2014 ANNUAL CLINICAL UPDATE. TriVascular Inc. Ovation and Ovation Prime Abdominal Stent Graft Systems

Transcription

1 2014 ANNUAL CLINICAL UPDATE TriVascular Inc. Ovation and Ovation Prime Abdominal Stent Graft Systems

2 2014 ANNUAL CLINICAL UPDATE TriVascular Inc. Ovation and Ovation Prime Abdominal Stent Graft Systems Contents Abstract... 2 Device Description... 3 Section I: Clinical Experience... 4 Patient Status and Accountability... 4 Aneurysm-related Mortality... 7 Aneurysm Rupture... 8 Secondary Endovascular Procedures... 8 Conversion to Surgical Repair... 9 Endoleak... 9 Aneurysm Enlargement Stent Graft Migration Patency Device Integrity Section II: Worldwide Commercial Experience Section III: Explant Analysis Section IV: Instructions for Use (IFU) Clarification Section V: Summary and Conclusions Section VI: Brief Summary of Indications, Contraindications, Warnings and Precautions from IFU Page 1 of 23

3 Abstract TriVascular, Inc. is pleased to present the second edition of the Ovation and Ovation Prime Annual Clinical Update, which includes worldwide clinical and commercial experience. The Ovation Abdominal Stent Graft System Clinical Study was initiated in November 2009, and subjects will continue to be followed through 5 years. The Ovation device has been commercially available in Europe since CE Marking in August 2010 and in the U.S. since HDE approval in November 2011 (20mm device) and PMA approval in October 2012 (all sizes). The Ovation Prime device has been commercially available in Europe since June 2012 and in the U.S. since December The Ovation Pivotal Clinical Study includes 161 subjects: 111 in the United States, 30 in Germany and 20 in Chile. The Continued Access cohort includes 77 subjects in the United States. Both the Pivotal and Continued Access subjects are being followed in a Post-Approval Study (PAS) along with a de novo cohort that is currently enrolling in the United States. The de novo cohort will enroll a minimum of 59 subjects and up to 82 subjects in order to have 192 evaluable subjects at 5 years. As of July 25, 2014, fifteen (15) de novo subjects have been enrolled in the PAS study, and the data are included in the following sections. The PAS evaluates the real world data on the devices along with the long-term safety and effectiveness data. The data presented on the following pages continue to support the safety and effectiveness of the product with the following site or core lab-reported endpoints from the Pivotal, Continued Access and de novo cohorts: Aneurysm-related mortality to 365 days: 0.4% (1/252) Aneurysm rupture: Secondary endovascular procedures to 365 days: 5.6% (14/252) Conversion to surgical repair: Type I and III Endoleak: Aneurysm enlargement at 1 year: 1.4% (3/215) Stent Graft migration: Loss of Patency at 1 year: 0.5% (1/216) Loss of Device integrity at 1 year: 2.8% (6/211) Worldwide as of July 31, 2014, approximately 4,200 patients have been treated with the devices, and commercial experience is consistent with the clinical outcomes reported in the Clinical Study. TriVascular hopes that providing this data will assist in making informed treatment decisions for your patients diagnosed with Abdominal Aortic Aneurysms (AAA). Page 2 of 23

4 Device Description The TriVascular are endovascular devices delivered via a small diameter catheter to treat abdominal aortic aneurysms (AAAs). The stent graft is a modular configuration comprised of an aortic body section, iliac limbs, and iliac extensions as required. The aortic body is comprised of a proximal stent for suprarenal fixation and a low-permeability polytetrafluoroethylene (PTFE) graft. The stent is designed with integral anchors to enable fixation to the aortic wall. For delivery, the stent is in a compressed state within the catheter. When released from the compressed state, the stent expands to engage the vessel wall. To seal the proximal end of the graft and to provide support for the aortic body legs into which the iliac limbs are deployed, the graft body contains a network of inflatable rings that are filled with a liquid polymer that solidifies during the deployment procedure. The graft has a fill port that connects the fill network of the graft to the delivery catheter. The iliac limbs and extensions are comprised of a nitinol stent encapsulated in low-permeability PTFE, and the iliac limbs are deployed into the leg sections of the aortic body. The aortic body, the iliac limbs, and the iliac extensions are preloaded into delivery catheters (14F-15F OD, 13F 15F OD, and 13F 14F OD respectively). During stent graft deployment, the device is first positioned and the sheath is retracted. The proximal stent is then deployed using stent release knobs on the handle. The fill polymer is then mixed and delivered through the fill connector port to fill the sealing rings using the Autoinjector. The contralateral/ ipsilateral limbs are deployed into the legs of the aortic body, and if required, the iliac extensions are deployed into the limbs. The fill polymer radiopacity dissipates over time and may not be visible on fluoroscopy, X-ray or CT beyond 1-2 months post-implant. Page 3 of 23

