FDA Review of Absorb Bioresorbable Stent Does Not Tip Hand Ahead of Tomorrow’s Advisory Panel Meeting

Clinical investigators and Abbott Vascular have a daylong appointment tomorrow with a Food and Drug Administration advisory committee to debate whether or not to recommend the approval of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) for clinical use in the United States.  

The company is seeking an indication for the dissolving stent based primarily on data from the ABSORB III clinical trial: “improving the 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.

Late last Friday, the FDA released briefing documents based on their internal evaluation of the data, but the report did not tip the agency’s hand as to whether or not reviewers there believe the BVS should be approved.

“The Panel’s review and recommendations will help FDA decide whether, based on the currently available data, the BVS demonstrates a reasonable assurance of safety and effectiveness when used in accordance with the proposed indication,” according to the reviewers. Overall, the FDA believes ABSORB III, the pivotal US trial considered by the FDA for device approval, was a “well conducted and monitored study that provided appropriate levels of patient safety oversight.”

As reported previously by TCTMD, ABSORB III was a head-to-head comparison of the Absorb BVS against a conventional everolimus-eluting cobalt-chromium stent (Xience, Abbott Vascular). 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 BVS and 6.1% with Xience, P for noninferiority = 0.007).

In their analysis of the data, the FDA reviewers draw attention to the rate of stent/scaffold thrombosis with BVS, noting that the rate at 1 year in the BVS arm was 1.54% compared with 0.74% among patients treated with Xience. “Although drawing conclusions from comparing event rates across different studies should be done with caution, the ABSORB III BVS stent thrombosis rate exceeds the rates observed in contemporary trials involving currently approved, widely used metallic DES,” according to the reviewers.

Since the publication of ABSORB III in 2015 in the New England Journal of Medicine, other meta-analyses, including those reported by TCTMD, showed an approximate two-fold higher rate of stent thrombosis with the Absorb BVS compared with conventional DES.

Another issue likely to emerge on Tuesday during the Circulatory System Devices Advisory Panel meeting, which is to be chaired by Richard Page, MD (University of Wisconsin School of Medicine, Madison), is vessel size. As the reviewers point out, a post hoc analysis of ABSORB III showed that treating vessels with a reference diameter less than 2.25 mm was associated with an increased rate of target lesion failure, MI, and stent thrombosis compared with individuals with vessels 2.25 mm or larger. This finding was finding even more pronounced in patients with diabetes, note the reviewers.

In the trial, adjunctive imaging with either IVUS, quantitative coronary angiograph or optical coherence tomography, was not required and as many as one in five treated patients had a reference vessel diameter less than 2.25 mm, according to the reviewers. During Tuesday’s meeting, the advisory committee members will be asked specifically whether they think proposed “precaution and warning statements” intended to address concerns in small vessels, including warning physicians not to implant the Absorb BVS in vessels less than 2.5 mm assessed by quantitative imaging, are adequate and acceptable.

Finally, the FDA panel will consider the length of follow-up in ABSORB III and whether it is sufficient to determine safety and efficacy, as well as whether the data are strong enough to support the sponsor’s strong recommendation that post-dilatation be performed when implanting Absorb BVS. The FDA advisory committee will discuss the outlines of a post-approval study should the stent be approved (such a discussion is not intended to imply device approval, adds the FDA).  

• Food and Drug Administration. FDA Executive Summary Prepared for the March 15, 2016 Meeting of the Circulatory System Devices Advisory Panel. http://www.fda.gov/AdvisoryCommittees/Calendar/ucm481684.htm.Published on: March 11, 2016. Accessed on: March 14, 2015. Available here.

Related Stories:

• Increased Early Risk of Stent Thrombosis with the Absorb Bioresorbable Scaffold
• ABSORB III: Novel Bioresorbable Scaffold as Good as Standard-of-Care DES
• ABSORB Trials Pit BRS Against Second-Generation DES