the U.S. trial before year’s end almost certainly alters the company’s plans for completing the initial feasibility phase by the end of 2005. However, he declined to give a revised timeline. “It’s premature to estimate how much this delay might impact the timing of our U.S. commercialization,” he said.

In Europe, where the company currently has three clinical sites open, it will postpone adding additional sites while waiting for approval to add the retrograde approach. Rowe predicted a three- to six-month delay in the device’s CE mark approval, thus pushing it into the first half of 2007.

Based on trial postponement, Jason Mills, medical technology analyst for First Albany Capital (San Francisco), expressed skepticism that the company could get U.S. approval for the device by the 2008-2009 target that it had projected in late 2004.

In a research report, he said that his firm agrees with the company’s estimate that the percutaneous valve replacement market is an opportunity that could reach nearly $1 billion in sales by 2010, but suggested that “an FDA approval may not occur until the next decade.”

The company said it does not expect the trial postponement will have a material financial impact. Edwards said it is comfortable with the average analyst estimate for 2Q05 and reiterated its EPS guidance of between $1.90 to $1.95 for the full year.

“We remain confident about the potential of percutaneous heart valve therapies, which offer hope to thousands of patients worldwide who are not good candidates for conventional open-heart valve replacement surgery and face limited options,” Rowe said. “At the same time, this is breakthrough medical therapy, and we want to ensure that we provide this technology in a responsible way to patients suffering from debilitating aortic valve stenosis.”