Christopher Delporte, Editorial Director06.10.14
You say puh-tay-toe; I say puh-tah-toe. TAVR or TAVI? Give or take a consonant, they’re the same thing. Transcatheter aortic valve replacement (or implantation) is a minimally invasive surgical procedure that replaces the aortic valve of the heart through the blood vessels as opposed to valve replacement via traditional open-heart surgery. The market has been dominated by two companies, with others hustling to vie for position. As the technology grows in acceptance (clinically as well as from regulatory and reimbursement perspectives), cardiovascular firms are working on newer versions and indications for the tiny, intricate devices. No matter how you spell it, companies are reading large market opportunity.
The Clinical Case
The aortic valve is located between the pumping chamber on the left side of the heart and the aorta, which is a major artery. The aorta carries oxygen-rich blood from the heart to the rest of the body. The valve should be closed while the heart is filling with blood. When the heart chamber squeezes to push blood into the aorta, the valve should open fully to allow blood flow.
Sometimes, particularly as we age, aortic stenosis—a narrowing of the aortic valve—can occur. This leads to increased stress and pressure on the heart muscle, which initially can result in chest discomfort or pain, shortness of breath, leg swelling, fatigue or fainting. Left untreated, the heart muscle can weaken over time resulting in worsening of symptoms and death. The most common cause of aortic stenosis is degenerative—age-related calcium deposits.
Aortic stenosis is the third most prevalent form of cardiovascular disease in the Western world after hypertension and coronary artery disease. Considered a potentially life-threatening condition, the aortic heart valve becomes calcified and does not open properly. Roughly 25 percent of people 65 and older have aortic valve thickening and 3 percent age 75 and older have severe stenosis.
Somewhat similar to a stent placed in an artery, the replacement aortic valve is delivered via catheter through several access methods. With TAVR, a fully collapsible (compressed down to the width of a pencil) replacement is moved to the natural valve site through a catheter primarily through one of two approaches: entering through the vein in the groin (called a transfemoral approach) or from between two ribs through the wall of the heart (called a transapical approach). Other delivery methods in today’s practice include subclavian (beneath the collar bone) and direct aortic (through a minimally invasive surgical incision into the aorta). Placement of the valve happens while the heart is still beating.
Once the new valve is put into place, it is expanded to push the old valve’s leaflets (the human aortic valve has three leaflets—delicate flaps—that stop blood flowing back into the left ventricle of the heart) out of the way and the tissue in the replacement valve takes over the job of regulating blood flow. The goal also is to prevent aortic regurgitation, a condition that occurs when the aortic valve doesn’t close tightly. Aortic valve regurgitation allows some of the blood that was just pumped out of the left ventricle to leak back into it.
Prior to the introduction of the TAVR option, surgeons had one primary path available to them—an open-heart procedure with a sternotomy in which an incision is made, the chest is cracked apart, the patient is placed on a heart-lung machine (stopping the heart), and the heart is opened to insert a new valve. Though it may sound positively barbaric compared to TAVR, it is still the most common method to replace a diseased valve for patients healthy enough for the procedure. Other options to treat valve narrowing include medication for the symptoms (though they don’t stop the progression of the disease) or balloon aortic valvuloplasty, in which a balloon is inserted into the aortic valve through a catheter that temporarily enlarges the valve opening but is temporary.
At present in the United States, TAVR primarily is only indicated for high-risk patients who are considered too frail to undergo open-heart surgery—but experts expect that indication to broaden as time goes on, additional studies are conducted, new device iterations are introduced, and safety of the procedure and technology are proven in the longer-term.
The benefits of the less-invasive procedure are that it’s much less traumatic for the body and, in most cases, it means a faster recovery time. A TAVR procedure, experts caution, is not without risks, but it provides a beneficial treatment alternative to people who just a few years ago may have had limited treatment options.
Market Leaders
The two 800-pound gorillas in the TAVR market at the moment are Edwards Lifesciences Inc. and Medtronic Inc. Though Edwards was first to market in the United States, Medtronic has been working to make up ground, and the two heavyweights have duked it out in what many analysts predict is a $3 billion global TAVR marketplace. The firms also have taken their battle to courtrooms internationally.
