From the March 26, 2007, issue of "The Gray Sheet"
Edwards Lifesciences will soon begin a 600-patient U.S. pivotal clinical trial for its Sapien transcatheter aortic replacement heart valve at Columbia University Medical Center and the Cleveland Clinic, the company says.
Announced March 20, FDA clearance allows the company to enroll the first 40 patients at up to eight centers in the PARTNER trial (Placement of AoRTic traNscathetER valves). Edwards plans to expand the trial to 15 additional sites, pending FDA clearance.
According to Edwards, FDA will likely allow the planned expansion after it reviews additional follow-up data from the 55-patient, nonrandomized Sapien feasibility trial, which the company plans to submit next month. Edwards also will submit to FDA data from Canadian and European Sapien patients.
The 30-day mortality rate for Sapien patients in the U.S. feasibility trial was 7.4%. Based on the patients' risk factors, researchers estimate that without Sapien, about a third would have died within 30 days, according to Edwards.
The PARTNER study will assign patients to one of two separate, but simultaneous, randomized comparison arms.
In one arm, 350 high-risk patients with severe aortic valve stenosis who are eligible for surgery will be randomized to either conventional open-heart valve surgery or minimally invasive implantation of Sapien.
The other trial arm will randomize 250 patients considered to be too high risk for surgery to either standard medical management or Sapien treatment.
One-year mortality will be the primary endpoint for PARTNER, although FDA had earlier suggested the potential need for two-year data. The two-arm study is designed to show that Sapien is noninferior to open-heart valve surgery and superior to medical management. Secondary endpoints include quality of life and various valve performance measures.
"The goal of the trial is that we can treat all of the patients that are deemed high-risk for traditional open heart surgery and then direct them to what would be optimal therapy for them so they can go to the optimal control group [or get a Sapien]," Edwards VP & General Manager-Transcatheter Replacement Larry Wood told "The Gray Sheet." Those enrolled in the study will be "high-risk patients that we don't believe are well-served by traditional open-heart surgery."
Edwards predicts Sapien will be the first percutaneously delivered heart valve available in the United States following FDA approval in 2010. The company expects it to be ready for commercialization in Europe by the end of 2007.
Aortic stenosis is the narrowing or obstruction of the aortic valve, usually due to calcification or an inherent structural defect. The "gold standard" therapy is open heart valve replacement surgery, which is historically associated with a 30-day mortality rate of around 4%, according to Edwards.
However, the extremely invasive procedure, which requires a sternotomy and heart-lung bypass, is too risky for some patients, especially elderly patients with multiple co-morbidities.
"Our belief is that for every patient that gets traditional open-heart surgery for having a valve replaced, there's another patient out there that could potentially benefit that doesn't get treated, and for a lot of those, it's just because they have too many co-morbidities," Wood said. "This is truly a market-expanding opportunity."
Like Edwards' Perimount surgical replacement heart valves, Sapien is made of bovine tissue mounted on a stainless steel frame and treated with Edward's proprietary ThermaFix anti-calcification process.
Sapien can be delivered on either the RetroFlex transfemoral delivery system through an incision in the leg or the Ascendra transapical delivery system through an incision in the chest for patients whose vasculature is not amenable to the femoral approach. Initially, PARTNER will only include RetroFlex, but Edwards expects to offer the Ascendra option in the trial by the third quarter.
Edwards is the market leader in surgical heart valves, and "the great thing about ... evolving this technology is that we don't have to direct patients to one specific therapy," Wood said. Availability of the percutaneous valve has the potential to increase patient referrals for valve treatment generally, even though the implanting physician might ultimately choose a surgical implant instead, the exec concluded.
- Reed Miller
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