A meeting of the Circulatory System Devices Panel was held on November 29, 2007. The Panel discussed the submission, made several specific recommendations, and voted on the premarket approval application (P070015) for the Abbott Vascular XIENCE™ V Everolimus Eluting Coronary Stent System.
The sponsor was seeking the following indications for use statement for the device: “The XIENCE™ V Everolimus Eluting Coronary Stent System is indicated for improving coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary artery lesions (length ≤ 28 mm) with reference vessel diameter of 2.5 mm to 4.25 mm.”
The XIENCE™ V Everolimus Eluting Coronary Stent System is comprised of a L-605 Cobalt Chromium (CoCr) alloy MULTI-LINK VISION® or MULTI-LINK MINI VISION™ stent mounted on a MULTI-LINK RX VISION® or MULTI-LINK MINI VISION™ RX Delivery System and coated with the drug Everolimus and polymer. The drug Everolimus is supplied by Novartis; an NDA for the drug under the trade name Certican® is currently under review with FDA. Novartis has provided FDA with the right to reference the drug safety information within the NDA in support of the XIENCE V PMA.
The XIENCE V product has four main components:
- Stent – cobalt-chromium alloy (approved as VISION or MINI VISION)
- Polymers - an acrylic polymer and copolymer of vinylidene fluoride and hexafluoropropylene (PVDF-HFP)
- Everolimus drug substance
- Over-the-Wire (OTW) or Rapid Exchange (RX) delivery system
The sponsor presented data from their clinical investigations SPIRIT FIRST, SPIRIT II and SPIRIT III trials. The SPIRIT III Clinical Trial was the pivotal trial for the XIENCE V EECSS and was composed of two parts; a US randomized clinical trial (RCT) and a non-randomized single-arm study. The non randomized study evaluated the XIENCE V 4.0 mm d iameter stent. In addition, a pharmacokinetic (PK) sub study was conducted in a subset of subjects in the RCT, 4.0 mm nonrandomized arm, and in a single-arm study conducted in Japan. Abbott Vascular also presented an ad hoc analysis on a subset of combined SPIRIT II and III subjects with 2 year follow-up as of October 30, 2007. Of the 603 subjects who were completers or early terminators, 422 subjects received XIENCE V and 181 subjects received TAXUS. The contribution of subjects according to the study in which they were enrolled is as follows:
- SPIRIT II: XIENCE V 186 patients, TAXUS 65 patients.
- SPIRIT III: XIENCE V 236 patients, TAXUS 116 patients
Despite several limitations for the 2 year analysis cohort presented by Abbott Vascular, the rates of additional cardiac death, myocardial infarctions and stent thrombosis events occurring between one and two years of follow-up were low.
Following presentations by the sponsor and the FDA, and after extensive deliberation, the Panel voted 9 to 1 in favor of “Approvable with Conditions.” The recommended conditions of approval are summarized as follows:
1. A post-approval study, the details of which to be worked out between the FDA and the applicant.
2. Labeling should include language regarding dual antiplatelet therapy use which is consistent with FDA’s proposed changes to currently approved drug-eluting stent labeling following the December 2006 Circulatory System Devices Panel meeting. Specifically, the labeling should describe the use of antiplatelet therapy in the clinical trials and suggest that use through 1 year may be beneficial per the published consensus guidelines.
Contact: James Swink, Executive Secretary,
(240) 276-4179 James.Swink@fda.hhs.gov
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