11.13.13
Medtronic Inc. unveiled the highly anticipated results from the U.S. pivotal trial of its CoreValve catheter-delivered aortic valve device during the recent Transcatheter Cardiovascular Therapeutics (TCT) annual conference in San Francisco, Calif.
As a result, current U.S. market leader, Irvine, Calif.-based Edwards Lifesciences should nervously be looking over its shoulder. U.S. approval of CoreValve could land a serious blow to Edwards’ monopoly of the catheter-delivered aortic valve market.
The U.S. Food and Drug Administration (FDA) has determined it will conduct separate reviews for the trial’s extreme-risk and high-risk studies. Upon reviewing the CoreValve Trial’s results for extreme risk patients, the FDA has determined it has sufficient information to evaluate the safety and efficacy of the Medtronic CoreValve System for this patient group without the need for an external expert panel. Medtronic anticipates receiving FDA approval of CoreValve System for extreme risk patients by the end of fiscal year 2014 (end of April).
The focus then will switch to gaining approval for use in patients who, while not totally unable to undergo surgery, are at high risk for complications. Pivotal one-year data in this cohort will be released at the American College of Cardiology meeting in March (in Washington, D.C.), Medtronic officials say, with U.S. approval occurring around a year from now. This time the FDA unlikely will be willing to waive the advisory committee.
With an overall survival rate of 76 percent for CoreValve at 12 months, compared with 69 percent in the pivotal trial of Edwards’ Sapien valve, and a greater choice of delivery routes, Edwards has reason to be afraid.
The data presented during TCT was the first U.S. data presented on the system. The data met its primary endpoint in patients who were considered too ill or frail to have their aortic valves replaced through traditional open-heart surgery, with a rate of death or major stroke of 25.5 percent at one year. This result is highly significant as it was 40.7 percent lower in patients treated with the CoreValve System than was expected with standard therapy (a pre-specified performance goal of 43 percent). The equivalent rate in the pivotal trial of Sapien was 35 percent.
The rate of stroke—one of the complications most concerning to physicians and patients because it increases mortality and affects quality of life—is among the lowest reported. At one month, the major stroke rate was 2.4 percent, and it remained low over time with a one-year rate of 4.1 percent (compared with Sapien’s 7.8 percent). In addition, in more than 800 extreme risk patients enrolled in the CoreValve Continued Access Study, CoreValve patients experienced an even lower rate of major stroke (1.8 percent at one month).
“The fact that nearly three-quarters of patients were alive and free of strokes at one year is remarkable, given the complex medical conditions and extreme frailty of this population. Not only do the results meet the CoreValve study’s safety and efficacy endpoints for patients at extreme risk for surgery, but the positive clinical outcomes and low complication rates set a high standard for what transcatheter valves can achieve,” said Jeffrey J. Popma, M.D., director of Interventional Cardiology at the Beth Israel Deaconess Medical Center, in Boston, Mass., and co-principal investigator of the trial who presented the results at TCT.
The study also found significant and sustained functional and quality-of-life improvements, with the heart failure symptoms of most patients (90 percent) improving at least one class at one year (as measured by New York Heart Association Class), and quality-of-life scores improving 27.4 points at one year (as measured by the Kansas City Cardiomyopathy Questionnaire 100-point scale, in which a 20-point change is considered highly significant).
Overall hemodynamic (blood flow) performance was strong with mean gradients (resistance) of 8.5 mmHg (millimeters of mercury) at one month and 8.8 mmHg at one year, similar to the gold standard surgical valves. Paravalvular leak (PVL) rates were low and improved over time with only 11.5 percent of patients having more than mild PVL at one month, which improved to only 4.1 percent at one year. Notably, more than 80 percent of patients with moderate PVL at one month had a reduction in the severity of PVL by one year, an improvement that has not been reported in other major transcatheter aortic valve replacement (TAVR) trials.
Furthermore, CoreValve patients with moderate PVL had no greater mortality risk than patients with less PVL.
Major vascular complication rates were low: 8.3 percent at one month and 8.5 percent at one year. Consistent with previous studies on self-expanding technology, the permanent pacemaker rate was 22.2 percent at one month and, importantly, pacemaker implants were not associated with mortality for these patients.
“In the recent past, these patients had no good treatment option and a 50 percent chance of death at one year. Along with the clinical community, we are very encouraged by the results in this rigorously conducted trial and look forward to continuing our effort to bring this transformational therapy to patients with life-threatening aortic valve disease in the United States,” said John Liddicoat, M.D., senior vice president, Medtronic, and president of Medtronic’s Structural Heart Business. “In particular we wish to commend the 40 enrolling sites and their heart teams for their exceptional commitment to patients and for the meticulous conduct of this trial.”