5 Section I: Clinical Experience The data presented below include available subject information from the TriVascular Ovation/Ovation Prime Abdominal Stent Graft System post-approval study cohort as of July 25, The data include Pivotal and Continued Access subjects from the Ovation clinical study and data from subjects enrolled in the PAS de novo cohort. Patient Status and Accountability Of 161 enrolled Pivotal subjects, 152 subjects were eligible for a 12-month follow-up visit, 138 were eligible for a 2 year follow-up visit, 129 were eligible for a 3 year follow-up visit, and 39 were eligible for a 4 year follow-up visit. Twenty-four (24) subjects died, 14 withdrew, and 4 were lost to follow-up. Table 1. Subject and Imaging Accountability through 4 year follow-up, Pivotal Subjects Interval (Analysis Window) Subject follow-up Subjects with imaging performed (Core Lab) Subjects with adequate imaging to assess the parameter (Core Lab) Subject events occurring before next visit Eligible Clinical Follow-up Imaging Followup CT Imaging KUB imaging Aneurysm size increase Endoleak Migration Stent Integrity No implant Conversion to surgery Death Withdrawal Lost to follow-up Not due for next visit yet Originally Enrolled Events after implant but before a 1 Month visit 1 1 Month (Day 1-90) (10) (101%) 2 (10) 157 (98%) 153 (96%) 157 (98%) Events after 1 Month visit but before a 6 Month visit Month (Day ) (99%) 156 (99%) 154 (98%) 150 (96%) 152 (97%) 150 (96%) 154 (98%) 150 (96%) Events after 6 Month visit but before a 12 Month visit Month 1 (Day ) (10) 152 (10) 150 (99%) 147 (97%) 150 (99%) 143 (94%) 150 (99%) 147 (97%) Events between 12-month and 2 year visit Page 4 of 23

6 2 year (Day ) 138 (99%) (96%) (96%) (89%) (96%) (88%) (96%) (82%) Events between 2 year and 3 year visit year (Day ) 129 (98%) (94%) (88%) (83%) (88%) (82%) (88%) (82%) Events between 3 year and 4 year visit year (Day ) (77%) (69%) (51%) (49%) (51%) (49%) (51%) (49%) Data analysis sample size varies for each of the time points above and in the following tables. This variability is due to subject availability for followup as well as quantity and quality of images available from specific time points for evaluation. For example, the number and quality of images available for evaluation of endoleak at 6 months is different than the number and quality of images available at 12 months due to variation in the number of image exams performed, the number of images provided from the clinical site to the Core Lab, and or the number of images with acceptable evaluation quality 1 In cases where 12 month imaging follow-up data was not available, subsequent imaging follow-up data were used. 2 One subject expired before hospital discharge and is not eligible for 1 month visit, but has imaging follow-up in 1-90 days time period post procedure. Of 77 enrolled Continued Access subjects, 70 subjects were eligible for a 12-month follow-up visit, 55 were eligible for a 2 year follow-up visit, and 4 were eligible for a 3 year follow-up visit. Seven (7) died, 4 withdrew, and 1 was lost to follow-up. Table 2. Subject and Imaging Accountability through 3 year follow-up Visit, Continued Access Subjects Interval (Analysis Window) Subject follow-up Subjects with imaging performed (Core Lab) Subjects with adequate imaging to assess the parameter (Core Lab) Subject events occurring before next visit Eligible Clinical Follow-up Imaging Follow-up CT Imaging KUB imaging Aneurysm size increase Endoleak Migration Stent Integrity No implant Conversion to surgery Death Withdrawal Lost to follow-up Not due for next visit yet Originally Enrolled 77 0 Events after implant but before a 1 Month visit 1 Month (Day 1-90) (99%) 76 (99%) 76 (99%) 77 (10) 73 (95%) 77 (10) Page 5 of 23

7 Events after 1 Month visit but before a 6 Month visit Month (Day ) (10) 73 (99%) 71 (96%) 70 (95%) 70 (95%) 66 (89%) 71 (96%) 70 (95%) Events after 6 Month visit but before a 12 Month visit Month (Day ) (94%) 65 (93%) 65 (93%) 64 (91%) 65 (93%) 62 (89%) 65 (93%) 64 (91%) Events between 12- month and 2 year visit year (Day ) (91%) 51 (91%) 46 (82%) 46 (82%) 46 (82%) 42 (75%) 46 (82%) 46 (82%) Events between 2 years and 3 year visit year (Day ) 4 4 (10) 4 (10) 4 (10) 2 (5) Data analysis sample size varies for each of the time points above and in the following tables. This variability is due to subject availability for follow-up as well as quantity and quality of images available from specific time points for evaluation. For example, the number and quality of images available for evaluation of endoleak at 6 months is different than the number and quality of images available at 12 months due to variation in the number of image exams performed, the number of images provided from the clinical site to the Core Lab, and or the number of images with acceptable evaluation quality 4 (10) 4 (10) 4 (10) 2 (5) Of 15 enrolled de novo subjects, 14 subjects were eligible for a 1-month follow-up visit. None of the subjects died, withdrew, or were lost to follow-up. Page 6 of 23

8 Table 3. Subject and Imaging Accountability through 1 month follow-up Visit, de novo Cohort Interval (Analysis Window) Subject follow-up Subjects with imaging performed (Site) Subject events occurring before next visit Eligible Clinical Follow-up Imaging Follow-up CT Imaging KUB imaging No implant Conversion to surgery Death Withdrawal Loss to follow-up Not due for next visit yet Originally Enrolled Events after implant but before a 1 Month visit 1 Month (Day 1-90) (71%) 14 (10) 11 (79%) 13 (93%) Data analysis sample size varies for each of the time points above and in the following tables. This variability is due to subject availability for follow-up as well as quantity and quality of images available from specific time points for evaluation. 1 One subject did not have a procedure form entered at the time of this data extraction so is not counted as eligible for follow-up at this time. Aneurysm-related Mortality Aneurysm-related mortality (defined as death by any cause within 30 days of the index procedure) for the combined Pivotal, Continued Access, and de novo cohorts through 365 days post-treatment was 0.4% (1 of 252). One (1) aneurysm-related death occurred in the Pivotal cohort within 30 days of the index procedure due to abdominal sepsis and disseminated intravascular coagulation. During the index procedure, the site reported a polymer leak from the Aortic Body delivery catheter due to a disconnection between the Aortic Body and the delivery catheter, and the patient experienced a hypersensitivity reaction. The device component responsible for the disconnection was modified, and no additional disconnections were reported after incorporating the modification. The event was adjudicated by the Clinical Events Committee (CEC) to be procedure-related and not device-related. Page 7 of 23

