|Sapien 3 valve--Courtesy of Edwards Lifesciences|
CHICAGO--Edwards Lifesciences ($EW) is on track to be the first to meet the demand for TAVR implantation in an additional patient cohort following the success of the devices in high-risk patients with aortic stenosis who are too frail for open-heart surgery.
Practitioners at the American College of Cardiology meeting agreed that the Sapien TAVR has proved itself worthy of treating intermediate-risk patients with aortic stenosis, based on strong clinical trial data presented at the annual meeting of the Chicago conference. Edwards' stock has opened the day up 13% on the back of after-hours trading.
"The most important implication (of the clinical trial) is that TAVR is a very reasonable alternative to surgery in intermediate risk patients, similar to those included in this trial. It also appears that additional advantages may accrue to patients who have TAVR by transfemoral access," said study presenter and co-principal investigator Dr. Craig Smith of the Columbia University Medical Center.
With now-likely FDA approval expected in late 2016 or early 2017, the eligible population is set to more than double under the expanded indication. Bloomberg Intelligence senior healthcare analyst Jason McGorman said in an interview that he would not be surprised if the approval occurs earlier than expected. And it's likely to cover the latest generation Sapien 3, cardiologist said, citing a supplementary study of the device that was also presented at Chicago meeting.
Sean Messenger, principal analyst at Decision Resources Group told FierceMedicalDevices that he expects intermediate-risk TAVR patients to contribute $400 million in annual U.S. TAVR revenue by 2020. The number assumes that Medtronic's CoreValve achieves intermediate-risk approval in the second half of 2017.
DRG estimates that the U.S. TAVR market had revenues of $950 million in 2015. The firm's data indicate that Edward's Sapien 3 TAVR accounts for about 70% of the market, with Medtronic accounting for the rest, Messenger said.
Sapien XT trial details
But the randomized Partner II clinical trial utilized the second-generation Sapient XT. It demonstrated noninferiority to valves implanted via open-heart surgery among 2,032 intermediate-risk patients. Slightly more than 6% of patients experienced mortality or disabling stroke within 30 days of implantation, and 19.3% within two years, compared to 8% and 21.2%, respectively among those in the surgical group.
Although the surgery and TAVR implantation were shown to be comparable in intermediate-risk patients overall, the risk profile of specific adverse events was different. "Comparing an assortment of other clinical endpoints, reveals significantly more vascular complications with TAVR, but significantly more bleeding, renal dysfunction and new atrial fibrillation was seen with surgery, completing a pattern seen in Partner IA," Smith said.
The study found that patients who received the device via the conventional transfemoral (though the veins in the leg) approach experienced superior outcomes to those in the surgical group, but the data will also fuel what figures to an intense debate over the desirability of the transapical approach (through an incision in the chest) in intermediate-risk patients.
Smith said that for intermediate risk patients, the choosing between performing open-heart surgery and implanting a TAVR transapicaly is a "toss-up." It's long been known the transapical approach is less desirable, but some patients are unable to receive a TAVR transfemorally. While a quarter of the patients in the trial received the Sapien transapically, McGorman said that, currently, only about 10% of patients receive it that way, due to the emergence of smaller delivery catheters.
The average age of the intermediate-risk patients enrolled in trial was still quite high (almost 82) and half were frail. But Smith said the patients in the trial's surgery group had a lower mortality rate than those in previous high-risk control groups, meaning the patient selection criteria succeeded in enrolling lower-risk patients.
Separate study supports expanded indication for Sapien 3, too
Edwards also released nonrandomized data demonstrating that the Sapien 3 was superior to surgically implanted valves after one year based on a composite endpoint of primary endpoint of mortality, stroke and moderate or severe aortic regurgitation. The superiority claim is stronger than Sapien XT's demonstration of noninferiority, but also more uncertain because it isn't based on a randomized, controlled trial.
Study presenter Dr. Vinod Thourani of Emory Healthcare said during a press conference that the Sapien 3 study compared the surgical patients in the randomized Sapien XT trial to similar (or "propensity matched") patients in the Sapien 3 intermediate risk patient registry. The Sapien 3 patients had an all-cause mortality and disabling stroke rate of 8.4% at one year, compared to 16.6% among the surgery group patients.
Panelists Dr. Spencer King and Dr. John Carol said they expect the data to be sufficient for FDA approval of the Sapien 3 in intermediate-risk patients as well. As such, it would be impractical for the FDA to exclude the Sapien 3 from the expanded indication because it has replaced the XT in clinical usage on high-risk patients.
McGorman pointed out that the FDA agreed to use nonrandomized data to approve Medtronic's CoreValve in January 2014, albeit only among extreme-risk (or inoperable) patients; the high-risk indication was added later.
Low-risk indication next on the horizon
Despite the positive clinical trial results, "it remains true however, that long-term durability is uncertain and extrapolation of these findings to low-risk patients require further clinical trial validation," said Dr. Smith of Columbia University Medical Center during his presentation.
Such an approval would enable implantation of TAVRs in all aortic stenosis patients, and set the stage for the devices to replace surgical valves entirely, or close to it.
Testing the long-term durability of TAVRs thoroughly would require an impractically long clinical trial, Smith said: "I don't think anyone imagines constructing an all-comers or low-risk trial and following those patients for 15 years. My own guess is that just because there has to be (for regulatory reasons), there will be a low-risk trial, two have started actually, and we'll learn from those, and compare the early end-points, safety and efficacy, for TAVR vs. surgery. Meanwhile, the clock will be running on the long-term durability of previous generations of TAVRs. We'll have Sapiens and Sapien XTs out to 5, 6, 8, 10 years, and we'll fill it in from the back and go forward."
Edwards and Medtronic ($MDT) are both working on low-risk patients trials for their dueling TAVRs. Medtronic just enrolled its first patients in the trial. The company announced at the meeting that its CoreValve TAVR posted a superior all-cause mortality rate at two years among high-risk patients when compared to surgically implanted valves (15.0% vs. 26.3%).
But the weekend belonged to Edwards.