In the study, 471 patients were treated with the CoreValve System, a self-expanding, low 18 Fr profile system with three valve sizes (26 mm, 29 mm, 31 mm) delivered via the femoral artery. Patients were monitored by independent core labs and evaluated against a performance goal developed in partnership with the FDA. In the CoreValve Continued Access Study, 830 extreme risk patients have been treated with CoreValve System.
The downside for Medtronic was the rate of pacemaker implantation—a pacemaker was required in 22.2 percent of patients. The rate with Sapien was around 6 percent. Medtronic was at pains to point out that pacemaker implantation was not associated with decreased survival at one year. Comparing the results from two different trials is tricky and should, of course, be done with caution, but in the absence of a head-to-head trial it is hard to know how better cardiologists can judge the valves’ performance.
The importance of the U.S. market is growing, as the European market becomes more crowded. Boston Scientific’s Lotus aortic valve was granted CE mark on Oct. 28, bringing the total number of transcatheter aortic valves on sale in Europe to seven.
Considering the excellent outcomes transcatheter valves can offer over surgery, uptake of the devices has been slower than expected—probably because they’re really expensive. The devices can cost up to $30,000, far more than surgically implanted valves, even taking the shorter healing times into account.
Their utility in inoperable patients is inarguable, but their cost-effectiveness in high-risk groups has been the subject of some discussion. Glenn Novarro, an analyst at RBC Capital Markets, says that both government and private insurers in the United States strictly limited off-label use of transcatheter valves.
That said, in 2012, the U.S. sales of Edwards’ Sapien valve totaled $238 million and this will rise to $869 million in 2018, according to EvaluateMedTech’s consensus forecasts. CoreValve’s U.S. sales are predicted to grow faster, with $570 million worth of business expected in 2018. Cost-effectiveness in today’s evolving healthcare model, clearly is the name of the game, but there still is money to be made, analysts predict.
Approximately 300,000 people worldwide suffer from severe aortic stenosis, including one-third who are ineligible for open-heart surgery because they are deemed too high risk. Since receiving CE mark in 2007, the CoreValve System has been implanted in more than 45,000 patients in more than 60 countries.
As a result, current U.S. market leader, Irvine, Calif.-based Edwards Lifesciences should nervously be looking over its shoulder. U.S. approval of CoreValve could land a serious blow to Edwards’ monopoly of the catheter-delivered aortic valve market.
The U.S. Food and Drug Administration (FDA) has determined it will conduct separate reviews for the trial’s extreme-risk and high-risk studies. Upon reviewing the CoreValve Trial’s results for extreme risk patients, the FDA has determined it has sufficient information to evaluate the safety and efficacy of the Medtronic CoreValve System for this patient group without the need for an external expert panel. Medtronic anticipates receiving FDA approval of CoreValve System for extreme risk patients by the end of fiscal year 2014 (end of April).
The focus then will switch to gaining approval for use in patients who, while not totally unable to undergo surgery, are at high risk for complications. Pivotal one-year data in this cohort will be released at the American College of Cardiology meeting in March (in Washington, D.C.), Medtronic officials say, with U.S. approval occurring around a year from now. This time the FDA unlikely will be willing to waive the advisory committee.
With an overall survival rate of 76 percent for CoreValve at 12 months, compared with 69 percent in the pivotal trial of Edwards’ Sapien valve, and a greater choice of delivery routes, Edwards has reason to be afraid.
The data presented during TCT was the first U.S. data presented on the system. The data met its primary endpoint in patients who were considered too ill or frail to have their aortic valves replaced through traditional open-heart surgery, with a rate of death or major stroke of 25.5 percent at one year. This result is highly significant as it was 40.7 percent lower in patients treated with the CoreValve System than was expected with standard therapy (a pre-specified performance goal of 43 percent). The equivalent rate in the pivotal trial of Sapien was 35 percent.
The rate of stroke—one of the complications most concerning to physicians and patients because it increases mortality and affects quality of life—is among the lowest reported. At one month, the major stroke rate was 2.4 percent, and it remained low over time with a one-year rate of 4.1 percent (compared with Sapien’s 7.8 percent). In addition, in more than 800 extreme risk patients enrolled in the CoreValve Continued Access Study, CoreValve patients experienced an even lower rate of major stroke (1.8 percent at one month).
