FDA Approves Second Generation Heart Valve From Edwards Lifesciences Reply

The next phase of the burgeoning and rapidly maturing transcatheter aortic valve replacement (TAVR) market has begun. Edwards Lifesciences announced on Monday afternoon that the FDA had approved its second generation Sapien XT TAVR device  for the treatment of high-risk and inoperable patients suffering from severe symptomatic aortic stenosis (AS).

Click here to read the full post on Forbes.

 

Medtronic To Pay Over $1Billion To Settle Patent Litigation With Edwards Lifesciences Reply

After years of protracted and often bitter litigation in the US and abroad, Edwards Lifesciences and Medtronic today announced a broad resolution to all their patent disputes over transcatheter heart valves.

Medtronic will pay more than a billion dollars over the course of the agreement, which lasts until April 2022.

Click here to read the full post on Forbes.

 

New Medtronic Heart Valve Threatened By Court Decision Reply

A legal injunction may severely limit the availability in the United States of Medtronic’s CoreValve device, which only received FDA approval earlier this year. The device received abundant praise recently when a large clinical trial demonstrated substantial advantages for CoreValve over traditional open-heart surgery.

The injunction is the latest episode in an ongoing patent war in which Edwards Lifesciences, which pioneered the field of transcatheter aortic valve replacement with its Sapien devices, has sought to hinder Medtronic from competing in the US and international markets.

Click here to read the full post on Forbes.

 

First TAVR Comparison Trial Favors Sapien XT Over CoreValve Reply

With two devices now approved for transcatheter aortic valve replacement (TAVR), the marketing battle has begun to win the hearts and minds of cardiologists. On Saturday at the ACC, Medtronic gained bragging rights showing the first mortality benefit for its CoreValve device. A similar improvement did not occur in the PARTNER trials with the Edwards Sapien device, but all the experts have warned against cross-trial comparisons. Now an actual randomized trial has emerged comparing the two platforms. The results favor the Sapien XT, but the size and scope of the trial mean that the discussion and debate will certainly continue.

Click here to read the entire post on Forbes.

 

 

FDA Grants Earlier Than Expected Approval For Medtronic’s CoreValve Reply

The FDA today approved Medtronic’s CoreValve transcatheter aortic valve replacement (TAVR) system for patients with severe aortic stenosis who are unable to undergo conventional open-heart surgery. The approval came several months ahead of expectations and without an FDA advisory panel meeting.

Click here to read the full post on Forbes.

CoreValve Family Sizing

Edwards CEO Sold Stock 2 Weeks Before It Tanked 2

(Updated) Earlier this week the stock of Edwards Lifesciences tanked after the company announced weak Sapien sales and lowered its sales guidance for the rest of the year. The stock, which had been trading in the low 80s for the past month, dropped a heartbreaking 22% on Wednesday in response to the news and closed at 65 on Thursday.

But Edwards chairman and CEO Michael Mussallem didn’t suffer along with his shareholders. As reported by GuruFocus, Mussallem sold 35,000 shares of his stock on April 10 at 83.37 per share netting him nearly $3 million. Another executive, the corporate VP of Japan and Intercontinental, Huimin Wang, sold 4,850 shares at $81.74 per share.

The dramatic drop in Edwards’ stock is another sign that the market for transcatheter heart valves has not grown as rapidly as many had expected. “Edward’s initial 2013 guidance clearly proved to be overly aggressive on U.S. TAVR sales as capacity constraints and the complexities of bringing a 20+ person team up the learning curve clearly tempered the adoption curve more than expected,” said a Leerink Swann analyst quoted by Bloomberg.

Update: I have been informed by Edwards that the recent sale was part of a predetermined plan to sell shares. Mussallem has sold 35,000 shares each month since June of 2012.

ACC And STS Break New Ground To Test TAVR For Unapproved Uses Reply

In a startling break with tradition, the American College of Cardiology and the Society of Thoracic Surgeons will manage and run their own clinical trials testing expanded uses for transcatheter aortic valve replacement (TAVR). The two medical groups have recently been granted an investigational device exemption (IDE) by the FDA for one such trial and hope to gain an IDE for at least two more trials. The news was first reported by The Gray Sheet (subscription required) on February 8.

The new development represents a significant enlargement of the TVT registry, already run by the ACC and STS, which tracks all TAVR usage in the US.

Click here to read the entire post on Forbes.

ACC STS TVT logo

TCT: Impressive Survival Benefit For TAVR In Inoperable Patients At 3 Years Reply

At the TCT meeting in Miami  Murat Tuzcu presented the latest findings from the PARTNER B trial comparing transcatheter aortic valve replacement (TAVR) with standard therapy in patients who are not considered eligible for surgical valve replacement. At three years the mortality advantage continued to grow for TAVR over standard therapy in patients who are not eligible for surgery.

