By: Jeffrey Shuren, M.D., J.D.
At FDA’s medical devices center, we have a vision—it’s what we strive for each day in our review and assessment of new medical technology. And patients are at the very core of that vision: “Patients in the U.S. have access to high-quality, safe, and effective medical devices of public health importance first in the world.”
Our actions are focused on improving the health and enhancing the quality of life of patients. If a device is safe and effective, we want patients to have access to it as quickly as possible—especially if the patients suffering have little to no treatment options.
This week, we’ve taken steps to help those patients suffering from heart valve disease, which impacts more than 5 million Americans, many of whom have few treatment options and are fighting to survive.
Aortic valve stenosis is a serious, progressive, age-related disease that is commonly caused by calcium deposits on the aortic valve that cause it to narrow.. As the heart works harder to pump blood through the smaller opening, it can eventually weaken. Aortic valve stenosis can lead to fainting, chest pain, heart failure, irregular heart rhythms (arrhythmias), or cardiac arrest.
Of those 5 million Americans, 1.5 million suffer from aortic valve stenosis and some 500,000 of those have severe aortic stenosis. Patients with severe aortic stenosis will most likely need open-heart surgery to replace their aortic valve. Without such a replacement, progressive heart failure may result and 50 percent of patients may not survive more than an average of two years after the onset of their symptoms.
Until recently, aortic valve replacement required an open-heart surgical procedure, which involves accessing the heart through an incision between the ribs or through the breastbone, while the patient is supported by a heart-lung machine. Unfortunately, many of these patients are elderly and have additional conditions, such as extreme frailty or liver disease. This makes the surgical procedure either too risky to attempt (inoperable) or very risky for death and permanent complications (high-risk for surgery).
In the past few days, FDA has expanded patient access to the benefits of aortic valve replacement by approving the use of two transcatheter heart valve (THV) systems. These catheter-based therapies provide the only effective therapy for inoperable patients and are alternatives to open-heart surgery for patients at high risk for surgery. Both systems allow physicians to perform aortic valve replacement using catheters, so patients benefit from reduced symptoms of heart failure and improve their chances for survival.
Both THVs are typically implanted through an artery in the leg, without opening the chest or heart, or removing the diseased valve. The replacement valve is compressed into a thin, flexible tube called a delivery catheter. The delivery catheter and the replacement valve are inserted into the femoral artery and pushed up to the diseased valve. The replacement valve is then released from the delivery catheter to become immediately functional. If the femoral arteries are not suitable, the replacement valve can be directly inserted into the tip of the heart, other arteries, or the aorta itself, without using the heart-lung machine.
On June 12, 2014, FDA expanded the use of the CoreValve, a self-expanding THV manufactured by Medtronic, to include patients who are at high-risk for open-heart surgery. We had previously approved CoreValve only for inoperable patients. FDA based its approval of CoreValve on clinical data from a 795-patient randomized, clinical study conducted in the United States, comparing the safety and effectiveness of transcatheter aortic valve replacement using CoreValve with that of surgery in patients at high-risk for open-heart surgery. This study showed a lower mortality rate for patients treated with CoreValve.
And today, June 16, FDA approved the Sapien XT, a balloon-expandableTHV, manufactured by Edwards Lifesciences. The Sapien XT is a revised version of their earlier Sapien THV for use in patients with aortic valve stenosis who are either inoperable or at high-risk for open-heart surgery.
The Sapien XT THV uses a smaller profile delivery system than the previously approved Sapien THV. The smaller system helps patients with small or severely diseased vessels. The Sapien XT is also available with an additional, larger-size 29-mm valve, which helps patients with larger-size native aortic valves.
For the Sapien XT approval, FDA based its decision on clinical data from a randomized clinical study and several, single-arm nested registries, conducted in the U.S. The 560-subject randomized clinical trial showed that, for inoperable patients, the Sapien XT device was as safe and effective as the previously approved Sapien device, with better procedure outcomes and reduced vascular complication rates.
The agency also reviewed clinical data from the European SOURCE XT Registry, Society of Thoracic Surgeons /American College of Cardiology Transcatheter Valve Therapy (TVT) Registry, and peer-reviewed articles that showed the benefits of the Sapien XT device for high-risk patients outweighed the risks of the device.
We approved the Sapien XT THV despite observing certain quality system violations during a recent inspection at the Edwards manufacturing facility where the Sapien XT delivery systems and accessories are made. Quality system requirements govern the design, manufacture, and distribution of devices, and we conduct such inspections to assure that devices are safe and effective. When violations occur, according to federal law, we cannot approve a company’s medical device—unless, we allow deviation from quality system requirements through what is known as a “variance.”
This is a rarely used regulatory action that is employed only in special situations of public health need. FDA may grant a variance from any device quality system requirement when the agency determines that it is in the best interest of the public health and that the firm seeking the variance has alternate methods and controls in place sufficient to assure that the device will be safe and effective and otherwise in compliance with the Act.
We granted Edwards Lifesciences a variance from the quality systems requirements for two reasons.
First, we determined that there is an important, immediate need for these technology options and that Sapien XT demonstrates a reasonable assurance of safety and effectiveness for its intended use. This means patients who really need this technology could and should receive it.
And second, Edwards Lifesciences presented us with an appropriate variance plan for addressing its manufacturing problems—including specific controls to permit safe use of the Sapien XT while corrections are underway.
We are committed to flexible, smart regulation, and to working with companies and the clinical community to ensure that innovative new medical devices that demonstrate a reasonable assurance of safety and effectiveness are available for patients in a timely manner.
There is a clear and important public health need for both these devices. With the additional availability of two THV systems, physicians will now be able to treat the widest possible spectrum of patients with severe and symptomatic aortic stenosis. They will be able to choose the procedure or device that best suits each individual patient based on unique patient characteristics, anatomic constraints, implant procedure risks, device characteristics, and overall benefit-risk profiles.
After all, patients are at the core of what we do.
Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health