Clinical trial and real-world outcomes of an endovascular iliac aneurysm repair with the GORE Iliac Branch Endoprosthesis (IBE)

Clinical trial and real-world outcomes of an endovascular iliac aneurysm repair with the GORE Iliac Branch Endoprosthesis (IBE) Jan MM Heyligers, PhD, FEBVS Consultant Vascular Surgeon The Netherlands

Clinical trial and real-world outcomes of an endovascular iliac aneurysm repair with the GORE Iliac Branch Endoprosthesis (IBE) Also on behalf of: Darren Schneider Ross Millner Nabil Chafké Jon Matsumura

Disclosures Speaker name: JMM Heyligers I have the following potential conflicts of interest to report: x Consulting Employment in industry Stockholder of a healthcare company Owner of a healthcare company x Other(s) I do not have any potential conflict of interest

Common iliac artery aneurysms (CIAA) Isolated common iliac artery aneurysms are a rare condition Often bilateral occurrence Sandu RS, et al. Semin Vasc Surg 2005 Dec;18(4):209-15 Brunkwall, J., et al. Vasc Surg 1989 Oct;10(4):381-4 Armon MP, et al. Eur J Vasc Endovasc Surg. 1998 Mar;15(3):255-7

Coil and cover internal iliac artery Occlude internal iliac artery and cover with endograft with sealing in the external iliac artery Buttock claudication: Unilateral 27% (range 14-50%) Bilateral 32% (range 13-80%) Erectile dysfunction: Unilateral 14% (range 11-45%) Bilateral 18% (range 11-50%) Colonic ischemia up to 3% Spinal ischemia <1% Verzini F, et al. J Vasc Surg 2009;49(5):1154-61 Farahmand et al. Eur J Vasc Endovasc Surg 2008;35(4):429-35 Lin PH, et al. Semin Vasc Surg 2009;22:193 Rayt HS, et al. Cardiovasc Intervent Radiol 2008;31:728 34

European and American Recommendations ESVS : Preserve at least one internal iliac artery (IIA); mandatory to avoid early complications SVS 2017 update guideline: strongly recommends use of an FDA iliac branched endograft to maintain IIA perfusion

GORE EXCLUDER IBE Device Only FDA approved Iliac Branched Device

The GORE IBE IDE trial Prospective, multicenter, single arm study Safety and effectiveness of the GORE EXCLUDER IBE as concomitant treatment with the GORE EXCLUDER in patients with CIAA and AIA Pivotal enrollment completed 2015 Continued access completed 2016 Bilateral treatment was only allowed in the continued access arm

GREAT Registry GORE initiated To monitor real world data

Global Enrollment Completed 2578 1845 400 193

Comparative data IDE and GREAT GREAT stipulates ISO definitions for a SAE: Reintervention Severe bodily deterioration Mortality Comparison of baseline characteristics and outcomes conducted with an unpaired t test or χ2 test KM survival curves analysis estimated freedom from mortality and reintervention in the IDE trial through 2 years P value <.05 significant

Baseline data IDE and GREAT Table I. Baseline demographic characteristics for 99 pivotal phase and continued access subjects enrolled in the Investigational Device Exemption (IDE) trial of the Gore Iliac Branch Endoprosthesis (IBE) and 92 subjects treated with the IBE in the Gore Registry for Endovascular Aortic Treatment (GREAT) Variable IDE GREAT P value N=99 N=92 Male 98/99 (99) 85/92 (92).02 Age 69.0 ± 9.3 72.2 ± 7.7.01 Weight 99.9 ± 20.1 89.2 ± 19.0 <.001 BMI > 30 53 (54) 34 (37).02 Height 179.5 ± 6.7 174.7 ± 7.2 <.001 CHF 16/99 (16) 6/92 (7).04 CABG 12/99 (12) 7/92 (8).30 Hypercholesterolemia 69/99 (70) 46/91 (51).007 Hypertension 82/99 (83) 66/92 (72).07 COPD 20/98 (20) 19/92 (21).97 Diabetes 24/98 (24) 18/92 (20).41 Renal insufficiency 7/99 (7) 10/92 (11).36 PVD 37/99 (37) 13/91 (14) <.001 ED 12/71 (17) 8/47 (17).99 Smoking 57/99 (58) 38/84 (45).10 Cancer 26/97 (27) 23/92 (25).78 Myocardial infarction 18/98 (18) -- -- BMI, body mass index; CABG, coronary artery bypass graft; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disorder; ED, erectile dysfunction; PVD, peripheral vascular disorder. Continuous data are expressed as mean ± standard deviation. Categorical data are expressed as numerator/denominator (percentage). P values are derived from unpaired t test and χ 2 test.