Edwards launched its Sapien valve in the European market in 2007. Approval by the U.S. Food and Drug Administration (FDA) came in 2011 for implantation using the transfemoral route. In 2012, the agency approved widened approval to those eligible for surgery (though still high risk) and use of the transapical route of entry. Sapien is a balloon-expanded device built on a stainless steel frame, and the three leaflets are made from tissue found in the outer wall of the cow heart (bovine pericardium).
Medtronic’s CoreValve device also was given CE mark in 2007, but Edwards didn’t have any competition in the U.S. market until January of this year when CoreValve received FDA approval. Like Sapien, CoreValve was approved for patients too frail to undergo traditional open-heart valve replacement. Notably, the Medtronic device was given the green light by the agency without the input of an independent device advisory panel, which usually is customary. In late 2013, the FDA announced it would not require an advisory committee to weigh in on whether the data supported approval, noting that data from the extreme-risk cohort of Medtronic’s clinical trial would be sufficient. CoreValve, which is a self-expanding device made of a nickel-titanium frame with a tri-leaflet valve created from porcine pericardium (derived from pig heart tissue), can be implanted via the femoral artery, subclavian or by direct aortic access. Medtronic anticipates FDA approval of the CoreValve System for high-risk patients sometime this summer.
Sapien and CoreValve come in a range of sizes, and both have had extremely solid clinical results.
Data presented at this year’s American College of Cardiology (ACC) annual meeting and simultaneously published in the New England Journal of Medicine showed that patient results with CoreValve system were superior to surgical aortic valve replacement at one year in patients at increased risk for surgery. It was the first time a prospective, randomized study has shown any transcatheter aortic valve to be superior to surgery. Upon reviewing the CoreValve Trial’s results for high-risk patients, the FDA 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. Thus is the rational behind Medtronic’s anticipation of FDA approval of the CoreValve System for high-risk patients this summer.
Following the ACC meeting, analysts were bullish on Medtronic’s prospects.
Joanne Wuensch, an analyst with BMO Capital Markets told Medical Product Outsourcing she thinks that Medtronic will take a 25.5 percent share of U.S. market by the end of this year, 31.8 percent in 2015, and 40 percent in 2016. This beats her firm’s previous estimates for 24.8 percent, 24.4 percent, and 30.2 percent, respectively.
“We leave ACC even more convinced that the company will take greater U.S. TAVR market share from Edwards over the next 12-18 months than [Wall] Street expects,” Michael Weinstein, a medtech market analyst with JPMorgan Chase & Co., wrote in a note to investors.
But Edwards has more up its sleeve. The company is engaged in a European clinical trial comparing its lower-profile Sapien XT device against Medtronic’s CoreValve. The 241-patient trial revealed that 95.9 percent of the patients implanted with the balloon-expandable Sapien XT device achieved device success compared to 77.5 percent of patients confirming the same for the self-expandable CoreValve arm.
Right now, Edwards has three versions of its Sapien line—Sapien, Sapien XT, and the most recent design, Sapien 3, for which it has received investigational device exemption (IDE) approval from the FDA to initiate a single-arm, non-randomized clinical trial in the treatment of intermediate-risk patients with severe symptomatic aortic stenosis. The company also recently completed enrollment in its U.S. clinical trial studying the Sapien 3 valve in the treatment of high-risk or inoperable patients.
Edwards received CE mark for Sapien 3 in January. The target U.S. approval date is 2016. The company is working hard to keep up the momentum, with expectations to win FDA approval for its lower-profile Sapien XT before the end of the summer. In February, the company received CE mark for valve-in-valve procedures using XT for patients whose surgical mitral or aortic valves require replacement, and who are at extreme risk for surgery.
“Edwards’ Sapien XT has been anticipated for a couple of months to receive FDA approval, and that will shift things more in favor of Edwards,” Michael J. Mack, M.D., predicted to MPO. Mack, a thoracic surgeon, a member of the ACC board of trustees and medical director of cardiovascular surgery for Baylor Health Care System in Plano, Texas, said Sapien 3 has a much smaller delivery system than is currently available.