“The fact that nearly three-quarters of patients were alive and free of strokes at one year is remarkable, given the complex medical conditions and extreme frailty of this population. Not only do the results meet the CoreValve study’s safety and efficacy endpoints for patients at extreme risk for surgery, but the positive clinical outcomes and low complication rates set a high standard for what transcatheter valves can achieve,” said Jeffrey J. Popma, M.D., director of Interventional Cardiology at the Beth Israel Deaconess Medical Center, in Boston, Mass., and co-principal investigator of the trial who presented the results at TCT.
The study also found significant and sustained functional and quality-of-life improvements, with the heart failure symptoms of most patients (90 percent) improving at least one class at one year (as measured by New York Heart Association Class), and quality-of-life scores improving 27.4 points at one year (as measured by the Kansas City Cardiomyopathy Questionnaire 100-point scale, in which a 20-point change is considered highly significant).
Overall hemodynamic (blood flow) performance was strong with mean gradients (resistance) of 8.5 mmHg (millimeters of mercury) at one month and 8.8 mmHg at one year, similar to the gold standard surgical valves. Paravalvular leak (PVL) rates were low and improved over time with only 11.5 percent of patients having more than mild PVL at one month, which improved to only 4.1 percent at one year. Notably, more than 80 percent of patients with moderate PVL at one month had a reduction in the severity of PVL by one year, an improvement that has not been reported in other major transcatheter aortic valve replacement (TAVR) trials.
Furthermore, CoreValve patients with moderate PVL had no greater mortality risk than patients with less PVL.
Major vascular complication rates were low: 8.3 percent at one month and 8.5 percent at one year. Consistent with previous studies on self-expanding technology, the permanent pacemaker rate was 22.2 percent at one month and, importantly, pacemaker implants were not associated with mortality for these patients.
“In the recent past, these patients had no good treatment option and a 50 percent chance of death at one year. Along with the clinical community, we are very encouraged by the results in this rigorously conducted trial and look forward to continuing our effort to bring this transformational therapy to patients with life-threatening aortic valve disease in the United States,” said John Liddicoat, M.D., senior vice president, Medtronic, and president of Medtronic’s Structural Heart Business. “In particular we wish to commend the 40 enrolling sites and their heart teams for their exceptional commitment to patients and for the meticulous conduct of this trial.”
In the study, 471 patients were treated with the CoreValve System, a self-expanding, low 18 Fr profile system with three valve sizes (26 mm, 29 mm, 31 mm) delivered via the femoral artery. Patients were monitored by independent core labs and evaluated against a performance goal developed in partnership with the FDA. In the CoreValve Continued Access Study, 830 extreme risk patients have been treated with CoreValve System.
The downside for Medtronic was the rate of pacemaker implantation—a pacemaker was required in 22.2 percent of patients. The rate with Sapien was around 6 percent. Medtronic was at pains to point out that pacemaker implantation was not associated with decreased survival at one year. Comparing the results from two different trials is tricky and should, of course, be done with caution, but in the absence of a head-to-head trial it is hard to know how better cardiologists can judge the valves’ performance.
The importance of the U.S. market is growing, as the European market becomes more crowded. Boston Scientific’s Lotus aortic valve was granted CE mark on Oct. 28, bringing the total number of transcatheter aortic valves on sale in Europe to seven.
Considering the excellent outcomes transcatheter valves can offer over surgery, uptake of the devices has been slower than expected—probably because they’re really expensive. The devices can cost up to $30,000, far more than surgically implanted valves, even taking the shorter healing times into account.
Their utility in inoperable patients is inarguable, but their cost-effectiveness in high-risk groups has been the subject of some discussion. Glenn Novarro, an analyst at RBC Capital Markets, says that both government and private insurers in the United States strictly limited off-label use of transcatheter valves.
That said, in 2012, the U.S. sales of Edwards’ Sapien valve totaled $238 million and this will rise to $869 million in 2018, according to EvaluateMedTech’s consensus forecasts. CoreValve’s U.S. sales are predicted to grow faster, with $570 million worth of business expected in 2018. Cost-effectiveness in today’s evolving healthcare model, clearly is the name of the game, but there still is money to be made, analysts predict.
Approximately 300,000 people worldwide suffer from severe aortic stenosis, including one-third who are ineligible for open-heart surgery because they are deemed too high risk. Since receiving CE mark in 2007, the CoreValve System has been implanted in more than 45,000 patients in more than 60 countries.