9 Table 4. Aneurysm-related Mortality AAA-related mortality 1 Treatment to 365 days Treatment to 30 days 31 to 365 days 366 to 730 days 731 to 1095 days 1096 to 1460 days 1461 to 1825 days Pivotal 0.6% (1/161) 0.6% (1/161) (0/159) (0/154) (0/138) (0/97) (0/11) Continued Access (0/77) (0/77) (0/77) (0/66) (0/36) (0/1) 0/0 De novo (0/14) (0/14) (0/5) 0/0 0/0 0/0 0/0 TOTAL COMBINED 0.4% (1/252) 0.4% (1/252) (0/241) (0/220) (0/174) (0/98) (0/11) 1 Aneurysm-related mortality defined as death from rupture of the abdominal aortic aneurysm or from any procedure intended to treat the AAA. If a death occurred within 30 days of any procedure intended to treat the AAA or within the hospital stay if the subject was not discharged within 30 days, then it is presumed to be aneurysm-related. Aneurysm Rupture As of the date of this report, no AAA rupture has been reported for a study subject included in the post-approval study. Secondary Endovascular Procedures A total of 12 AAA-related secondary procedures were performed in the Pivotal cohort during the treatment to 365 days follow-up period in 10 subjects (6.2%). The secondary interventions were performed to treat the following outcomes: endoleak (2 procedures for type IA, 1 for type IB and 3 for type II), aortic body stenosis (3 procedures), iliac limb occlusion (2 procedures), and iliac limb stenosis (1 procedure). One (1) subject had a single intervention to treat two outcomes (type IA endoleak and aortic body stenosis). Five (5) AAA-related secondary procedures were performed in the Continued Access cohort during this same period in 4 (5.2%) subjects for endoleak: one (1) subject had a procedure to treat type IA and type II endoleaks; one (1) subject was treated for type IB endoleak, and two (2) subjects were treated for type II endoleak. In the 366 to 730 days follow-up period, five (5) Pivotal subjects had AAA-related secondary procedures: four (4) to treat type II endoleaks and one (1) to treat a type IA endoleak. Two (2) Continued Access subjects had AAA-related secondary procedures: one (1) subject had a procedure to treat aortic body occlusion, and one (1) subject was treated for type II endoleak. In the 731 to 1095 days follow-up period, five (5) Pivotal subjects had AAA-related secondary procedures to treat type II endoleaks and one (1) subject had a AAA-related secondary procedure to treat an iliac limb occlusion. Two Continued Access subjects had AAA-related secondary Page 8 of 23

10 procedures to treat endoleak: one (1) subject had a procedure to treat a type IB endoleak, and one (1) subject had a procedure to treat a type II endoleak. In the 1096 to 1460 days follow-up period, three (3) Pivotal subjects were treated for type II endoleaks, and two (2) subjects were treated for iliac limb occlusion. The subjects with stenosis or occlusion were treated with stenting, balloon angioplasty, thrombolysis, and/or thrombectomy, and two subjects were treated with a fem-fem bypass (one after an unsuccessful thrombectomy). The Continued Access subject had a resulting hematoma that required additional treatment. The other subjects have had no additional re-interventions or clinical sequelae reported after the secondary procedure. Table 5. AAA-related Secondary Procedures AAA-related Secondary Procedures 1 Pivotal subjects Continued Access De novo Cohort TOTAL COMBINED Treatment to 365 days 6.2% (10/161) 5.2% (4/77) (0/14) 5.6% (14/252) Treatment to 30 days 1.2% (2/161) (0/77) (0/14) 0.8% (2/252) 31 to 365 days 5. (8/159) 5.2% (4/77) (0/5) 5. (12/241) 1 Two subjects had a single intervention to treat two outcomes. 366 to 730 days 3.2% (5/154) 3. (2/66) 731 to 1095 days 4.3% (6/138) 5.6% (2/36) 1096 to 1460 days 5.2% (5/97) (0/1) 0/0 0/0 0/0 0/0 0/0 3.2% (7/220) 4.6% (8/174) 5.1% (5/98) 1461 to 1825 days % (n/n) (0/11) (0/11) Conversion to Surgical Repair No surgical conversions were reported under the post-approval study. Endoleak No type I, III, or IV endoleaks were identified by the imaging core laboratory at the follow-up intervals through 4 years. Endoleaks that were detected between follow-up visits were treated as summarized in Secondary Endovascular Procedures above. Type II endoleak incidence rate at the 1 year follow-up visit for the combined Pivotal and Continued Access cohorts was 34.6%. At 2 years, the combined type II endoleak rate in the Pivotal and Continued Access cohorts was 34.4% (56/163), and at 3 years, the type II endoleak rate was 30. (33/110). The clinical trial protocol-specified CT methodology may have influenced endoleak detection rates, thereby increasing the reported rates. Slice thicknesses of 0.6 to 2.0 mm were recommended in the protocol, which were ultimately reconstructed by the imaging core laboratory to 2.0 mm for analysis. In contrast, 3-5 mm slices are commonly utilized in the Page 9 of 23