“Sapien 3 is really going to be a game-changer,” he said. “Medtronic is working on its Evolut R, which also has the potential to be a game-changer. It’s a slicker system that’s retrievable, and Medtronic is hoping to fast-track that. But the one to watch, I predict, will be Sapien 3. It has great results in terms of paravalvular leak. [Baylor] participates in virtually all of the [TAVR] trials, and I asked all of our cardiologists and surgeons which valve would they use if they could only have one, and most all of them said Sapien 3.”
Edwards, Mack said, has an “early lead in the clubhouse,” making it more difficult for Medtronic to catch up.
For Edwards, TAVR sales rose 28 percent from fiscal 2012 to 2013, from $552 million to $707 million. The company had total net sales in FY 2013 (ended Dec. 31) of a little more than $2 billion. For Medtronic FY 2014 (ended April 25) the company didn’t break out TAVR sales but noted that Structural Heart division revenue of $337 million grew 9 percent “driven by growth from the U.S. launch” of CoreValve.
Legal Heartache
The fiery competition between Edwards and Medtronic goes beyond positioning for market share—the companies recently ended a protracted patent battle.
In May, the companies reached a cross-license settlement over their TAVR technology in which they will dismiss all pending cases or appeals over TAVR valves for eight years. As part of the settlement, Minneapolis, Minn.-based Medtronic will pay a one-time fee of $750 million to Edwards. Medtronic also will make royalty payments to Edwards of up to $40 million annually for sales of its CoreValve device.
“With this resolution, we are pleased that Medtronic will be able to continue to provide the CoreValve System, as well as other products, to patients who need them in the U.S. and abroad without the overhang of any potential injunction or additional damages,” said John Liddicoat M.D., president of the Structural Heart business at Medtronic.
The two companies have been engaged in a bitter patent war over Sapien and CoreValve. The dispute is one of several between the two companies. They have battled it out in U.S. and European courts before about patents held by Edwards. One patent involved in is known as the Cribier patent, which also was the focus of a lawsuit in Europe that Medtronic won. Medtronic had appealed an earlier decision on the “Andersen” patent through the U.S. Supreme Court, which declined to hear it. In November, Medtronic resumed selling CoreValve in Germany after a court overturned an earlier ruling that Medtronic infringed on Edwards’ “Spenser” patent. A higher court said it would not enforce that ruling, after the European Patent Office said Edwards’ patent is not valid. The Andersen patent was granted in 1995. Edwards charged in 2008 that Medtronic infringed on the patent, and in 2010 a federal jury ruled in favor of Edwards, which was upheld on appeal. Edwards has requested a patent extension into early 2016.
Earlier this year, a judge imposed a temporary injunction limiting the sale of CoreValve in the United States but then delayed its implementation, which at the time was a short-term win for Medtronic. Neither company admitted that their products infringed any patents or that any patents were invalid. Edwards, based in Irvine, Calif., plans to contribute $50 million from the settlement to the Edwards Lifesciences Fund, which donates to various healthcare charities and causes.
Jockeying for Position
As Medtronic and Edwards play tug of war for market dominance, a number of other companies are looking for a piece of the action.
In May, St. Paul, Minn.-based St. Jude Medical Inc. kicked off a clinical trial to support FDA approval of its Portico re-sheathable transcatheter aortic valve system. The trial will enroll patients who have a high risk for open-heart surgery. The ability to fully re-sheath and precisely reposition a valve at the implant site prior to valve deployment helps achieve more accurate placement, which can simplify the implant procedure and minimize procedural risk for the patient, the company said. Patients at up to 40 U.S. sites will be randomized based on the appropriate access method, including transfemoral, transapical or subclavian. All trial participants will undergo a TAVR procedure receiving either a Portico valve or another commercially available TAVR valve. The 23-millimeter Portico and transfemoral delivery system received CE mark in 2012 and the 25-millimeter version received European approval in 2013. CE mark clinical trials currently are underway for additional valve sizes and delivery approaches.
