FDA Panel Overwhelmingly Supports Absorb Bioresorbable Stent


(UPDATED) 
A US Food and Drug Administration advisory panel effectively gave an overwhelming endorsement of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) during a day-long session devoted to the investigational “dissolving” stent.

In total, nine panel members of the FDA’s Circulatory System Devices Panel felt the benefits of the Absorb BVS stent outweighed the risks. One panelist abstained from voting on the question of risk versus benefit. The panel members unanimously agreed the Absorb stent was an effective treatment in patients with ischemic heart disease, with all ten members believing there was a reasonable assurance of efficacy from the clinical trial data. Nine panelists felt there was a reasonable assurance the device was safe compared with just one who did not.

Advisory panel member George Ventrovec, MD (Medical College of Virginia, Richmond), said the wealth of data with the Absorb stent swayed his vote. “I feel better about this, because I think we understand this better than many things we’ve been very enthusiastic about in the past,” he said. “It’s certainly better studied, so that gives me a lot of comfort.”

Kristen Patton, MD (University of Washington, Seattle), gave an “optimistic yes” on the risk-versus-benefit question, saying she was “excited by the promise of this new technology.” Similarly, Richard Lange, MD (University of Texas, San Antonio), voted in favor, calling the results from the pivotal clinical trial “compelling.”

For John Somberg, MD (Rush University Medical Center, Chicago, IL), the data submitted by the sponsor provided a “reasonable assurance” of safety and efficacy, ultimately tilting the risk-benefit ratio in favor of the Absorb stent.

“I will say that the sponsor has a tremendous responsibility to carry out the studies that will prove the long-term benefits of the device and not just market on its potential, its hype, and its theoreticals,” said Somberg. “If they do that, I think they may revolutionize the field of interventional cardiology.”

Speaking on the issue of safety, Somberg did note there was a “signal” of concern: a higher rate of target-vessel MI and scaffold thrombosis with the Absorb BVS compared with the everolimus-eluting cobalt-chromium stent (Xience, Abbott Vascular) in patients with small vessels. He also noted that while the pivotal clinical trial testing the Absorb BVS stent showed the device was noninferior to Xience, the rates of target lesion failure (cardiac death, target-vessel MI, and ischemia-driven target lesion revascularization) and definite/probable scaffold thrombosis were numerically higher in patients treated with Absorb.

“I think the concern is that the device they compared it to is so effective that it rather stands out that in every one of the components of the primary endpoints—in fact, in every one of the considerations looked at for efficacy and safety—this device is not statistically different, but it’s a little less effective and has a little more adverse effects associated with it,” said Somberg. The bottom line, he said, is that while he believes the benefits of the Absorb stent outweigh the risks, the cardiovascular community will need to be very cautious in using the new device if its approved by the FDA.

The Advisory Panel Issues

The Absorb GT1 BVS system consists of an absorbable polymeric scaffold and polymer, both of which are completely broken down and dissolved within 36 months of implantation. Abbott Vascular is currently seeking an indication for the stent to improve coronary luminal diameter in patients with ischemic heart disease due to de novo coronary artery disease lesions. Specifically, the indication would include lesions 24 mm or less in length and vessels with a reference diameter ranging from 2.5 to 3.75 mm.

The issue of vessel size was particularly important to the advisory committee given the findings from the pivotal ABSORB III study, published in the New England Journal of Medicine and previously reported by TCTMD. Briefly, ABSORB III investigators enrolled 2,008 patients with stable or unstable angina and up to two de novo lesions, randomizing 1,322 patients to treatment with the Absorb stent and 686 patients to the Xience stent. The trial met the primary endpoint of noninferiority, with the two stents yielding similar rates of target lesion failure at 1 year (7.8% with Absorb BVS and 6.1% with Xience; P for noninferiority = 0.007).

However, when clinical events were stratified by reference vessel diameter, the analysis revealed that patients with a vessel less than 2.25 mm in diameter fared worse than patients with larger vessels. For those with a core laboratory-assessed reference vessel diameter less than 2.25 mm, the rate of target lesion failure at 1 year was 12.9% with Absorb and 8.3% with Xience, a difference driven by higher rates of target vessel MI. In addition, the rate of definite/probable stent thrombosis in these small vessels was 1.50% in the Xience arm compared with a scaffold thrombosis rate of 4.62% with Absorb.

Ralph Brindis, MD (Oakland Kaiser Medical Center, San Francisco, CA), said he did have concerns about the higher event rate in patients with small vessels. However, he said, the clinical investigators and study sponsor have proposed a mechanism to minimize such untoward complications: limiting the device to patients with vessels 2.5 mm or larger and recommending quantitative coronary angiography or IVUS in visually assessed vessels ≤ 2.75 mm to confirm appropriate sizing. In fact, the panel members suggested quantitative imaging be performed in an “eyeballed” vessel with reference vessel diameter of 3.0 mm or less. 

“I do believe this is a novel, breakthrough technology for patients undergoing PCI, and its rationale and judicious case selection and procedural management through physician education will be key to ensure safety and efficacy,” said Brindis.

Warren Laskey, MD (University of New Mexico School of Medicine, Albuquerque), was the lone vote against safety, saying the data did not provide a reasonable assurance the device is safe in patients outlined by the proposed indication. Specifically, Laskey said he had difficulty with the noninferiority study design, particularly the numerically higher rate of target lesion failure and scaffold thrombosis with Absorb. Despite these “reservations,” he believes, and voted in favor, that the benefit exceeds the risk.

What Does the Future Hold?

Speaking with TCTMD, James Blankenship, MD (Geisinger Medical Center, Danville, PA), the president of the Society for Cardiovascular Angiography and Interventions, said while ABSORB III showed numerically higher event rates compared with Xience, the event rates with Absorb stent are comparable with those of bare-metal stents and other drug-eluting stents still used in clinical practice. Importantly, it offers individuals a new option in an era of patient-centered decision-making.

In terms of the ideal candidate for Absorb, Blankenship said it would likely be a young patient who has a relatively straight, short, uncalcified artery to facilitate easy deployment of the stent and feels strongly about not having a permanent metal implant. “Some people don’t care, and for some people it’s a huge issue to have something in them, so the ideal patient would also be somebody who really sees a big advantage in the bioresorbable scaffold and derives a big psychological benefit from it,” said Blankenship.  

Abbott Vascular currently plans to follow patients in ABSORB III for 5 years and to continue with ABSORB IV, which will enroll an additional 3,000 patients. Combined, these two trials will attempt to address the question of superiority of Absorb compared with Xience.

“In other studies of drug-eluting stents, when they go out to 5 years or longer, there is a steady attrition rate of subsequent adverse events of roughly 1% per year,” said Blankenship. “The big question is whether Absorb will be able to beat that. That’s the great unproven hypothesis, that we’ll see the absence of subsequent events once we get past 2 or 3 years. Wishfully thinking, I hope that’s true, but I think everybody would have to admit that we just don’t have the answer to that question.”

The Absorb stent is widely available in Europe and has been implanted in more than 125,000 patients worldwide, according to Abbott Vascular.  


Source:
  • Ellis SG, Kereiakes DJ, Metzger DC, et al. Everolimus-eluting bioresorbable scaffolds for coronary artery disease. N Engl J Med 2016;373:1905-1915.

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