Medical Device Daily Executive Editor

Playing the percentages.

It's pretty easy to chance 100 bucks or so at the roulette wheel. But not so easy when an elderly patient needs valve repair but surgery offers significant risks: a range of morbidities and rather large possibility of death.

The FDA earlier this year gave Evalve (Menlo Park, California) the go-ahead to expand to a higher-risk surgical group the use of its MitraClip product for percutaneous repair of mitral regurgitation (MR). This is being done via approval of a 70-patient, single-arm registry of these high-risk patients, in addition to the company's ongoing randomized Endovasulcar Valve Edge-to-edge REpair STudy (EVEREST) of the Mitraclip which involves only a low-risk surgical candidates.

Ferolyn Powell, president/CEO of Evalve, told Medical Device Daily that selecting the patients for the registry will be based on a determination of operative mortality risk for each patient's condition, not just guesswork.

She said the company worked with the FDA collaboratively, making the decision to use a risk calculator, developed by the Society of Thoracic Surgeons (Chicago) which will include those patients at risk for operative mortality — in the surgical procedure — at 12% or greater. The hope, of course, is that treatment with the Mitraclip will prove to be much lower risk.

"You enter the patient's co-morbidities into this calculator, which then calculates the patient's operative mortality risk to determine if they can qualify for this higher-risk study," Powell said. "They are not randomized; if they meet inclusion criteria they go directly to the Mitraclip treatment."

She added: "It's not a historical control — it's based on the calculation [of mortality risk] for the patients that are treated in this study."

Evalve's Percutaneous Mitral Repair for MR is performed in the cath laboratory. The heart beats normally during the procedure, therefore not requiring a heart-lung bypass machine. The percutaneous approach means less invasiveness, less blood loss, faster recovery.

Powell reported that six procedures have been performed in the high-risk registry thus far.

Powell said she believes that the FDA sees the registry as providing data for the Mitraclip procedure for higher-risk patients.

"This is a very important group of patients that have no other good options [for treatment]. Clinicians need to understand what this technology offers to these patients," she said.

Thus, she described the registry as "a potential way to treat more higher-risk people who suffer from mitral regurgitation and to gather more valuable scientific data for clinicians and their patients."

The FDA, "clearly required a randomized, controlled trial for approval, but it was difficult to randomize a high-risk population" — thus providing the best rationale for the single-arm registry approach.

She added that the registry — "absolutely" — will be included with the data being collected via EVEREST.

"It will," she said, citing market interests as well as therapeutic decision-making.

"We expect that when the product is introduced to market, the most rapid adoption will be for treatment of these higher-risk patients."

The ongoing randomized study arm of EVEREST II compares the safety and efficacy of the MitraClip device to open arrested heart surgery at more than 40 sites in the U.S. and Canada. Patients are randomized 2:1 to receive the MitraClip device or standard mitral valve surgery.

Evalve reports that more than 160 patients have been treated with a MitraClip device in EVEREST.

"We're working hard to complete both the randomized trail and the registry arm early in 2008," Powell said. The randomized group will then be followed for 12 months to early 2009, followed by PMA submission and hoped-for approval of the Mitraclip in early 2010, she said.

She said the company has also set its sights on obtaining CE-marking by the end of this year.

An estimated four million people in the U.S. have significant (classed as 3+ or 4+) MR, with an annual incidence of 250,000 newly diagnosed patients. However, only 20% of these patients, or about 50,000, undergo surgery each year; the other 200,000 — including the higher-risk population — receive palliative medical therapy.

Thus, the new registry is getting strong endorsement from physicians.

Patrick Whitlow, MD, director of interventional cardiology, is EVEREST II Principal Investigator at Cleveland Clinic (Cleveland), and Ted Feldman, MD, director of the cardiac catheterization lab at Evanston Hospital (Evanston, Illinois), is EVEREST II National Principal Investigator.

Feldman said, "Many MR patients do not undergo surgery because they have other conditions that put them at significant risk for operative mortality and morbidity. Many of these higher-risk patients have been referred to the EVEREST study, but until now were not eligible to participate."

"Less invasive options are important for the higher-risk patients," said Nicholas Smedira, M.D., Director for the Kaufman Center for Heart Failure, Cardiac Transplantation and Mechanical Circulatory Support at Cleveland Clinic. "Patients not only do better during non-invasive procedures, but they tend to recover quicker."

At the Transcatheter Cardiovascular Therapeutics meeting in October, investigators presented data on the first 92 non-randomized patients in EVEREST, with completed 30-day follow-up and echocardiographic lab analysis. The results showed significant reduction of MR in patients with the two most common types of MR: degenerative and functional (MDD, Oct. 26, 2007).

The data also showed that 73% of patients avoided mitral valve surgery and improved procedural success rates, including a 90% success rate in the last 30 procedures reported; and a 95% freedom from major adverse events at 30 days.

"Based on promising data to date, particularly with respect to safety, the MitraClip device may be a viable treatment option for these higher-risk patients," said Donald Glower, MD, professor of cardiovascular surgery, Duke University Medical Center (Durham, North Carolina), and co-principal Investigator of EVEREST II.

Powell reported that Evalve has raised $57 million to date, and she said that the company is "in the process" of developing another round of $40 million.

"These funds are planned to be used to take us through the PMA process," she said, with additional funding required for production and sales ramp-ups following approval.

Powell noted that Evalve, along with several other companies, were launched over the last seven years, all working on percutaneous mitral valve repair technologies. And she isn't hesitant about putting the company in the forefront of this particular race.

"We're currently the only percutaneous mitral valve repair company that's completed a feasibility study in the U.S., and that is now enrolling a pivotal study."