Also in May, Santa Rosa, Calif.-based Direct Flow Medical Inc. received an IDE from the FDA to initiate the pivotal phase of the Salus trial for the company’s transcatheter aortic valve replacement systems at up to 30 sites. This technology, the company claims, is the first in class designed to treat aortic stenosis by replacing the patient’s native aortic valve, while minimizing the degree and frequency of aortic regurgitation. The fully repositionable and retrievable device is designed to treat patients with severe aortic stenosis who are at extreme surgical risk, while reducing the risk of post-procedural aortic regurgitation. The Direct Flow Medical system received the CE mark in January 2013 and currently is available commercially in Europe. Rather than a metal stent, the Direct Flow’s system incorporates a polymer frame, which is expanded using pressurized saline and contrast for placement, assessment and repositioning.
In October last year, Natick, Mass.-based Boston Scientific Corp.’s Lotus TAVR device received CE mark, and the company reported solid growth in its first quarter this year. The company expects to start IDE trials for the device in the United States in the second half of 2014.
International players are also making a push for part of the TAVR market.
In April, a startup firm called JenaValve Technology GmbH secured a $10 million extension to its Series C funding round, adding to a $62.5 million round the Munich, Germany-based firm closed last year. Unlike first-generation technologies, JenaValve’s device is equipped with clip-bearing feelers at its bottom that clamp onto tissue and lock the implant in place, a feature that improves procedural efficacy and cuts back on paravalvular leakage, the company said. JenaValve already has CE mark for its transapical system. The company is planning to launch a transfemoral model in Europe next year and is working to expand EU adoption—Germany in particular, which is the largest European market for TAVR.
“Market penetration is directly related to reimbursement,” Mack explained. “Germany is heavily penetrated [with TAVR] because of favorable reimbursement. Most other places in Europe aren’t as proactive as Germany has been with the procedure.”
Lausanne, Switzerland-based Symetis SA is a venture-backed company working on TAVR technology. The company has one device—called Acurate TA—with CE mark and has other iterations in its Acurate line of TAVR systems in clinical trials.
Braile Biomédica sells its Inovare line of aortic implants in its home country of Brazil.
“There’s certainly room for new players in this market, but taking away shares from Edwards and Medtronic will be difficult without substantially new and game-changing medical devices,” said Mack. “St. Jude, Boston [Scientific], Direct Flow, Symetis and others have good technology, but they’re in a position of playing catch-up and that’s always tougher.”
The Clinical Case
The aortic valve is located between the pumping chamber on the left side of the heart and the aorta, which is a major artery. The aorta carries oxygen-rich blood from the heart to the rest of the body. The valve should be closed while the heart is filling with blood. When the heart chamber squeezes to push blood into the aorta, the valve should open fully to allow blood flow.
Sometimes, particularly as we age, aortic stenosis—a narrowing of the aortic valve—can occur. This leads to increased stress and pressure on the heart muscle, which initially can result in chest discomfort or pain, shortness of breath, leg swelling, fatigue or fainting. Left untreated, the heart muscle can weaken over time resulting in worsening of symptoms and death. The most common cause of aortic stenosis is degenerative—age-related calcium deposits.
Aortic stenosis is the third most prevalent form of cardiovascular disease in the Western world after hypertension and coronary artery disease. Considered a potentially life-threatening condition, the aortic heart valve becomes calcified and does not open properly. Roughly 25 percent of people 65 and older have aortic valve thickening and 3 percent age 75 and older have severe stenosis.
Somewhat similar to a stent placed in an artery, the replacement aortic valve is delivered via catheter through several access methods. With TAVR, a fully collapsible (compressed down to the width of a pencil) replacement is moved to the natural valve site through a catheter primarily through one of two approaches: entering through the vein in the groin (called a transfemoral approach) or from between two ribs through the wall of the heart (called a transapical approach). Other delivery methods in today’s practice include subclavian (beneath the collar bone) and direct aortic (through a minimally invasive surgical incision into the aorta). Placement of the valve happens while the heart is still beating.
