Circulatory System Devices Panel – October 10, 2007
A meeting of the Circulatory System Devices Panel was held on October 10, 2007. The Panel discussed the submission, made several specific recommendations, and voted on the premarket approval application (P060033) for the Medtronic Vascular Endeavor Zotarolimus Drug-Eluting Coronary Stent System and Over-the-Wire (OTW), Rapid Exchange (RX), and Multi-Exchange II (MX 2) Stent Delivery Systems.
The sponsor was seeking the following indications for use statement for the device: “ The Endeavor Zotarolimus-Eluting Coronary Stent System is indicated for improving coronary luminal diameter in patients with ischemic heart disease due to de novo lesions of length ≤ 27 mm in native coronary arteries with reference vessel diameters of ≥ 2.5mm to ≤ 3.5mm.”
The Endeavor Zotarolimus-Eluting CSS is a device-drug combination product comprised of device components (Driver™ and Micro-Driver™ Coronary Stents, and Endeavor delivery systems) and drug components (a formulation of zotarolimus and phosphorocholine polymer coating). The Endeavor product has four main components:
- Endeavor stent – cobalt-based alloy (MP35N)
- Phosphorylcholine (PC) polymer
- Zotarolimus drug substance (ABT-578)
- Endeavor Over-The-Wire (OTW), Rapid Exchange (RX), or Multi Exchange (MX2) delivery systems
The sponsor presented data from their clinical investigations ENDEAVOR I, II, II Continued Access, III, IV, and PK. The sponsor's pivotal study, ENDEAVOR II, was a prospective, multi-center, randomized, two-arm, double-blind trial compared to the Driver (bare metal) stent. ENDEAVOR III and IV were prospective, multi-center, randomized, two-arm, single-blind trials compared to the Cypher, and Taxus stents, respectively. The results of these individual trials as well as a post hoc pooled safety analysis of the entire Endeavor program (n=2088 Endeavor patients at 9 months; n=1287 Endeavor patients at 24 months; n=675 Endeavor patients at 36 months) were presented to demonstrate the product's safety and effectiveness profile.
Following presentations by the sponsor and the FDA, and after extensive deliberation, the Panel voted unanimously in favor of “Approvable with Conditions.” The recommended conditions of approval are summarized as follows:
- A ≥5,000 patient single-arm post-approval study compared to a performance goal derived from published bare metal stent data with endpoints of very late stent thrombosis and cardiac death + myocardial infarction, rigorous monitoring, and follow-up through at least 5 years.
- Labeling regarding antiplatelet therapy use which is consistent with FDA’s proposed changes to currently approved drug-eluting stent labeling following the December 2006 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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