All cause mortality at 3 years:

  • 80.9% in the control group versus 54.1% in the TAVR group (HR 0.53, CI 0.41-0.68, p<0.0001)

The difference between the groups has increased from from an absolute difference of 20.1% at 1 year (50.8% versus 30.7%) to 25% at 2 years (68% versus 43%) to 26.8% at 3 years. Here are the other 3 year endpoints reported by Tuzcu:

Rehospitalization at 3 years:

  • 75.7% versus 42.3% (HR0.39, CI 0.28-0.54, p<0.0001)

Mortality or reshospitalization at 3 years:

  • 93.1% versus 66.3% (HR 0.46, CI 0.36-0.58)

Mortality or stroke at 3 years:

  • 80.9% veruss 57.5% (HR 0.60, CI 0.46-0.77, p<0.0001)

The three year results, concluded Tuzcu, “continue to support the role of TAVR as the standard-of-care for symptomatic patients with aortic stenosis who are not surgical candidates.” As well, the results “underscore the importance of patient selection before TAVR and the need for aggressive management of illnesses after TAVR.”
Click here to read the press release from Edwards…

FDA Approves The Sapien Transcatheter Heart Valve For High Risk Patients 2

The FDA today approved an expanded indication for Edwards Lifesciences’ Sapien transcatheter heart valve (THV). The device can now be implanted in patients who are eligible for aortic valve replacement surgery but at high risk for serious surgical complications or death. Previously the Sapien valve was approved only for use in patients who were not eligible for surgery.

The FDA also said the device could be delivered through both the transfemoral route and the transapical route. Previously the device could only be delivered through the transfemoral route.

“Any procedure to replace the aortic valve carries the risk for serious complications, but for some patients with coexisting conditions or diseases that risk may be especially high,” said the FDA’s Christy Foreman, in an FDA press release. “The THV serves as an alternative for some very high-risk patients.” The FDA requires that before being deemed eligible for the Sapien valve a patient must be evaluated by a heart team, which includes a heart surgeon.

The new approval in high risk patients was based on findings from the PARTNER A trial. The earlier approval in non-operable patients was based on findings from the PARTNER B trial.

The FDA will continue to require Edwards to evaluate the Sapien device through a national registry.

Click here to read the FDA and Edwards press releases…

The Name Game: Why Did “TAVI” Suddenly Become “TAVR”? 2

One of the great, unexplained mysteries of the cardiology world in recent years is the sudden name change from TAVI  (transcatheter aortic valve implantation), which had been the universally-used name for the procedure during most of its development period, to TAVR  (transcatheter aortic valve replacement) about the time when the procedure edged closer to US approval.

Now, in a clever letter published in the Journal of the American College of Cardiology, Stacey Clegg and Mori Krantz “humbly suggest reversion to the archaic name transcatheter aortic valve implantation (TAVI).” When the procedure is explained to potential patients, they write:

We gracefully explain that we blow up a balloon, smash the old valve to the side, then implant a new one within their existing annulus. Their reaction is often one of bewilderment. This confusion is well founded. Webster’s dictionary defines replace as “to put something new in place of something else,” and implies filling a place once occupied by something removed. One does not have a muffler replaced at the local auto shop and expect to find the old one still in place. Technically, we are performing valve displacement. However, a valve displacement doesn’t sound like an advanced restorative therapy that marketing experts would embrace.

Clegg and Krantz write that TAVI was still in use in 2010 when the first PARTNER trial was published in the New England Journal of Medicine (“Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery”) but the acronym had been somehow magically transformed by 2011 when the second PARTNER trial was published in NEJM (“Transcatheter Versus Surgical Aortic-Valve Replacement in High-Risk Patients”).

Clegg and Krantz argue that “TAVI” should be restored as “the acronym of choice”:

Why does this matter? We contend that this is not merely semantic, because an accurate name for high-risk expensive procedures is pertinent to healthcare stake holders. It facilitates uniform communication among researchers, payers, regulators, clinicians, and, most importantly, patients. In a clinical landscape cluttered with jargon, we should strive toward verbal precision. Politicians, poets, and pollsters know that words matter. Powerful words launch social movements and even cultural revolutions. The right catch phrase also can launch a new product. However, there should be truth in advertising, and our regulatory bodies should be critical in determining if advertising is misleading or fails to disclose all the relevant facts.

There is one issue about the name change not addressed by Clegg and Krantz, and here we leave the idealistic world of semantics and philosophy and enter the hard-edged world of economics and finance. At the time of the change from TAVI to TAVR there were numerous rumors and speculations about the real reason for the change. Reimbursement for the procedure, the theory goes, would be much higher if it were based on a comparison with surgical replacement rather than surgical repair.

FDA Advisory Panel Recommends Expanded Indication For Sapien Transcatheter Heart Valve Reply

The FDA’s Circulatory System Devices Panel voted overwhelmingly on Wednesday to recommend an expanded indication for the Edwards Sapien Transcatheter Heart Valve in patients with symptomatic severe aortic stenosis who have high operative risk. The device is currently approved for use only in patients who are not surgical candidates.

The committee voted 10-2 that the Sapien device was safe, 12-0 that it was effective, and 11-0, with 1 abstention, that the benefits of the device outweigh the risks. Much of the day was spent by committee members wrestling with a number of difficult questions raised by FDA reviewers prior to the meeting, including the possible introduction of bias in the pivotal PARTNER A trial  because some patients randomized to surgery did not undergo surgery, the difficulty of evaluating the transapical approach due to the small number of patients randomized in that stratum of PARTNER, and the higher incidence of stroke and aortic regurgitation in the Sapien group.