11 follow-up of patients treated with endovascular stent grafts, which are not as effective in detecting small leaks. As the typical type II endoleak identified in this study was small (mean volume < 1 cc), the endoleak detection rate in the study was likely due, in part, to high quality imaging. No type I, III, or IV endoleaks were identified by the sites for the de novo cohort. The type II endoleak at 30 days for the de novo cohort is 4/14. Table 6. Imaging Core Lab-reported Endoleaks Endoleak Treatment to 1 year 1,2 Endoleak 3 Pivotal subjects 47.8% (75/157) Continued Access 44% (33/75) TOTAL COMBINED 46.6% (108/232) Type I Pivotal subjects (0/157) Continued Access (0/75) TOTAL COMBINED (0/232) Type II Pivotal subjects 46.5% (73/157) Continued Access 42.7% (32/75) TOTAL COMBINED 45.3% (105/232) Type III Pivotal subjects (0/157) Continued Access (0/75) TOTAL COMBINED (0/232) Type IV Pivotal subjects (0/157) Continued Access (0/75) TOTAL COMBINED (0/232) Indeterminate origin Pivotal subjects 8.3 % (13/157) 30 day 1,2 44.4% (68/153) 42.5% (31/73) 43.8% (99/226) (0/153) (0/73) (0/226) 40.5% (62/153) 41.1% (30/73) 40.7% (92/226) (0/153) (0/73) (0/226) (0/153) (0/73) (0/226) 6 month 1,2 42% (63/150) 37.9% (25/66) 40.7% (88/216) (0/150) (0/66) (0/216) 38. (57/150) 31.8% (21/66) 36.1% (78/216) (0/150) (0/66) (0/216) (0/150) (0/66) (0/216) 1 year 1,2 39.2% (56/143) 35.5% (22/62) 38. (78/205) (0/143) (0/62) (0/205) 35.7% (51/143) 32.3% (20/62) 34.6% (71/205) (0/143) (0/62) (0/205) (0/143) (0/62) (0/205) 2 year 1,2 38. (46/121) 40.5% (17/42) 38.7% (63/163) (0/121) (0/42) (0/163) 35.5% (43/121) 31. (13/42) 34.4% (56/163) (0/121) (0/42) (0/163) (0/121) (0/42) (0/163) 3 year 1,2 34.9% (37/106) 25% (1/4) 34.5% (38/110) (0/106) (0/4) (0/110) 30.2% (32/106) 25% (1/4) 30. (33/110) (0/106) (0/4) (0/110) (0/106) (0/4) (0/110) 3.9% % 2.5% 4.7% (6/153) (6/150) (5/143) (3/121) (5/106) Continued Access 6.7% 1.4% 6.1% 4.8% 9.5% 0/0 4 year 1,2 % (n/n) 31.6% (6/19) 0/0 31.6% (6/19) (0/19) 0/0 (0/19) 15.8% (3/19) 0/0 15.8% (3/19) (0/19) 0/0 (0/19) (0/19) 0/0 (0/19) 15.8% (3/19) Page 10 of 23

12 Endoleak Treatment to 1 year 1,2 30 day 1,2 6 month 1,2 1 year 1,2 2 year 1,2 3 year 1,2 4 year 1,2 % (n/n) (5/75) (1/73) (4/66) (3/62) (4/42) (0/4) TOTAL COMBINED 7.8% 3.1% 4.6% 3.9% 4.3% 4.5% 15.8% (18/232) (7/226) (10/216) (8/205) (7/163) (5/110) (3/19) Data provided by imaging X-ray core lab. Analysis windows are: 1month (1 to 90 days), 6 months (91 to 304 days), 1 year (305 to 547 days), 2 years (548 to 911 days), and 3 years (912 to 1277 days), and 4 years (1278 to 1642). 1 Denominator at each time point is the number of subjects with at least one readable scan in the time interval. 2 Numerator may not equal the sum of type endoleaks if more than one type was identified in the same subject. 3 Endoleaks in this section include all subjects with any type of endoleak. The numerator may not equal the sum of all types of endoleaks if more than one type was identified in the same subject. TriVascular conducted additional subset analyses of type II endoleaks to evaluate potential contributing factors: the analyses appear to show a correlation between subject geographic location and type II endoleak rates. At 3 year follow-up, the U.S. subjects had a type II endoleak rate of 23.2% (16/69); the Germany subjects had a type II endoleak rate of 26.1% (6/23), and the Chile subjects had the highest type II endoleak rate of 61.1% (11/18). TriVascular is evaluating possible contributing factors for the higher rates, including subject medical histories, concurrent medications, and anatomical factors. Aneurysm Enlargement All subjects with aneurysm diameter enlargement (defined as AAA diameter increase > 5 mm) had a type II endoleak reported by the core lab during one or more follow-up visits. As described below, some of the subjects have been treated for the type II endoleaks, and the aneurysm size continues to be monitored. No type I or type III endoleaks have been reported in any subjects by the core lab. Aneurysm diameter enlargement identified by the imaging core laboratory at 12 months posttreatment (compared to the 1-month imaging) was reported in two (2) Pivotal and one (1) Continued Access subject. The first Pivotal subject had AAA diameter increase reported by the imaging core laboratory at the 12 month assessment, but the site reported a 3 mm decrease in AAA diameter at the 12 month assessment. This subject was treated with coil embolization. The second Pivotal subject had enlargement reported at 6 months (increase of approximately 6.5 mm from baseline), and the aneurysm size slightly decreased by the 12 month visit (overall 12 month increase of 5.2mm from baseline). This subject has not received treatment for the enlargement, and the aneurysm size continues to decrease at the 2 year follow-up visit (overall 2 year decrease of 0.5mm from baseline). Of the five (5) Pivotal subjects with aneurysm diameter enlargement at the 2 year follow-up, two (2) of the subjects were treated with coil embolization; both subjects have AAA diameter increasing from baseline at the 3 year follow-up, and one subject is reported with AAA diameter increase at the 4 year follow-up. A third subject was treated with thrombin injection and stenting, the fourth subject was treated with embolization techniques, and the fifth subject has Page 11 of 23