Procedural data IDE and GREAT Table III. Procedural characteristics in IDE trial and GREAT registry Variable IDE GREAT N=98 a N=92 P value Access method Percutaneous 54 (55) 37 (40).04 Open femoral access 40 (41) 45 (49).26 Conduit 1 (1) 7 (8).02 Percutaneous/open 3 (3) b 2 (2) c.70 Open/conduit 0 (0) 1 (1) c.30 No. with staged contralateral IIA embolization d 26 (27) -- -- No. with bilateral IBE placement 4/35 (11) e 13 (14).69 No internal iliac component placed 1 (1) f 6 (7).04 No IBC-compatible contralateral bridge component g 0 (0) 4 (4).04 Procedure survival 98 (100) 92 (100) >.99 Length of stay h 1.8 ± 1.6 4.3 ± 3.6 <.001 US only 1.8 ± 1.6 1.8 ± 2.0 >.99 OUS -- 5.4 ± 3.7 -- IIA, internal iliac artery; IBC, iliac branch component; IBE, iliac branch endoprosthesis; OUS, outside United States. Continuous data are expressed as mean ± standard deviation. Categorical data are expressed as number (percentage). P values are derived from unpaired t test and χ2 test. a Ninety-nine subjects were enrolled in the IDE trial, however, 1 subject was not treated with the device due to insurance. b Three IDE subjects with bilateral treatment (IBE placement in 1 limb and iliac exclusion in the contralateral limb) had percutaneous access in one limb and open access in one limb: in 2 of 3 subjects, open access was utilized on the side of IBE placement. c Three GREAT subjects had multiple access methods employed: none of these patients had bilateral IBE placement or branch procedures. d Due to the nature of data collection in GREAT, definitive data on staged procedures to exclude the contralateral IIA cannot be presented. e Only continued access subjects (n=35) were eligible for bilateral IBE placement in the IDE trial. f One subject had an iliac extender placed instead of the internal iliac component; this was one of two device deviations in the IDE trial, the other being one subject with an aortic extender placed bridging between the contralateral leg and the IBE. g Four GREAT subjects were implanted with contralateral limbs with distal diameters < 23 mm (only contralateral limbs 23 mm distal diameter are considered compatible with the IBC. h Twenty-eight GREAT subjects were treated in the US and 64 were treated outside the US. Mean length of stay was equivalent in US GREAT subjects and IDE subjects; OUS treatment was significantly longer, likely due to differing treatment protocols outside the U.S.

Outside IFU in GREAT Table IV. Outside IFU device usage in GREAT Variable GREAT N=92 Off-label per 1 criteria (IBE and/or Excluder) 51 (55) Off-label per 1 IBE criteria a 13 (14) Off-label per solely Excluder criteria b 38 (41) Off-label Excluder characteristics Non-IFU Excluder proximal diameter sizing 20 (22) Proximal aortic diameter outside treatment range 5 (5) Non-IFU Excluder distal diameter sizing 35 (38) Distal aortic diameter outside treatment range 11 (12) Infrarenal neck < 15 mm 3 (3) Aortic neck angle > 60 6 (7) Subjects were considered off label due to anatomic characteristics outside IFU-specified treatment ranges or due to device usage outside IFU specifications. Subjects inputted as off-label due to unapproved pathology (n=31) are not included in the counts above as unapproved pathology in GREAT may only indicate where site investigators did not input the iliac pathology into a patient s case report form. a Thirteen GREAT subjects had outside IFU usage of the IBE on 1 or more criteria; these patients may also have been off-label per Excluder criteria. Breakdown of number of patients off-label per solely IBE criteria is not available. b Thirty-eight patients had outside IFU usage of the Excluder device but were on-label for the IBE.