Ultimately, however, the committee was persuaded by the totality of the data from PARTNER and additional nonrandomized data from patients who received the device under a continued access protocol. An additional strong source of reassurance for the panel was the safeguard provided by the TVT registry, a joint initiative from the Society of Thoracic Surgeons (STS) and The American College of Cardiology (ACC) that will closely monitor the use of TVR in clinical practice.

In sharp contrast to many recent advisory committee meetings, this panel was marked by the absence of drama and tension. A high point of the meeting for many observers was the public comment session. One speaker was a 92-year-old Sapien recipient who was a World War II veteran and prisoner or war who had survived the Bataan Death March. Another patient who spoke in favor of Sapien was the father of well-known Columbia University interventional cardiologist Jeffrey Moses, who helped develop the device. Moses said that he “wisely” chose to stay out of the case, though initially he did help persuade his father to accept the device after he refused to undergo surgery.

Related reading: 

Live Blog: FDA Advisory Panel For Edwards Sapien Transcatheter Heart Valve Reply

Here’s my live-blog of the FDA’s meeting of the Circulatory System Devices Panel to consider the premarket approval (PMA) application for the Edwards Sapien Transcatheter Heart Valve for use in patients with symptomatic severe aortic stenosis who have high operative risk. As reported here earlier this week, FDA reviewers have raised a number of questions about the safety and efficacy of the Sapien heart valve system. Here is a link to the FDA and Edwards briefing documents.

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Meeting adjourned.

6:00– The committee votes 10-2 that Sapien is safe, 12-0 that it is effective, and 11-0 (1 abstention) that the benefits outweigh the risks. 

5:55– Here’s questions 2 and 3:

VOTING QUESTION 2: Is there reasonable assurance that the Edwards SAPIENTM Transcatheter Heart Valve is effective for use in patients who meet the criteria specified in the proposed indication?

VOTING QUESTION 3: Do the benefits of the Edwards SAPIENTM Transcatheter Heart Valve for use in patients who meet the criteria specified in the proposed indication outweigh the risks for use in patients who meet the criteria specified in the proposed indication?

5:54– Wow– computer voting system is broken! They’re going to vote on paper.

5:48– After they finish the legal mumbo jumbo the voting will begin.

5:43– Getting close to the voting questions. Here’s #1:

VOTING QUESTION 1: Is there reasonable assurance that the Edwards SAPIENTM Transcatheter Heart Valve is safe for use in patients who meet the criteria specified in the proposed indication?

5:39– Edwards via Craig Smith giving their summary. He says he’ll be brief.

5:38– Now talking about study data that should be included in the labeling.

5:30– Now talking about post-approval studies to get further insights into stroke, aortic regurgitation, long term effectiveness, valve-in-valve, and gender issues.

5:28– Now discussing the totality of the evidence. Chairman states that the committee agrees that Sapien is safe and effective, with a number of caveats, such as stroke, TA/TF, gender, AR. (Why bother voting now?)

5:20– Committee now discussing informed consent and whether a more detailed informed consent form should be required. An additional piece of paper is not really the ideal solution.

5:15– Chairman summarizes that the FDA is concerned that valve-in-valve use may occur, but there’s no data to support this. Committee strongly encourages getting data on this and it should not be endorsed on the label. Committee wants to motivate the company to perform a separate clinical trial for this indication.
Click to continue reading…

FDA Reviewers Raise Questions About Sapien Heart Valve System 1

FDA reviewers have raised a number of questions about the safety and efficacy of the Sapien heart valve system. The review was published online ahead of Wednesday’s meeting of the Circulatory System Devices Panel meeting to evaluate the Sapien system for use in patients eligible but at high risk for aortic valve surgery. The Sapien system was previously approved in November 2011 for patients not considered surgical candidates for aortic valve replacement.

The FDA briefing document cites numerous examples of possible bias in the pivotal PARTNER A trial. The most serious problem appears to be caused by the high number of patients randomized to surgery who did not undergo surgery, including 7.9% who refused treatment or withdrew from the study. By contrast, only 0.3% of TAVR patients refused treatment or withdrew from the study. Surgical patients were also more likely to receive concomitant operations, another possible source of bias.

Another important topic of discussion will undoubtedly be the differences in outcome between patients receiving the transapical (TA) and transfemoral (TF) approaches. Unlike the TF stratum, where mortality was lower in the Sapien group, in the TA stratum mortality was higher in the Sapien group. Because there were only a relatively small number of patients in the TA group in the PARTNER trial, the panel will also consider TA patients treated outside the context of randomized trials.

The FDA reviewers were also concerned about stroke and aortic regurgitation. In the first 30 days the stroke rate was doubled in the Sapien group, and there were more strokes overall in the Sapien group in the TA stratum. Concern was also raised about the 53% of Sapien-treated patients who had mild or greater aortic insuficiency.

One interesting point raised by the FDA is that transcatheter aortic valve replacement (TAVR) is not nearly as noninvasive as many have been led to believe:
Click to continue reading…