13 not received treatment. These subjects have AAA enlargement at the 3 year follow-up, and all subjects continue to be monitored. Of the thirteen (13) Pivotal subjects with an aneurysm diameter increase at the 3 year follow-up, four (4) subjects (in addition to the four (4) subjects described above) were treated with embolization techniques and/or thrombin injection. The subjects continue to be monitored. Four (4) Pivotal subjects had aneurysm enlargement at the 4 year follow-up: three (3) subjects had continuing enlargement from the 3 year follow-up period. One Continued Access subject had aneurysm enlargement reported at the 1 year and 2 year follow-up, and the subject has not been treated to date. Of the three (3) additional Continued Access subjects with aneurysm diameter enlargement at the 2 year follow-up, one (1) subject has not received an intervention, and two (2) subjects were treated with coil embolization. All subjects continue to be monitored. De novo subjects have been followed to 43 days post-implant; therefore, there are no data to report for this cohort. Page 12 of 23

14 Table 7. AAA Diameter Change AAA Diameter Change AAA diameter increase > 5mm 1 Pivotal subjects 0.7% (1/153) Continued Access (0/69) TOTAL 0.5% COMBINED (1/222) AAA diameter change <= 5mm 1 Pivotal subjects 83. (127/153) Continued Access 84.1% (58/69) TOTAL 83.3% COMBINED (185/222) AAA diameter decrease > 5mm 1 Pivotal subjects 16.3% (25/153) Continued Access 15.9% (11/69) TOTAL 16.2% COMBINED (36/222) 6 months 1 year 2 years 3 years 4 years X 2 X 2 X 2 X 2 X 2 1.3% (2/150) 1.5% (1/65) 1.4% (3/215) 66. (99/150) 67.7% (44/65) 66.5% (143/215) 3.8% (5/133) 8.7% (4/46) 5. (9/179) 55.6% (74/133) 39.1% (18/46) 51.4% (92/179) 11.5% (13/113) (0/4) 11.1% (13/117) 46. (52/113) 5 (2/4) 46.2% (54/117) 2 (4/20) 0/0 2 (4/20) 25% (5/20) 0/0 25% 5/ % (49/150) 40.6% (54/133) 42.5% (48/113) 55% (11/20) 30.8% 52.2% 5 (20/65) (24/46) (2/4) 0/0 32.1% 43.6% 42.7% 55% (69/215) (78/179) (50/117) (11/20) Data provided by imaging core lab Analysis windows are: 6 months (91 to 304 days), 1 year (305 to 547 days), 2 years (548 to 911 days), and 3 years (912 to 1277 days), and 4 years (1278 to 1642). 1 1-month imaging serves as the baseline measure. If 1-month imaging was missing the first available postoperative image served as the baseline measure. 2 Denominator at each time point is the number of subjects with at least one readable scan in the time interval. TriVascular conducted additional subset analyses of AAA diameter change to evaluate potential contributing factors: the analyses appear to show a correlation between subject geographic location and enlargement rates. In particular, the U.S. subjects had an aneurysm enlargement rate at 3 years of 5.6% (4/72), and the Germany subjects had an aneurysm enlargement rate at 3 years of 13. (3/23). The Chile subjects had an aneurysm enlargement rate at 3 years of 33.3% (6/18) (with a type II endoleak rate of 61.1% [11/18]). TriVascular is evaluating potential contributing factors for higher rates in certain geographies, including subject medical histories, concurrent medications, and anatomical factors. Stent Graft Migration The proportion of subjects with a device migration identified by the imaging core laboratory is at all reported time points for both the Pivotal cohort and the Continued Access group. The data for the de novo cohort is not yet available as the 1-month imaging mainly serves as the baseline, and the longest implant duration in this cohort is 43 days. Page 13 of 23

15 Patency Loss of device patency due to aortic body stenosis was identified by the site in 1 (0.7%) Pivotal subject at 6 months post-treatment and in 1 Continued Access subject (1.5%) at 1 year. Loss of device patency due to iliac limb occlusion was identified by the site in 1 (0.7%) Pivotal subject and in 1 (2.) Continued Access subject at 2 years post-treatment. The Pivotal cohort subject at 6 months was successfully treated with a stent, and the 2 year subject was successfully treated with thrombectomy and a stent. The Continued Access subject at 1 year was successfully treated with thrombectomy, and the Continued Access subject at 2 years was treated with a fem-fem bypass. Subjects that were treated between follow-up visits are described in the Secondary Endovascular Procedures section above. Table 8. Loss of Device Patency Loss of Device Patency Treatment to 12 months X 1 month X% (n/n) 6 months X 1 year X% (n/n) 2 years X% (n/n) 3 years X% (n/n) 4 years X Pivotal subjects 0.6% (1/160) (0/159) 0.7% (1/153) (0/151) 0.7% (1/135) (0/118) 3.8% (1/26) Continued 1.3% 1.5% 2. Access (1/77) (0/76) (0/70) (1/65) (1/49) (0/4) 0/0 De novo Cohort (0/11) (0/10) (0/1) 0/0 0/0 0/0 0/0 TOTAL COMBINED 0.8% (2/248) (0/245) 0.4% (1/224) 0.5% (1/216) 1.1% (2/184) (0/122) 3.8% (1/26) Data provided by site evaluation Analysis windows are: 1 month (1 to 90 days), 6 months (91 to 304 days), 1 year (305 to 547 days), 2 years (548 to 911 days), and 3 years (912 to 1277 days), and 4 years (1278 to 1642). Device Integrity Stent fractures were identified by the imaging core laboratory through 12 months post-treatment in 2.5% (6 of 236) of all subjects treated in both the Pivotal and Continued Access cohorts. There were no reports of loss of integrity (e.g. holes, tears) of the PTFE graft material. None of the stent fractures were associated with clinical sequelae, and none have required treatment. After a stent fracture is initially reported, it is then reported at each subsequent time period. The time to initial event notification is outlined in the following paragraphs. The time to initial event identification for the Pivotal cohort was 30 days (n=1), 6 months (n=1), 12 months (n=2), 2 years (n=1) and 3 years (n=5). One subject identified in the 12 month group died before the 2 year follow-up related to preexisting conditions (COPD and lung cancer) and not related to the device. As of the date of this analysis, not all subjects in the Pivotal cohort with stent fractures at 2 years have reached the 3 year follow-up window. Page 14 of 23

