A New, Non-Surgical Percutaneous Treatment Alternative for Mitral Regurgitation
The MitraClip system is a novel first-in-class technology, which has shown promise under an investigational device exemption (IDE) phase I feasibility study (EVEREST I) and is now in a phase II pivotal study (EVEREST II). The percutaneous MitraClip procedure is a new non-surgical treatment alternative for patients who suffer from a condition known as mitral regurgitation (MR) where the mitral valve does not close properly, allowing blood to flow backward into the left atrium, decreasing blood flow to the body. MR is the most common type of heart valve insufficiency in the US; it™s the econd most common type of heart valve disease in Europe. It affects millions of people worldwide. A significant issue for patients with MR is that the vast majority are left untreated, leaving their hearts affected by the leak, causing chronic volume overload. This requires the heart to work harder, often leading to heart failure. Many of these patients go untreated because of the significant risks and trauma associated with current open arrested- heart surgery.
On an annual basis in the US alone, there are approximately 250,000 new patients with significant MR diagnosed. Currently, only 20% of these patients are estimated to undergo surgery. MR is an under-treated condition that is often associated with heart failure.
Evalve estimates that approximately two-thirds of the patients who are diagnosed annually with significant MR could potentially benefit from treatment with the MitraClip device. The early data has indicated that patients™ options for mitral valve surgery are preserved after an unsuccessful clip procedure.
Using the MitraClip System
The MitraClip device enables the clinician to repair a patient™s leaky mitral valve using a catheter-based system. Evalve believes this minimally invasive approach will reduce the risks, trauma, and costs associated with open arrested-heart surgical options. The EVEREST II study is radomizing patients to either the MitraClip device or surgery to evaluate the assumption that the percutaneous clip procedure will provide clinical benefits similar to those from surgery.
Additionally, investigators have completed enrollment in an arm of the EVEREST II study for high-risk surgical patients. Initial data indicate that the itraClip procedure may also be a good alternative for patients who are not able to undergo the trauma associated with open-heart surgery├óÔé¼ÔÇØand as a result currently remain untreated.
Mechanical Solution for a Mechanical Problem
Evalve transformed an existing open-chest arrested-heart surgical procedure, known as the Alfieri technique (edge-to-edge mitral valve repair), into the percutaneous catheter-based procedure. With the Alfieri technique, the surgeon sutures the leaflets together at the point of the leak in the valve. By doing this, closure of the valve is facilitated, which reduces MR. The valve continues to open and close on either side of the sutures, allowing normal forward blood flow.
The MitraClip device mimics the Alfieri technique although much less invasively using a catheter system that is inserted into the femoral vein. The MitraClip device, located at the end of the delivery catheter, is used to grasp the leaflets of the mitral valve while the heart is fully functional and beating. Once the clip is attached to the leaflets, the clinician is able to assess real-time whether the reduction in regurgitation is adequate. If the physician is not satisfied with the result, the clip can be repositioned to improve the result. This step of the procedure can be repeated until the physician is satisfied with the final result, at which time the clip is deployed on the leaflets.
Moving Toward Commercialization
Evalve obtained CE Mark approval for the MitraClip system in March 2008, and is now establishing a sales organization and training programs needed to start sales in Europe. In North America, Evalve is continuing the phase II pivotal study and expects to complete enrollment in that study by the end of 2008. Allowing time for the required patient follow- p, analysis of the data, and the Food and Drug Association (FDA) review process, Evalve is currently expecting commercial approval in the US by he end of 2010.
Evalve has invested significant resources to train both interventional cardiologists and echocardiologists. Training includes time on-site with the physicians reviewing the MitraClip system and the important echocardiographic images used during the procedure.
Evalve is the only company that has initiated and completed more than 80% of enrollment in a phase II pivotal study of percutaneous mitral repair. In addition, Evalve is the only company that has successfully completed a feasibility study in the US and received CE Mark approval for a percutaneous mitral repair system.
EVEREST Study Overview
Investigators have now treated more than 325 patients with more than 400 clips implanted in the EVEREST studies in the US and Canada. The EVEREST II study is a randomized, controlled, multicenter clinical trial evaluating the safety and efficacy of the MitraClip system in patients with moderate-to-severe or severe MR, compared with surgical repair or replacement. The primary effectiveness endpoint is freedom from surgery for valve dysfunction, death, and moderate-to-severe (3+) or severe (4+) MR at 12 months. The primary safety end-point is freedom from major adverse events at 30 days or hospital discharge whichever is longer. The national co-principal investigators are Ted Feldman, Director of the Cardiac Catheterization Lab at Evanston Northwestern Healthcare, and Don Glower, Professor of Surgery at Duke University An initial cohort of 107 non-randomized patients treated in the two EVEREST studies shows that the MitraClip device can be successfully implanted in a majority of patients. Investigators chose to implant the clip in more than 90% of these cases, of which approximately 75% achieved a reduction in MR to a level that is no longer clinically significant (2+ MR). Patients have been remarkably stable throughout the procedure, and a low complication rate was reported for this cohort. After the MitraClip procedure, patients were usually discharged home in two days without nursing care. These rates of hospital stay and lack of need for nursing care differ greatly from open arrested-heart surgery, where patients are in the hospital for five to seven days on average, with approximately 40% of valve surgery patients requiring nursing care after discharge from the hospital.
A New Alternative for a Serious Condition
Although many people have not heard of MR specifically, approximately50% of patients who suffer from heart failure in the US have significant MR. Sometimes heart failure causes MR, but more often MR is the cause of heart failure. Either way, MR results in a progressive worsening of heart failure. Treating MR in these patients may reduce the symptoms of heart failure, and, just as importantly, improve the quality of life for these patients. Since heart failure is a progressive disease, patients are frequently in and out of the hospital to treat their disease. A reduction in their MR may improve their clinical status and reduce the need for hospitalization. Successfully treating these patients may also have a positive economic impact on the healthcare system.
Early clinical data in a subset of the initial non-randomized patient cohort n=54, matched data) shows that when MR is successfully reduced with the MitraClip device, heart failure symptoms improve as measured by the New York Heart Association functional class. Specifically, 75% of the patients improved by at least one class or more.
Recently published data in the New England Journal of Medicine├óÔé¼ÔÇØ from the Mayo Clinic and in Circulation├óÔé¼ÔÇØby Dr Rosenhek from Europe shows that the majority of patients with severe MR, even when initially asymptomatic, progress to heart failure, die, or need surgery.
Evalve anticipates that the MitraClip device will be available commercially in the US and Canada by the end of 2010 to provide a less invasive, potentially safer treatment alternative to surgical treatment for MR.
More information about MR and EVEREST II can be found at www.mitralregurgitation.org "