HeartWare Ventricular Assist System meets primary endpoint in ENDURANCE clinical trial

HeartWare International, Inc. (NASDAQ: HTWR), a leading innovator of less invasive, miniaturized circulatory support technologies that are revolutionizing the treatment of advanced heart failure, today announced that data from its first destination therapy clinical trial cohort, ENDURANCE, successfully demonstrated that the trial achieved the primary endpoint.

Results from HeartWare's ENDURANCE clinical trial were presented today during the Opening Plenary Session at the 35^th International Society for Heart and Lung Transplantation (ISHLT) Annual Meeting in Nice, France.

HeartWare's ENDURANCE clinical trial is a prospective, randomized, controlled, un-blinded Investigational Device Exemption (IDE) study designed to evaluate the HeartWare^® Ventricular Assist System as a destination therapy - or long-term therapy - for patients with end-stage heart failure who are ineligible for heart transplantation. Between August 2010 and May 2012, 446 patients were enrolled at 48 U.S. hospital centers and were randomly selected to receive either the HeartWare Ventricular Assist System or, as part of a control group, any alternative Left Ventricular Assist Device (LVAD) approved by the U.S. Food and Drug Administration (FDA) for Destination Therapy, in a 2:1 ratio.

Investigators for the study today reported that 55.0% of the investigational device patients attained the primary endpoint of the trial, which is stroke-free survival (Modified Rankin Score ≥4) at two years, defined as alive on the originally-implanted device, transplanted or explanted due to patient recovery. In comparison, 57.4% of patients in the control arm achieved the primary endpoint of the study. Based on these results for the primary endpoint of the ENDURANCE study, non-inferiority of the investigational device was established (p=0.0060).

"As the largest, randomized, destination therapy trial to date involving ventricular assist devices, the observations from ENDURANCE demonstrate the potential of the HeartWare System as a longer term treatment option for advanced heart failure patients who have exhausted medical therapy and are ineligible for a heart transplant," said Francis D. Pagani, M.D., Ph.D., a co-principal investigator for ENDURANCE, surgical director of the Adult Heart Transplant Program and director of the Center for Circulatory Support at the University of Michigan Health System. "Survival with the HVAD Pump at two years was comparable to the control device. HVAD device and design improvements, including sintering of the inflow cannula, resulted in improvements in outcomes, including a marked reduction in pump thrombosis."

Among the 200 patients who received the investigational device with a sintered inflow cannula, an enhancement granted by FDA in April 2011, 57.5% attained the primary endpoint.

Today, the HeartWare System, featuring the HVAD^® Pump, is only available with the enhanced sintered inflow. Sintering titanium is a process by which minute beads are metallurgically affixed to a titanium surface and is commonly used in medical devices to facilitate tissue adhesion at the sintered region. Sintering of the HVAD Pump on the outer surface of the implanted inflow tube is designed to promote tissue ingrowth on the lower section of the inflow tube.

Secondary endpoints for ENDURANCE include adverse events such as bleeding and infection, as well as functional status, assessment of neuro-cognitive function and patient quality of life.

"Treatment with the investigational device was associated with improvements in quality of life, NYHA functional classification, and sustained improvement in the six-minute walk distance of more than 90 meters," said Joseph Rogers, M.D., senior vice chief for clinical affairs, Division of Cardiology and Mechanical Circulatory Support Program at Duke University, and a co-principal investigator for ENDURANCE. "The observed stroke rate was higher in the investigational device arm, whereas device malfunctions leading to exchange or urgent transplant were more frequent in the control group. Multivariate analysis confirmed the previously-observed link between neurological events and mean arterial pressure, as elevated blood pressure was the strongest predictor of neurologic events."

"The breadth of clinical and commercial data presented at ISHLT is extensive. We are grateful for the leadership of our investigators and the commitment of our site coordinators for ENDURANCE, as well as the dozens of other leading heart failure surgeons and cardiologists who continue to conduct research and help us pursue opportunities to optimize outcomes for patients," said Doug Godshall, President and CEO at HeartWare. "Attaining the primary endpoint in this first cohort is encouraging, yet we view it as our core mission to continually improve patient outcomes with the HeartWare System. Just as we made enhancements to the device and implant procedure during the ENDURANCE enrollment period of 2010 to 2012, we are similarly making improvements to patient management and look forward to confirming the benefits of more consistent blood pressure monitoring in the second cohort of our destination therapy trial which is nearing full enrollment."

Enrollment in Second Cohort for Destination Therapy Nearing Completion
In the second destination therapy cohort, HeartWare is enrolling up to 310 HVAD patients, as well as up to 155 control patients, in a 2:1 randomization at 50 centers. The trial protocol approved by FDA was designed to confirm observations from ENDURANCE, that sites adhering to more regular monitoring and management of patient blood pressure witnessed a notably lower incidence of neurological events. The primary endpoint in the supplemental arm of the study is change in stroke incidence at 12 months on the originally-implanted device.

Enrollment for the destination therapy supplemental cohort commenced in October 2013, and with more than 80% of the study enrolled, HeartWare expects enrollment to be completed in mid-2015. The company intends to incorporate data from this second cohort into a Pre-Market Approval (PMA) application, which HeartWare anticipates submitting to FDA next year, seeking approval of the HeartWare System for the Destination Therapy indication.