16 The time to initial event identification for the Continued Access cohort was 1 year (n=2) and 2 years (n=2). Table 9. Loss of Integrity Device Integrity Treatment to 12 months X 1,2 1 month X% (n/n) 1,2 6 months X% (n/n) 1,2 1 year X% (n/n) 1,2 2 years X 1,2 3 years X 1,2 4 years X% (n/n) 1,2 Pivotal subjects 2.5% (4/160) 0.6% (1/157) 1.3% (2/150) 2.7% (4/147) 3.3% (4/123) 6.6% (7/106) (0/19) Continued 2.6% 3.1% 8.7% Access (2/77) (0/77) (0/70) (2/64) (4/46) (0/2) 0/0 De novo 0/0 Cohort (0/10) (0/1) 0/0 0/0 0/0 0/0 TOTAL COMBINED 2.5% (6/236) 0.4% (1/244) 0.9% (2/221) 2.8% (6/211) 4.7% (8/169) 6.5% (7/108) (0/19) Data provided by imaging X-ray core lab for Pivotal and Continued Access Subjects. Data provided by the clinical site for de novo Subjects. Analysis windows are: 1month (1 to 90 days), 6 months (91 to 304 days), 1 year (305 to 547 days), 2 years (548 to 911 days), and 3 years (912 to 1277 days), and 4 years (1278 to 1642). 1 Denominator at each time point is the number of subjects with at least one readable scan in the time interval. Missing or unreadable 1 Month measures were imputed with available discharge X-ray measures. 2 Numerator is number of subjects with a stent fracture reported in the time interval. Once a stent fracture is reported it will also be reported at each subsequent time interval. Page 15 of 23

17 Section II: Worldwide Commercial Experience All complaints received by TriVascular related to the Ovation/Ovation Prime devices are reviewed, analyzed, and evaluated for changes to the risk analyses conducted for the product. To date, the complaint rates have remained at a low level and are consistent with the risk analysis. As of July 31, 2014, almost 20,000 units of the Ovation and Ovation Prime Abdominal Stent Graft devices (aortic body, iliac limb, iliac extension and fill polymer kit) have been sold worldwide (6140 total units in the United States and 13,164 total units outside of the United States). Table 10 below summarizes the worldwide events reported to TriVascular during that timeframe. Note that the table includes reported potential endoleaks, nearly 25% of which were not definitively confirmed to be type IA endoleaks but are conservatively included below. Additionally, only one (1) aneurysm-related death occurred after 30 days post-implant. Table 10: Summary of Ovation/Ovation Prime worldwide events Event Type United States (October 5, 2012 July 31, 2014) Outside the United States (August 17, 2010 July 31, 2014) Rupture 2 2 Aneurysm Enlargement 0 1 Conversion AUI Open Surgical Repair Migration 0 1 Endoleak Type IA Type IB Type III Device Occlusion Aortic Body Iliac Limb Device Integrity Stent Graft Aneurysm-related Death In late September 2014, TriVascular initiated a voluntary field safety corrective action (FSCA) related to 29 mm Ovation Prime aortic body stent grafts manufactured within a defined time period. Fewer than 30 devices were subject to the FSCA, all of which were held by distributors outside the United States (Canada and Europe). The FSCA was initiated due to an increase in complaints related to rapid emptying of the fill polymer syringe in 29 mm Ovation Prime aortic body stent grafts during the implant procedure, which could lead to incomplete aortic body graft fill, transient hypotension response, prolonged procedure time, and/or failure to exclude the aneurysm. In the related 29 mm Ovation Prime aortic body complaints, one procedure was prolonged, and most patients experienced transient hypotension (managed in accordance with the instructions for use) and aneurysm exclusion, although some of these patients had incomplete Page 16 of 23

18 filling of the graft. Two patients with incomplete filling of the graft did not have aneurysm exclusion at the end of the index procedure so the physicians were planning later interventions. There was no associated risk to patients with existing implanted Ovation Prime stent grafts, and all devices subject to the FSCA were returned to TriVascular and deployed in a non-clinical setting to render them non-implantable. During the root cause investigation, TriVascular identified that the rapid emptying of the fill polymer syringe was attributed to possible stent graft damage incurred during the loading process, which was addressed by replacement of tooling used during stent graft loading. The action was closed by FDA in December Page 17 of 23

