EVAS - Building the clinical evidence Paul Hayes Vascular Surgeon Cambridge University January, 2016

What do we know about EVAR?

Schanzer et al. Circulation. 2011; 123(24):2848-55. 2

Complications are twice as common with Type 2 EL

Event Type II EL No Type II EL

Aneurysm Sac Enlargement 40% 17%

Secondary Intervention 15% 7%

Rupture 2% 1%

Conversion 6% 3%

Type II Endoleak DOUBLES complications following EVAR

Secondary Interventions Increase Costs

“Efforts aimed at minimizing cost should emphasize technical and device modifications aimed at reducing endoleaks and the need for secondary procedures.”

Event No Yes

Endoleak $5,706 $26,739

Secondary Intervention $3,668 $31,696

Noll RE, et al. J Vasc Surg 2007

EndoVascular Aneurysm Sealing (EVAS) with Nellix

Designed to seal entire aneurysm

Expands endovascular patient eligibility

May overcome issues associated with conventional endografts

Rapidly growing evidence base

6

Pubmed

references

2011 2

2012 1

2013 2

2014 6

2015 30

7

Topic No. Publications

Technology Overview 6 Boeckler, Zentral Chir 2014; Buckley, Semin Vasc Surg 2012; Donayre, Endovasc Today 2009; Holden, Cardiovasc Intervent Radiol, 2014; Holden, J Cardiovasc Surg 2015; van den Ham, Surg Technol Int 2015

EVAS Applicability 1 Karthikesalingam, Eur J Vasc Endovasc Surg 2013

Clinical Outcomes (Gen 1, 2)

3 Donayre, J Vasc Surg 2011; Krievins, Eur J Vas Endovasc Surg 2011; Kisis, Medicina (Kaunas) 2012

Clinical Outcomes (Gen 3)

8 Carpenter, J Vasc Surg 2015; Holden, J Cardiovasc Surg 2015; Alsac, Ann Vasc Surg 2015; Boeckler, J Vasc Surg 2015; Brownrigg, Eur J Vasc Endovasc Surg 2015; Gossetti, J Cardiovasc Surg 2015; Szopinski, Eur J Vasc Endovasc Surg 2015, Zerwes, Vascular 2015

Quality of Life 1 Kisis et al, Medicina (Kaunas) 2012

Imaging Surveillance 5 Holden, J Endovasc Ther 2015; D’Abate, J Endovasc Ther 2015; Karthikesalingam, Endovasc Ther 2015; McWilliams, Endovasc Ther 2015; Ezite, Acta Chir Lat 2013;

Endoleak Management 3 Brownrigg, Eur J Vasc Endovasc Surg 2015; Harvey, JVIR 2016 (accepted); Ameli-Renani, Cardiovasc Intervent Radiol 2015

Iliac Aneurysm 2 Ter Mors, J Endovasc Ther 2015; Krievins, Eur J Vasc Endovasc Ther 2015

Morphology 3 Savlovskis, J Vasc Surg 2015; Boersen, Eur J Vasc Endovasc Surg 2015; Shaikh, J Endovasc Ther 2015

Infection 2 Ferrero, Ann Vasc Surg 2015; Tolenaar, J Endovasc Ther 2015

ChEVAS 9 Boeckler, J Cardiovasc Surg 2014; Dijkstra, J Endovasc Ther 2014; Malkawi, J Endovasc Ther 2014; Niepoth, J Endovasc Ther 2014; Rouer, Ann Vasc Surg 2014; Truijers, J Endovasc Ther 2015; Torella, Cardiovasc Intervent Radiol 2015; Malaj, Ann Vasc Surg 2015; Youssef, JCTS 2016

rEVAS 6 Reijnen, J Endovasc Ther 2015; Truijers, J Endovasc Ther 2015; DeBruin, J Endovasc Ther 2015; Antoniou, J Endovasc Ther 2015; Coppi, J Vasc Interv Radiol 2015; Boeckler, J Cardiovasc Surg 2014

EVAR Revision 3 Van den Ham, J Endovasc Ther 2015; Hughes, J Endovasc Ther 2015; Boeckler, J Cardiovasc Surg 2014

VALIDATING EVAS: Nearly 50 peer-reviewed publications

TREAT MORE PATIENTS

73% 68%

52%

29%

27% 32%

48%

71%

0%

20%

40%

60%

80%

100%

Nellix Medtronic Endurant Zenith Flex Gore Excluder

% Compliant % Not Compliant

Karthikesalingam A, et al. Eur J Vasc Endovasc Surg 2013

More Patients can be Treated On-IFU with Nellix Nellix Suitability Analysis among 776 patients treated previously with other modality

Authors Published Study N Follow-Up

Carpenter et al J Vasc Surg 2015 150 30d

Holden et al (Presented) Veith 2015 277 1yr

Multiple, Physician-Initiated, Real-World Observational Studies

Boeckler et al J Vasc Surg 2015 “Early Nellix Learnings”