Once the new valve is put into place, it is expanded to push the old valve’s leaflets (the human aortic valve has three leaflets—delicate flaps—that stop blood flowing back into the left ventricle of the heart) out of the way and the tissue in the replacement valve takes over the job of regulating blood flow. The goal also is to prevent aortic regurgitation, a condition that occurs when the aortic valve doesn’t close tightly. Aortic valve regurgitation allows some of the blood that was just pumped out of the left ventricle to leak back into it.
Prior to the introduction of the TAVR option, surgeons had one primary path available to them—an open-heart procedure with a sternotomy in which an incision is made, the chest is cracked apart, the patient is placed on a heart-lung machine (stopping the heart), and the heart is opened to insert a new valve. Though it may sound positively barbaric compared to TAVR, it is still the most common method to replace a diseased valve for patients healthy enough for the procedure. Other options to treat valve narrowing include medication for the symptoms (though they don’t stop the progression of the disease) or balloon aortic valvuloplasty, in which a balloon is inserted into the aortic valve through a catheter that temporarily enlarges the valve opening but is temporary.
At present in the United States, TAVR primarily is only indicated for high-risk patients who are considered too frail to undergo open-heart surgery—but experts expect that indication to broaden as time goes on, additional studies are conducted, new device iterations are introduced, and safety of the procedure and technology are proven in the longer-term.
The benefits of the less-invasive procedure are that it’s much less traumatic for the body and, in most cases, it means a faster recovery time. A TAVR procedure, experts caution, is not without risks, but it provides a beneficial treatment alternative to people who just a few years ago may have had limited treatment options.
Market Leaders
The two 800-pound gorillas in the TAVR market at the moment are Edwards Lifesciences Inc. and Medtronic Inc. Though Edwards was first to market in the United States, Medtronic has been working to make up ground, and the two heavyweights have duked it out in what many analysts predict is a $3 billion global TAVR marketplace. The firms also have taken their battle to courtrooms internationally.
Edwards launched its Sapien valve in the European market in 2007. Approval by the U.S. Food and Drug Administration (FDA) came in 2011 for implantation using the transfemoral route. In 2012, the agency approved widened approval to those eligible for surgery (though still high risk) and use of the transapical route of entry. Sapien is a balloon-expanded device built on a stainless steel frame, and the three leaflets are made from tissue found in the outer wall of the cow heart (bovine pericardium).
Medtronic’s CoreValve device also was given CE mark in 2007, but Edwards didn’t have any competition in the U.S. market until January of this year when CoreValve received FDA approval. Like Sapien, CoreValve was approved for patients too frail to undergo traditional open-heart valve replacement. Notably, the Medtronic device was given the green light by the agency without the input of an independent device advisory panel, which usually is customary. In late 2013, the FDA announced it would not require an advisory committee to weigh in on whether the data supported approval, noting that data from the extreme-risk cohort of Medtronic’s clinical trial would be sufficient. CoreValve, which is a self-expanding device made of a nickel-titanium frame with a tri-leaflet valve created from porcine pericardium (derived from pig heart tissue), can be implanted via the femoral artery, subclavian or by direct aortic access. Medtronic anticipates FDA approval of the CoreValve System for high-risk patients sometime this summer.
Sapien and CoreValve come in a range of sizes, and both have had extremely solid clinical results.
Data presented at this year’s American College of Cardiology (ACC) annual meeting and simultaneously published in the New England Journal of Medicine showed that patient results with CoreValve system were superior to surgical aortic valve replacement at one year in patients at increased risk for surgery. It was the first time a prospective, randomized study has shown any transcatheter aortic valve to be superior to surgery. Upon reviewing the CoreValve Trial’s results for high-risk patients, the FDA 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. Thus is the rational behind Medtronic’s anticipation of FDA approval of the CoreValve System for high-risk patients this summer.
Following the ACC meeting, analysts were bullish on Medtronic’s prospects.
Joanne Wuensch, an analyst with BMO Capital Markets told Medical Product Outsourcing she thinks that Medtronic will take a 25.5 percent share of U.S. market by the end of this year, 31.8 percent in 2015, and 40 percent in 2016. This beats her firm’s previous estimates for 24.8 percent, 24.4 percent, and 30.2 percent, respectively.
