HeartWare ADVANCE Bridge to Transplant Trial and Continued Access Protocol Update

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Susanna Tucker
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1 HeartWare ADVANCE Bridge to Transplant Trial and Continued Access Protocol Update Mark S. Slaughter, MD University of Louisville, KY, USA HeartWare Users Meeting 29 October 2012 Barcelona, Spain HEARTWARE, HVAD and the HEARTWARE logo are registered trademarks of HeartWare, Inc HeartWare, Inc.

design, continuous flow Hybrid magnetic / hydrodynamic impeller suspension Optimizes flow,

2 HeartWare Ventricular Assist System HVAD miniaturized implantable blood pump o o o o o Pericardial placement no pump pocket Provides up to 10 litres/min of flow Centrifugal design, continuous flow Hybrid magnetic / hydrodynamic impeller suspension Optimizes flow, pump surface washing, and hemocompatibility Thin (4.2 mm), flexible driveline with fatigue resistant cables

3 The HVAD System Surgical Implant No abdominal surgery No pump pocket Potential to expand treatable patients Potential for short implant time Could reduce blood loss Accurate flow estimation Log files enable flow and power waveform analysis

4 International New Sites/New Markets Over 2500 implants WW Expanding global acceptance o 100 customers, 26 countries o 276 units sold in Q2; 80% Int l growth o 500 units H1 Building momentum 26 new centers in 2012

5 Study Design Objective: To evaluate safety & efficacy of HVAD in patients listed for cardiac transplantation with refractory, advanced heart failure Multi-center, prospective, non-randomized, two arm study HVAD (N=140) vs. Control (INTERMACS, N=499) Primary endpoint: Non-inferiority to control Secondary endpoints: Descriptive statistics First BTT using contemporaneous VAD patients as control arm (INTERMACS registry) Primary Endpoint: Success at 180 days alive on original device, transplanted, or explanted for recovery (alive 60 days post removal) Failure at 180 days death, device exchange, or death after explantation (prior to 60 days)

6 Study Milestones Patient enrollment: August 2008 February 2010 Study cohort follow-up completed August 2010 PMA filed December 2010 Favorable FDA Panel recommendation April 25, 2012 BTT CAP initiated April 2010 Three CAP allotments completed (54, 54, 94) Fourth CAP allotment granted March 2012 ongoing (1 slot remains)

7 Patient Demographics Baseline Characteristic BTT and CAP (N = 332) BTT (N = 140) CAP (N = 192) Age (years) 52.8 ± ± ± 12.9 Male sex (%) 71.1% 72.1% 70.3% Race (%) White Black/African American Hispanic/Other 68.7% 25.9% 5.4% 72.1% 22.9% 5.0% 66.1% 28.1% 5.7% Body-mass index (kg/m 2 ) ± ± ± 6.2 Body surface area (m 2 ) 2.0 ± ± ± 0.3 Ischemic cause of heart failure (%) 36.7% 40.7% 33.9% Left ventricular ejection fraction (%) 17.4 ± ± ± 7.6

8 Patient Demographics (cont.) Baseline Characteristic BTT and CAP (N = 332) BTT (N = 140) CAP (N = 192) Pulmonary artery pressure (mmhg) Arterial blood pressure (mmhg) Cardiac index (liters/min/m 2 ) NYHA Class (%) Systolic Diastolic Systolic Diastolic Mean II III IV NA INTERMACS (%) ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±

9 Overall Kaplan-Meier Survival (N=332) Survival: 180 days = 91% 360 days = 84% * Data as of 07/30/12

10 Competing Outcomes (N=332) * Data as of 07/30/12

11 Summary of Adverse Events Bleeding N=332 Requiring re-op % Patients Affected (n) 14.8% (49) Number of events Event Rate (PPY) (PY=305.9) Gastrointestinal 12.7% (42) Infections Driveline exit site 16.9% (56) Sepsis 17.2% (57) Arrhythmia Ventricular 20.8% (69) Supraventricular 21.4% (71) Renal dysfunction 9.6% (32) Hepatic dysfunction 4.8% (16) Respiratory dysfunction 22.0% (73) * Data as of 07/30/12

12 Summary of Adverse Events (cont.) N=332 % Patients Affected (n) Number of events Event Rate (PPY) (PY=305.9) Device exchanges Procedure-related 2.1% (7) Suspected thrombus 4.2% (14) Other 2.4% (8) Neurological events Ischemic CVA 7.5% (25) Hemorrhagic CVA 7.8% (26) TIA 4.8% (16) Right heart failure Inotropic therapy 25.0% (83) RVAD Inhaled NO 3.3% (11) 1.2% (4) Venous thromboembolism 6.3% (21) Arterial embolism 1.5% (5) * Data as of 07/30/12

13 VAD Thrombus: Greatly Reduced by Medical Intervention and Device Design Reduction in thrombus events has occurred across ALL trials: a) Improved anticoagulation b) Improved coring tool the adjustment (began c) Sintered pump inflow ) d) User experience Most cases of VAD thrombus occur with non-sintered pumps. Most often, patients have INRs < 2 and ASA at 81 mg/day. The era of intraventricular tpa is over; peripheral tpa works very well. Most patients detected early can be managed medically.

14 Device Exchange for Suspected Pump Thrombus Pre-Adjustment: Implants before March 15, 2011 Post-Adjustment: March 15, 2011-July 30, 2012 * Data as of 07/30/12

15 Incidence of Strokes: Effects of Improved Anticoagulation and Design Enhancements BTT + CAP (N=332) All ICVAs ICVAs with MRS > 0 % Patients with event BEFORE 6.3% (16/253) 5.1% (13/253) % Patients with event AFTER* 4.7% (10/211) 2.8% (6/211) BTT + CAP (N=332) All HCVAs HCVAs with MRS > 0 % Patients with event BEFORE 5.1% (13/253) 5.1% (13/253) % Patients with event AFTER* 6.6% (14/211) 4.7% (10/211) Strict adherence to anticoagulation guidelines and the introduction of an enhanced coring tool and sintered inflow cannula resulted in a reduction in ischemic and hemorrhagic strokes and enhanced full recovery (i.e. strokes with an MRS = 0). * A patient may be counted twice if they have more than one event which cross time periods.

16 HVAD Survival vs. Projected Survival % 96% 94% 80 83% 86% Observed Survival (%) % 59% 45% 76% 20 0 HVAD Advance SHFM Medical Therapy HVAD CAP * BTT Europe and Australia Years 29% Seattle Heart Failure Model per Professor Wayne Levy of the University of Washington. * CAP cohort has insufficient follow-up beyond 1 year (only 9 patients at-risk at year 2). * Data as of 09/05/12

17 Summary Overall 180 day survival in ADVANCE and CAP was 91.3%. Only 21% of the patients were transplanted by 180 days. Reoperations for bleeding, gastrointestinal bleeding, sepsis and driveline infections remain low. Mitigations to reduce pump thrombus have been highly successful. Similarly, the incidence of ischemic and hemorrhagic strokes is showing decline and full recovery (strokes with MRS = 0) is increasing.

Destination Therapy SO MUCH DATA IN SUCH A SMALL DEVICE. HeartWare HVAD System The ONLY intrapericardial VAD approved for DT.

DT Destination Therapy SO MUCH DATA IN SUCH A SMALL DEVICE. HeartWare HVAD System The ONLY intrapericardial VAD approved for DT. ONLY WE HAVE THIS BREADTH OF CLINICAL EVIDENCE TO SUPPORT DESTINATION THERAPY.