Endologix, Inc. today announced a response to the U.S. Food and Drug Administration (FDA) update regarding Type III endoleaks with the AFX Endovascular AAA System.
Dr. Matt Thompson, Chief Medical Officer of Endologix Inc. commented, “On September 28, 2017, the FDA issued a letter to health care professionals (“HCPs”) regarding Type III endoleaks after endovascular aneurysm repair (“EVAR”). On June 19, 2018, the FDA issued an update to this letter to reinforce awareness of Type III endoleaks with Endologix’s AFX Strata System. Subsequently, on October 28, 2019, the FDA issued a further update as an FDA Safety Communication in response to an abstract from the Kaiser Integrated Health System, published in the Journal of the American College of Surgeons (Rothenberg et. al.). In this most recent update, the FDA notes that the data included in the abstract suggest that there may be a higher than expected risk of Type III endoleaks occurring with the use of AFX with Duraply and AFX2 endovascular grafts.”
Thompson continued, “The information from Rothenberg et. al, contains retrospectively collected data on 603 patients treated with the AFX Systems between 2011 and 2017 who had a 2.5% cumulative Type III endoleak rate at 2 years. The objectives of the study were described as to provide crude mid-term postoperative outcomes with the Endologix AFX/AFX2 devices. The FDA noted limitations with the data from Rothenberg et. al.in its October 28th update, including the small number of patients implanted with AFX2 (32 patients), the results not being stratified by Type IIIa and Type IIIb endoleaks, and the lack of a comparison of these results to the results from other endovascular graft systems. In our view, the small number of patients with AFX2 at 2 years (13 patients) prevents any clinically meaningful interpretation of these findings. The FDA update provides certain recommendations for patients implanted with AFX, including the need to undergo lifelong yearly surveillance, a practice that is already detailed in the AFX System’s instructions for use as well as in Endologix’s 2016 AFX safety notice and is standard practice with all aortic endografts.”
John Onopchenko, Chief Executive Officer of Endologix Inc. commented, “Our current commercially available versions of the AFX System: the AFX DuraplyTM and AFX2TM products, are manufactured using a different ePTFE processing methodology than AFX Strata and include additional product improvements. Endologix has a robust approach to monitoring the performance of our products through the use of multiple data sets that are benchmarked, compared against other commercially available endografts, and analyzed for concordance. These data include the LEOPARD trial (the only randomized controlled trial of EVAR providing Level 1 evidence), real world data from a vascular registry, our benchmarked MDR complaint data, and meta-analyses of current literature. All of the data sets we use are concordant and demonstrate, through the prospective analysis of 62,461 patients with the AFX system, that our AFX Duraply and AFX2 Systems currently achieve patient outcomes equivalent to other contemporary commercialized endografts, when assessed on an encompassing spectrum of clinical complications.”
Mr. Onopchenko continued, “These data also support our conclusion that changes to the ePTFE manufacturing process from Strata to Duraply, along with the AFX IFU updates, are associated with a reduction in the occurrence of Type III endoleaks for the AFX System. This finding is different from the Rothenberg et. al presentation at the American College of Surgeons, but we regard our datasets as being robust, prospectively collected, and with active contemporary comparators to set the results into appropriate context. We are committed to data transparency, and the data pertaining to our current analysis of the AFX System may be found in our Annual Clinical Updates, which the FDA has reviewed and subsequently referenced in its update: https://endologix.com/wp-content/uploads/2019/10/MM2165-Rev-01-Endologix-2016-2019-AFX-Clinical-Update.pdf. In particular, pages 33-48 detail the most recent results of the LEOPARD study, in which there are no Type IIIb endoleaks with the AFX2 system and no clinically meaningful difference in aggregated patient outcomes when compared to other commercial endografts. We remain confident that the AFX2 device is a safe and effective product when used as indicated, and we will work diligently to understand the outcomes presented by Rothenberg et. al as part of our continuing commitment to ensure that the interests of all EVAR patients, including those implanted with the AFX System, are being prioritized and addressed.”
Figure 1 demonstrates freedom from aneurysm related complications (ARC) in the LEOPARD trial. The LEOPARD trial is the only randomized controlled trial of EVAR devices that randomized 455 patients to receive AFX Duraply / AFX2 (235 patients) or contemporary comparator grafts (220 patients). The long-term performance of the AFX/AFX2 Bifurcated (with the DURAPLY ePTFE graft) is supported with 82.6% of subjects being free from ARC at 3-Years compared to the comparator group results of 79.8%. Aneurysm-Related Complications (ARC), is a composite of the most relevant EVAR-related outcomes. These included: peri-operative death (≤30 days), aneurysm rupture, conversion to open surgical repair, post-operative endoleaks, endograft migration (≥10mm), aneurysm enlargement (≥5mm compared to 1-month CT), endograft occlusion, and any reinterventions for device- or aneurysm-related complications.