“We leave ACC even more convinced that the company will take greater U.S. TAVR market share from Edwards over the next 12-18 months than [Wall] Street expects,” Michael Weinstein, a medtech market analyst with JPMorgan Chase & Co., wrote in a note to investors.
But Edwards has more up its sleeve. The company is engaged in a European clinical trial comparing its lower-profile Sapien XT device against Medtronic’s CoreValve. The 241-patient trial revealed that 95.9 percent of the patients implanted with the balloon-expandable Sapien XT device achieved device success compared to 77.5 percent of patients confirming the same for the self-expandable CoreValve arm.
Right now, Edwards has three versions of its Sapien line—Sapien, Sapien XT, and the most recent design, Sapien 3, for which it has received investigational device exemption (IDE) approval from the FDA to initiate a single-arm, non-randomized clinical trial in the treatment of intermediate-risk patients with severe symptomatic aortic stenosis. The company also recently completed enrollment in its U.S. clinical trial studying the Sapien 3 valve in the treatment of high-risk or inoperable patients.
Edwards received CE mark for Sapien 3 in January. The target U.S. approval date is 2016. The company is working hard to keep up the momentum, with expectations to win FDA approval for its lower-profile Sapien XT before the end of the summer. In February, the company received CE mark for valve-in-valve procedures using XT for patients whose surgical mitral or aortic valves require replacement, and who are at extreme risk for surgery.
“Edwards’ Sapien XT has been anticipated for a couple of months to receive FDA approval, and that will shift things more in favor of Edwards,” Michael J. Mack, M.D., predicted to MPO. Mack, a thoracic surgeon, a member of the ACC board of trustees and medical director of cardiovascular surgery for Baylor Health Care System in Plano, Texas, said Sapien 3 has a much smaller delivery system than is currently available.
“Sapien 3 is really going to be a game-changer,” he said. “Medtronic is working on its Evolut R, which also has the potential to be a game-changer. It’s a slicker system that’s retrievable, and Medtronic is hoping to fast-track that. But the one to watch, I predict, will be Sapien 3. It has great results in terms of paravalvular leak. [Baylor] participates in virtually all of the [TAVR] trials, and I asked all of our cardiologists and surgeons which valve would they use if they could only have one, and most all of them said Sapien 3.”
Edwards, Mack said, has an “early lead in the clubhouse,” making it more difficult for Medtronic to catch up.
For Edwards, TAVR sales rose 28 percent from fiscal 2012 to 2013, from $552 million to $707 million. The company had total net sales in FY 2013 (ended Dec. 31) of a little more than $2 billion. For Medtronic FY 2014 (ended April 25) the company didn’t break out TAVR sales but noted that Structural Heart division revenue of $337 million grew 9 percent “driven by growth from the U.S. launch” of CoreValve.
Legal Heartache
The fiery competition between Edwards and Medtronic goes beyond positioning for market share—the companies recently ended a protracted patent battle.
In May, the companies reached a cross-license settlement over their TAVR technology in which they will dismiss all pending cases or appeals over TAVR valves for eight years. As part of the settlement, Minneapolis, Minn.-based Medtronic will pay a one-time fee of $750 million to Edwards. Medtronic also will make royalty payments to Edwards of up to $40 million annually for sales of its CoreValve device.
“With this resolution, we are pleased that Medtronic will be able to continue to provide the CoreValve System, as well as other products, to patients who need them in the U.S. and abroad without the overhang of any potential injunction or additional damages,” said John Liddicoat M.D., president of the Structural Heart business at Medtronic.
The two companies have been engaged in a bitter patent war over Sapien and CoreValve. The dispute is one of several between the two companies. They have battled it out in U.S. and European courts before about patents held by Edwards. One patent involved in is known as the Cribier patent, which also was the focus of a lawsuit in Europe that Medtronic won. Medtronic had appealed an earlier decision on the “Andersen” patent through the U.S. Supreme Court, which declined to hear it. In November, Medtronic resumed selling CoreValve in Germany after a court overturned an earlier ruling that Medtronic infringed on Edwards’ “Spenser” patent. A higher court said it would not enforce that ruling, after the European Patent Office said Edwards’ patent is not valid. The Andersen patent was granted in 1995. Edwards charged in 2008 that Medtronic infringed on the patent, and in 2010 a federal jury ruled in favor of Edwards, which was upheld on appeal. Edwards has requested a patent extension into early 2016.