MAE in IDE and GREAT Procedure 1 Month 6 Months Major Adverse Events IDE trial N = 98 0 0 3 Deaths GREAT Registry N = 92 0 2 1 Stroke 1 Death (2,2%) (3,1%) 0

MAE in IDE and GREAT Procedure 1 Month 6 Months Major Adverse Events IDE trial N = 98 0 0 3 Deaths GREAT Registry N = 92 0 2 1 Stroke 1 Death (2,2%) (3,1%) 0 NO ARM

Reinterventions in IDE and GREAT Table V. Reinterventions through 6 months in IDE and GREAT subjects IDE N=96 1 month 6 months Cumulative GREAT N=60 P value No. requiring D-R reintervention 3 (3) 3 (5).55 2 (2) 3 (6) a.30 5 (5) 5 (5).92 No. with endoleak reintervention 0 (0) 1 (2).20 2 (2) 2 (4).61 2 (2) 3 (3).60 No. with thrombotic event reintervention 2 (2) 1 (2).85 0 (0) 0 (0) >.99 2 (2) 1 (1).60 No. with reintervention for other events b 1 (1) 1 (2).74 0 (0) 1 (2).20 1 (1) 2 (2).52 D-R, device-related. One-month reinterventions comprises all reinterventions occurring from day 0-59. Six month reinterventions comprises all reinterventions occurring between 60-242 days. Adjudication of events as device-related was per a clinical events committee in the IDE trial. In GREAT, sites adjudicate interventions as device-related and are reviewed internally by Gore. The full list of AEs has also been reviewed by study authors. Denominators consist of all subjects with any follow-up visit at 1 and 6 months; cumulative comparison denominators consist of all subjects implanted with the IBE device. a One subject required intervention at 1 month and 6 months. b Other events through 1 month consisted of a left external iliac artery dissection in the IDE trial. One GREAT subject required early and late reintervention for a persistent type B aortic dissection, and is counted in both windows in the category other events. Initial reintervention consisted of placement of an additional endograft; second reintervention consisted of implantation of EndoAnchors. IDE N=90 GREAT N=55 P value IDE N=98 GREAT N=92 P value

Reinterventions YES vs NO Table VI. Baseline and procedural variables in IDE & GREAT subjects undergoing reintervention vs IDE & GREAT subjects remaining intervention-free through 6 months Variable IDE & GREAT subjects with intervention N=10 IDE & GREAT intervention-free subjects N=181 P value Female 1 (10) 7 (4).37 Age 70.0 ± 6.9 70.6 ± 8.8.83 BMI > 30 5 (50) 82 (45).77 Diabetes 4 (40) 38/180 (21).16 Hypertension 9 (90) 139 (77).33 Hypercholesterolemia 8 (80) 107/180 (59).20 MI 3/5 (60) a, b 15/93 (16).01 Cardia arrhythmia 3 (30) 47 (26).78 CABG 2 (20) 17 (9).28 Renal insufficiency 2 (20) 15 (8).21 Smoking 5 (50) 91/173 (53).87 Cancer 3 (30) 46/179 (26).76 AAA 50 1/5 (20) a 36/94 (38).41 Procedural characteristics Percutaneous access c 1 (10) 92/179 (51).01 Open femoral access 6 (60) 81/179 (45).36 Surgical conduit 2 (20) 3/179 (2) <.001 Endovascular conduit 1 (10) 3/179 (2).07 Contralateral IIA exclusion 3/5 (60) a 33/94 (35).26 Bilateral IBE placement 1 (10) 16/180 (9).90 AAA, abdominal aortic aneurysm; BMI, body mass index; CABG, coronary artery bypass graft; IBE, iliac branch endoprosthesis; IIA, internal iliac artery; MI, myocardial infarction. Baseline demographics and all comorbidities with notable incidence in subjects with reintervention are reported above. a Variables where only IDE data can be considered. b An additional IDE subject had cardiac disease and remote MI occurring > 6 months prior to index procedure. c Three IDE subjects undergoing bilateral treatment (all consisting of unilateral IBE placement and contralateral IIA exclusion) had different access methods for each side. Subjects were attributed depending on access method on the side of IBE placement.