Retrospective Review from 7 Centers Treated Oct 2012 through Mar 2014 (before Global Registry)

171 5 mo

Brownrigg et al Eur J Vasc Endovasc

Surg 2015

St. George’s Experience (UK) Largest enrolling site in EVAS Global Registry

Professors Matt Thompson and Ian Loftus 105 30 days

Holden J Cardiovasc Surg

2015 New Zealand, Single Center Study

Professor Andrew Holden, early EVAS pioneer 120 14 mo

Alsac et al Ann Vasc Surg

2015 French, Single Center Study

Prospective Study 20 30d – 1yr

Gossetti et al J Cardiovasc Surg

2015 Italian, Single Center Study 24 30d – 1yr

Szopinski et al Eur J Vasc Endovasc

Surg 2015 Polish, Single Center Study 50 30d – 1yr

Zerwes et al Vascular 2015 German, Single Center Study 50 3 mo

VALIDATING EVAS: Building a Broad Base of Evidence

CONFIDENTIAL

30 Day Results

Carpenter et al, J Vasc Surg 2015

• US IDE Pivotal Trial

• National PI: Jeff Carpenter

• 150 patients at 29 sites: US (26) EU (3)

• Enrollment completed Nov 2014

• Continued access underway

• 30d results presented at SVS 2015

• 1 year results expected Q2 2016

CONFIDENTIAL

Baseline characteristics

Characteristic Mean ± SD (range)

Maximum sac diameter 57.5 ± 6.2 (44, 82)

Non-aneurysmal neck length 31.2 ± 14.0 (10, 103)

Max neck diameter 25.2 ± 3.0 (19, 32)

Aortic Neck Angulation (◦) 29.9 ± 14.2 (3, 59)

CONFIDENTIAL

Procedural data

Parameter Result (N=150)

Device Implant Time 30 min

Fluoroscopy Time 10 min

Total Procedure Time 87 min

Anesthesia Time 187 min

Polymer Fill Volume 75 mL

Time to Hospital Discharge 1.2 days

Results shown as median

CONFIDENTIAL

30 Day Results

100% procedural technical success

Low aneurysm-related mortality (0.7%) and MAEs (2.7%)

No Ruptures, No Conversions

Low incidence of any endoleak

5% Type II - 0.1-0.4 mL (all lumbar); no sac expansion or reintervention

One Type 1a, successfully treated (0.7%)

No Occlusions or Thrombosis

No Device Integrity Issues

Type 2 leak in the IDE trial

14

1yr 30d 6mo

Type 2 Endoleak Resolve with no Sac Expansion or Clinical Sequalae

Device* N MAE 30d Death Endoleaks Secondary

Interventions

Zenith 299 na 1.0% 11% nr

Excluder 235 na 1.3% 22% nr

Endurant 150 4.0% 0% 16% 3.3%

Ovation 161 2.5% 0.6% 44% 1.2%

Aorfix 218 na 1.8% 19% nr

Nellix† 150 2.7% 0.7% 6.0% 0.7%

CONFIDENTIAL

30 Day IDE Comparisons

*30d results for commercially available devices shown per the respective US FDA Summary of Safety and Effectiveness Data (SSED) and peer-reviewed publications of trial results.

na: not applicable. This definition of MAE is different than that of other studies shown. nr: not reported

• Sac size should remain stable or shrink with time

• Shrinkage due to resorption of mural thrombus

• Once mural thrombus has resorbed, no further shrinkage is possible

Surveillance Appearances

Sac Shrinkage noted in 80% cases (n=24) Gossetti et al, JCVS 2015

Pre-op 1mo 6mo 1yr 2yr

EVAS DURABILITY and SAC STABILITY

Sac Stability thru 2 years Courtesy of J Savlovskis, D Krievins

Authors Modalities / Topics

Holden et al Nellix Advisory Board J Endovasc Ther 2015

A Consensus Document CT, US, MR

D’Abate et al St. George’s (UK)

J Endovasc Ther 2015

Ultrasound

Karthikesalingam et al St. George’s (UK)

J Endovasc Ther 2015

CT

McWilliams et al Liverpool, UK

J Endovasc Ther 2015

CT and Ultrasound

Brownrigg et al Eur J Vasc Endovasc Surg 2015

30d Outcomes in 1st 105 patients Includes case example of successful transcatheter

embolization of Type 1a endoleak

IMAGING SURVEILLANCE and ENDOLEAK MANAGEMENT

Lowest ever-reported endoleak rates at 1 year compared to EVAR IDEs

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

EVAS Zenith IDE Endurant IDE Aorfix IDE Excluder IDE Incraft CE Ovation IDE

Type IA, IB Type II Type III/IV Undetermined

0.7%

7.4% 9.8%

17% 17%

37% 39%

*1 Yr results for commercially available devices shown per the respective US FDA Summary of Safety and Effectiveness Data (SSED) and peer-reviewed publications of trial results.

Holden et al, Veith Symposium 2015

Thank you