19 Section III: Explant Analysis TriVascular has not received additional explants since the 2013 Annual Clinical Update. Therefore, the information within this section has been maintained from the previous report, which includes data from the period of September 2010 through July 31, As described in the 2013 Annual Clinical Update, TriVascular received 3 explanted devices from commercial cases outside of the U.S. Each of the explanted devices was evaluated by internal personnel and then assessed to evaluate device integrity and determine the reason for explant. One of the explants (device implanted for 34 days, surgical conversion) was explanted due to a type I endoleak, but the physician determined during the explant procedure that the patient had a type II endoleak. A second explant at 2 days post-implant (autopsy) occurred in a patient that had severe atherosclerotic disease of the access vessels and significant blood loss requiring transfusion. Poor imaging quality coincided with subsequent challenges with accurate placement of the device. The patient expired from myocardial infarction and multi-organ failure. A third explant (implanted for 0 days) was an intraoperative surgical conversion because of a type IA endoleak that was potentially caused by challenging aortic neck anatomy with significant calcification, in combination with incomplete apposition of the sealing ring with the aortic wall possibly due to graft placement location and/or not retracting the guidewire during graft fill. These conclusions were supported by analysis of the available clinical information, and there were no device integrity issues identified with the three examined devices. TriVascular will continue to evaluate explanted devices and summarize the information in future Clinical Updates. Section IV: Instructions for Use (IFU) Clarification In 2014, FDA approved clarified indications for use to include femoral cutdown or percutaneous in regards to vascular access techniques, which are supported by the existing clinical study data. Additionally, the aortic landing zone inner wall diameter requirement was revised to accurately describe device sizing in relation to the sealing ring technology. Figure 1 provides an image of the device with its sealing mechanism in the aorta. Page 18 of 23

20 Figure 1. TriVascular Ovation Prime Abdominal Stent Graft in aorta Because of the sealing ring technology, the sizing considerations are unique: the aortic inner diameter is measured at the intended proximal sealing ring location, which is 13mm below the inferior renal artery. The approved indications now state: The TriVascular Ovation Prime Abdominal Stent Graft System is indicated for treatment of patients with abdominal aortic aneurysms having the vascular morphology suitable for endovascular repair, including: Adequate iliac/femoral access compatible with vascular access techniques (femoral cutdown or percutaneous), devices, and/or accessories, Proximal aortic landing zone: - with an inner wall diameter of no less than 16 mm and no greater than 30 mm at 13 mm below the inferior renal artery, and - with an aortic angle of 60 degrees if proximal neck is 10 mm and 45 degrees if proximal neck is < 10 mm, Distal iliac landing zone: - with a length of at least 10 mm, and - with an inner wall diameter of no less than 8 mm and no greater than 20 mm. Section V: Summary and Conclusions The information in this summarizes the clinical data and commercial information for the. The worldwide commercial experience reflects the clinical study experience from both the Pivotal and Continued Access cohorts. Pivotal cohort patients are entering the 4 year follow-up Page 19 of 23

21 interval, and the available 4 year data remains consistent with the early Ovation clinical study experience (no ruptures, no surgical conversions, no migrations, low AAA-related mortality, low AAA-related secondary interventions, low rates of loss of device integrity, and low loss of patency rates). The low profile delivery system (14 F) combined with a robust aneurysm sealing technology offers an EVAR treatment option to a broader pool of patients. The combination of the clinical and commercial experience provides continued evidence that the device is safe and effective for treatment of AAA disease. Page 20 of 23

22 Section VI: Brief Summary of Indications, Contraindications, Warnings and Precautions from IFU Please also refer to the product instructions for use (IFU) at Indications for Use The TriVascular Ovation/Ovation Prime Abdominal Stent Graft Systems are indicated for treatment of patients with abdominal aortic aneurysms having the vascular morphology suitable for endovascular repair, including: Adequate iliac/femoral access compatible with vascular access techniques (femoral cutdown or percutaneous), devices, and/or accessories, Proximal aortic landing zone: -with an inner wall diameter of no less than 16 mm and no greater than 30 mm at 13 mm below the inferior renal artery, and -with an aortic angle of 60 degrees if proximal neck is 10 mm and 45 degrees if proximal neck is < 10 mm, Distal iliac landing zone: -with a length of at least 10 mm, and -with an inner wall diameter of no less than 8 mm and no greater than 20 mm. Contraindications Patients who have a condition that threatens to infect the graft. Patients with known sensitivities or allergies to the device materials (including polytetrafluoroethylene [PTFE], polyethylene glycol [PEG]-based polymers, fluorinated ethylene propylene [FEP] or nitinol). Warnings and Precautions General The Ovation/Ovation Prime Abdominal Stent Graft System is for single patient use only. Accurate fluoroscopic imaging is required during any endovascular procedure and for proper device deployment. Implantation of this device should occur in an operating room, endovascular suite, catheterization laboratory, or similar sterile environment, with appropriately trained personnel, and suitable equipment and imaging capabilities. Do not use this device if the patient is unable to be evaluated using the necessary preoperative and postoperative imaging. Always have a qualified surgery team available during implantation or re-intervention procedures in the event that conversion to open surgical repair is necessary. The devices should only be used by physicians and teams experienced in endovascular techniques and who have been trained in its use. The long-term performance of this implant has not been established. All patients treated with this device must undergo periodic imaging to evaluate stent graft integrity and position, aneurysm size, and potential endoleaks and/or occlusion of vessels in the treatment area. Significant aneurysm enlargement, a persistent endoleak, the appearance of a new endoleak, device migration, reduced blood flow through the graft, and/or decrease in renal function due to renal artery occlusion should prompt further investigation into the need for further patient treatment, including additional intervention or surgical conversion. Additional patient imaging follow up should be considered for patients with devices that have effectiveness issues. All patients should be carefully counseled on the need for long-term follow up. The device is not recommended in patients unable or unwilling to comply with the information in Follow-up Imaging Recommendations. Page 21 of 23