Sac Diameter change IDE Table VII. Core lab assessment of AAA & CIAA sac diameter changes in the IDE trial at 12 and 24 months Post-treatment follow-up period Variable 12 months, No. (%) 24 months, No. (%) N=80 N=46 AAA sac measurements 5 mm increase 2 (2) a 4 (9) a No change 63 (79) 32 (69) 5 mm decrease 15 (19) 10 (22) CIA sac measurements (ipsilateral to IBE placement) b 5 mm increase 0 (0) 0 (0) No change 56 (67) 26 (55) 5 mm decrease 28 (33) 21 (45) AAA, abdominal aortic aneurysm; CIA, common iliac aneurysm; IBE, iliac branch endoprosthesis; IIC, internal iliac component. AAA and CIA sac diameter change are per core lab measurement of CT images using the orthogonal view. Four subjects had multiple imaging assessments within the 365-day window. when this occurred, the visit nearest 365 days was utilized for assessment. Two subjects were ineligible for device effectiveness analyses due to 1) 1 subject not receiving both IBE components (iliac extender used instead of internal iliac component); and 2) 1 subject had concomitant femoral artery repair in violation of study exclusion criteria. a All subjects exhibiting AAA enlargement were imaged with type II endoleaks (or in 1 subject, a type II converted to indeterminate endoleak) at the time of sac diameter assessment. b Eighty-four CIAs (81 subjects) and 47 CIAs (46 subjects) had available core lab measurements of CIA diameter change at 12 and 24 months, respectively. At 12 months, there were 3 bilaterally treated subjects with available CIA measurements in both CIAs; at 24 months, 1 bilateral subject.

Type II endoleak IDE Supplemental Table I. Incidence and reinterventions for core lab identified type II endoleaks in the IDE trial through midterm follow-up Variable 1 month N=96 6 months N=89 12 months N=85 24 months N=49 Total no. subjects with type IIs a 58 (60) b 45 (51) c 39 (46) d 17 (35) No. requiring reintervention e 0 (0) 2 (2) 3 (4) 2 (4) f Total number type IIs 60 46 40 17 New type II 60 (100) 3 (7) 0 (0) 0 (0) Persistent type II 0 (0) 43 (93) 40 (100) 17 (100) No. spontaneously resolved before next FU 7 (12) 8 (17) 6 (15) -- a One subject each at 1 month and 12 months, and 2 subjects at 24 months, were assessed to have indeterminate endoleaks. Three of these subjects had indeterminate endoleaks previously assessed as type IIs at earlier follow-up, and 1 had indeterminate endoleak later assessed as a type II. b Fifty-seven subjects had type IIs observed at 1 month. Two subjects had multiple type IIs: 1 at the level of the Excluder trunk, 1 in the iliac branch. Of the 55 subjects with a singular type II observed at 1 month, 53 were observed at the level of the Excluder trunk. Two subjects exhibited a single endoleak at the level of the IBC/IIC. c Forty-five subjects presented with 46 type IIs: one subject had an additional type II at the level of the IBE. Of the 44 subjects with a singular type II, 43 were at the level of the Excluder trunk; 1 was at the level of the IBE. d Thirty-eight subjects exhibited 39 type IIs, with 1 subject exhibiting a second type II at the level of the left contralateral leg. e All reinterventions consisted of coil embolization of the endoleak. f Both interventions at 24 months were repeat coil embolizations for subjects undergoing initial type II intervention at 12 months. One of these subjects was considered to have an indeterminate endoleak by the core lab, however, the site considered it a type II and treated it with coil embolization.

Freedom from reintervention IDE 90.4%

Freedom from mortality IDE 91.8%

Conclusions IDE and GREAT Continued excellent outcomes for iliac aneurysm treatment using the GORE IBE through 2 years Low incidence of device-related thrombotic events requiring reintervention > 50% of cases was outside IFU within GREAT Comorbidity was more severe in IDE subjects

Conclusions IDE and GREAT MI < 6 Mo and non-percutaneous approach: more likely to undergo reinterventions Relatively high numbers of type II endoleaks, but only few interventions done/needed Sack expansion of CIAA was not observed @ 2 Yrs 45% sack decrease of 5 mm or more