Earlier this year, a judge imposed a temporary injunction limiting the sale of CoreValve in the United States but then delayed its implementation, which at the time was a short-term win for Medtronic. Neither company admitted that their products infringed any patents or that any patents were invalid. Edwards, based in Irvine, Calif., plans to contribute $50 million from the settlement to the Edwards Lifesciences Fund, which donates to various healthcare charities and causes.
Jockeying for Position
As Medtronic and Edwards play tug of war for market dominance, a number of other companies are looking for a piece of the action.
In May, St. Paul, Minn.-based St. Jude Medical Inc. kicked off a clinical trial to support FDA approval of its Portico re-sheathable transcatheter aortic valve system. The trial will enroll patients who have a high risk for open-heart surgery. The ability to fully re-sheath and precisely reposition a valve at the implant site prior to valve deployment helps achieve more accurate placement, which can simplify the implant procedure and minimize procedural risk for the patient, the company said. Patients at up to 40 U.S. sites will be randomized based on the appropriate access method, including transfemoral, transapical or subclavian. All trial participants will undergo a TAVR procedure receiving either a Portico valve or another commercially available TAVR valve. The 23-millimeter Portico and transfemoral delivery system received CE mark in 2012 and the 25-millimeter version received European approval in 2013. CE mark clinical trials currently are underway for additional valve sizes and delivery approaches.
Also in May, Santa Rosa, Calif.-based Direct Flow Medical Inc. received an IDE from the FDA to initiate the pivotal phase of the Salus trial for the company’s transcatheter aortic valve replacement systems at up to 30 sites. This technology, the company claims, is the first in class designed to treat aortic stenosis by replacing the patient’s native aortic valve, while minimizing the degree and frequency of aortic regurgitation. The fully repositionable and retrievable device is designed to treat patients with severe aortic stenosis who are at extreme surgical risk, while reducing the risk of post-procedural aortic regurgitation. The Direct Flow Medical system received the CE mark in January 2013 and currently is available commercially in Europe. Rather than a metal stent, the Direct Flow’s system incorporates a polymer frame, which is expanded using pressurized saline and contrast for placement, assessment and repositioning.
In October last year, Natick, Mass.-based Boston Scientific Corp.’s Lotus TAVR device received CE mark, and the company reported solid growth in its first quarter this year. The company expects to start IDE trials for the device in the United States in the second half of 2014.
International players are also making a push for part of the TAVR market.
In April, a startup firm called JenaValve Technology GmbH secured a $10 million extension to its Series C funding round, adding to a $62.5 million round the Munich, Germany-based firm closed last year. Unlike first-generation technologies, JenaValve’s device is equipped with clip-bearing feelers at its bottom that clamp onto tissue and lock the implant in place, a feature that improves procedural efficacy and cuts back on paravalvular leakage, the company said. JenaValve already has CE mark for its transapical system. The company is planning to launch a transfemoral model in Europe next year and is working to expand EU adoption—Germany in particular, which is the largest European market for TAVR.
“Market penetration is directly related to reimbursement,” Mack explained. “Germany is heavily penetrated [with TAVR] because of favorable reimbursement. Most other places in Europe aren’t as proactive as Germany has been with the procedure.”
Lausanne, Switzerland-based Symetis SA is a venture-backed company working on TAVR technology. The company has one device—called Acurate TA—with CE mark and has other iterations in its Acurate line of TAVR systems in clinical trials.
Braile Biomédica sells its Inovare line of aortic implants in its home country of Brazil.
“There’s certainly room for new players in this market, but taking away shares from Edwards and Medtronic will be difficult without substantially new and game-changing medical devices,” said Mack. “St. Jude, Boston [Scientific], Direct Flow, Symetis and others have good technology, but they’re in a position of playing catch-up and that’s always tougher.”