23 Patient and Device Selection Access vessel diameter, vessel morphology and delivery system diameter should be compatible with vascular access techniques (femoral cutdown or percutaneous). Vessels that are significantly calcified, occlusive, tortuous or thrombus-lined may preclude placement of the device. The Ovation/Ovation Prime Abdominal Stent Graft Systems have not been evaluated in patients who: o Are pregnant or nursing; o Are less than 18 years old; o Have traumatic aortic injury, ruptured aneurysms, aneurysms pending rupture or require other emergent aorta/ aneurysm treatment; o Have suprarenal, thoraco-abdominal, ilio-femoral, juxtarenal, pararenal, mycotic, inflammatory, dissecting or pseudo-aneurysms; o Have hypercoagulability, bleeding diathesis or coagulopathy; o Have mesenteric and/or celiac artery occlusive disease and a dominant patent inferior mesenteric artery; o Have connective tissue disorder or congenital degenerative collagen disease, e.g., Marfan s or Ehler s-danlos Syndrome; o Require bilateral exclusion of hypogastric blood flow; o o Have baseline serum creatinine level of > 2.0 mg/dl; Have other medical, social or psychological conditions that preclude them from receiving the pretreatment, required treatment, and post-treatment procedures and evaluations. Irregular calcification and/or plaque may compromise the fixation and/or sealing at the implantation sites. Key anatomic elements that may affect exclusion of the aneurysm include severe proximal neck angulation (> 60), distal iliac landing zone < 10 mm, and/or aortic neck/iliac inner wall diameter inappropriately sized to the stent graft. Inappropriate patient selection may result in poor device performance. This device is not recommended in patients who: have or are suspected of having an active systemic infection; cannot tolerate contrast agents necessary for intra-operative and post-operative follow up imaging; and/or have sensitivities or allergies to the stent graft system materials, antiplatelets or anticoagulants; have unstable angina and/or myocardial infarction (MI) or cerebral vascular accident (CVA) within 6 months prior to implantation; exceed weight and/or size limits necessary to meet imaging requirements. Implant Procedure Pre-operative planning for access and placement should be performed before opening the device packaging. Studies indicate that the danger of micro-embolization increases with increased procedure duration. Renal complications may occur from an excess use of contrast agents and/or as a result of an embolic or misplaced stent graft. Carefully inspect the device packaging and device for damage or defects prior to use. If signs of damage or defects exist or if premature breach of the sterile barrier is observed, do not use the device. Minimize handling of the stent graft constrained on the delivery catheter during preparation and insertion to decrease the risk of contamination and infection. Do not resterilize any components of the device. Systemic anticoagulation should be used during the implantation procedure based on hospital and physician preferred protocol. If heparin is contraindicated, an alternative anticoagulant should be considered. Do not excessively bend or kink the device because it may damage the device and/or its components. Always use fluoroscopic guidance to advance the delivery system and to monitor the implant procedure, the device deployment and the fill polymer injection / cure. Exercise care in handling and delivery techniques to help prevent vessel rupture. Exercise particular care in difficult areas, such as areas of stenosis, intravascular thrombosis, or in calcified or tortuous vessels. If the iliac delivery system graft cover is accidentally withdrawn, the device will prematurely deploy and may be incorrectly positioned. Inaccurate placement or inadequate seal may result in increased risk of endoleak into the aneurysm. Page 22 of 23

24 Do not continue advancing any portion of the delivery system if resistance is felt during advancement of procedure accessories or of stent graft system. Exercise particular care in areas of stenosis, intravascular thrombosis, or in calcified or tortuous vessels. Unless medically indicated, do not deploy the stent graft components in a location that will occlude arteries necessary to supply blood flow to organs or extremities or result in an endoleak. Stent graft components cannot be replaced or drawn back into the delivery system, even if the stent graft component is only partially deployed. Inadvertent partial deployment or migration of the stent graft may require surgical removal or repair. Do not push or pull the delivery system after complete deployment of the proximal stent to avoid inadvertent disconnection of the polymer fill connector from the implant. During device use, rotate entire delivery system as a unit. Do not independently rotate catheter sheath or handle. Inadequate seal zone may result in increased risk of endoleak into the aneurysm. Ensure an extra stiff wire is not inside the aortic body during injection of the fill polymer to allow conformance of the stent graft to the native anatomy when significant angulation is present. Use only the Autoinjector to fill the Aortic Body Stent Graft. Hand injection should not be used and may damage the implant. Confirm there is no tension on the aortic body stent graft prior to or during iliac limb or iliac extension placement to prevent possible stenosis or occlusion. Confirm cannulation of aortic body contralateral lumen to ensure accurate placement of the contralateral limb. It is important to accurately size and choose the balloons to be used during device deployment. Keep the balloon inside the graft during inflation and do not over-inflate within the stent graft. Although not observed during the Ovation clinical study, inflation of the balloon outside of the graft may lead to vessel damage or rupture. Carefully follow the balloon manufacturer s inflation parameters described in the product labeling. Any endoleak left untreated during the implantation procedure must be carefully monitored after implantation. Patients who experience hypersensitivity reactions during the procedure should be managed in accordance with standard recommendations for treatment of patients with radiocontrast agent allergies (e.g., antihistamines, corticosteroids, adrenaline). MRI Information Non-clinical testing has demonstrated that the device is MR Conditional. It can be scanned safely in both 1.5T and 3.0T MR systems using the specific testing parameters listed in the IFU under Section 10.4, MRI Information. Page 23 of 23

25 3910 Brickway Boulevard Santa Rosa, CA USA trivascular.com CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician TriVascular, Inc. All rights reserved rc