FDA Panel Gives Cautious Nod to HeartWare’s LVAD Device

A U.S. Food and Drug Administration (FDA) advisory panel voted on April 25 to recommend the approval of the Ventricular Assist System from HeartWare International Inc.

The agency’s Circulatory System Devices panel voted 9-2 to recommend approval of the company’s experimental left ventricular assist device (LVAD) as a bridge to heart transplantation for patients with end-stage heart failure. The 11-member panel agreed unanimously that the new device is effective. The group wasn’t as harmonious about the device’s safety, but voted 8-3 that the device was safe.

Heart failure is a progressive disease that strikes one in five Americans older than 40. It occurs when a damaged organ can’t supply enough oxygen-rich blood to keep other organs, such as the lungs, working. There are few treatments and no cure.

Prior to the panel meeting, the FDA issued a report noting that though some questions remained about missing data for patients that tested the system, the device “seems to have statistically met the primary” FDA staff also expressed concern about stroke rates, according to agency documents. Fifteen patients on the HeartWare device experienced clotting and stroke about six months into testing, according to the FDA’s report. Agency staff said this suggests a trend toward higher stroke rates with the pump compared to other devices. If the device is approved, HeartWare most likely will have to conduct a post-approval study on the safety and effectiveness of the device by body surface area and quality of life five years after the date of implant. An agency representative told the panel the FDA was interested in a “rigorous” post-approval data.

HeartWare’s device currently is sold in Europe.

Of the nearly 140 patients who used HeartWare’s device in the final-phase trial (called ADVANCE), 90.7 percent survived, according to the company. This is compared with 90.1 percent of 499 patients in a registry for patients who use mechanical circulatory support for advanced heart failure, such as the HeartMate II, made by Pleasanton, Calif.-based Thoratec Corp. This is the first LVAD trial to use a registry as a control arm—an FDA first.  The primary endpoint of the trial was being alive after 180 days, or receiving a transplant. Panelists struggled with determining what sort of safety comparisons could be made between the HeartWare and registry arms of the trial—particularly when comparing stroke rates between HeartWare patients and the control group. The HeartMate II VAS is surgically implanted in an abdominal pouch, and the HeartWare VAS is implanted next to the heart.

Eleven patients who received the HeartWare device had an ischemic stroke within 180 days (27 percent of whom died or else were no longer eligible for a heart transplant) and four patients died of a hemorrhagic stroke. But whether 11 ischemic strokes is a high or low number is unclear, because stroke data wasn’t tracked in the registry. One panelist suggested 11 strokes are not a lot, especially given the alternative of not getting an LVAD, which for most patients would mean death. There were six deaths in the HeartWare group, three of which appeared to be related directly to the device. Still, the death rate was lower in the HeartWare group than in the registry group (4.3 percent compared to 8.8 percent).

Despite gaps in safety data, panelists seem to feel that another bridge-to-transplant LVAD option should be available for critically ill patients.

“I think this device is of incredible benefit to patients who are very ill,” said panelist Ralph Brindis, M.D., a cardiologist at Oakland Kaiser Medical Center in Oakland, Calif.

The U.S. market for left ventricular pumps may pass $750 million in 2015, Jason Mills, an analyst with Canaccord Adams Inc. in San Francisco, Calif., told Bloomberg news. Mills said if HeartWare’s product is approved for heart-failure patients who aren’t eligible for a transplant, the company may split the U.S. market with HeartMate II within the next three years.  Thoratec currently dominates the worldwide ventricular assist device market with about 68 percent of the market share, according to data compiled by a Bloomberg analyst, Michael Manns. HeartMate had $366 million in revenue last year.

HeartWare currently is recruiting patients for a study on the device’s use in patients who aren’t eligible for heart transplant, according to the National Institutes of Health website clinicaltrials.gov.

Acting panel chair, Richard Page, M.D., professor at the University of Wisconsin School of Medicine and Public Health called the HeartWare device “a real advance in technology” but said the ADVANCE trial was poorly conducted—“a mess,” he called it.

“We are pleased with the panel’s strong recommendation and would like to thank them for their thoughtful review of the data presented from the ADVANCE study,” said Doug Godshall, CEO and president of Framingham, Mass.-based HeartWare. “The Advisory Committee meeting outcome represents an important step toward approval of the HeartWare Ventricular Assist System in the United States, and we look forward to continuing our dialogue with the FDA as it finalizes its review of our PMA. HeartWare remains committed to optimizing outcomes for patients with end-stage heart failure and looks forward to expanding the clinical experience for the device in the future.”

Danielle Antalffy, an analyst with Boston, Mass.-based Leerink Swann, predicted in a note that FDA approval could be delayed to late fourth quarter of 2012 while the agency pursues more info on a lack of data with the sintered HVAD, which is the small implantable centrifugal blood pump called at the center of the HeartWare device. 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 in-growth on the lower section of the inflow tube. More time will allow increased data to be available from ongoing continued access protocol patient enrollment. Antalffy and colleagues previously had predicted a third-quarter approval.

The FDA is not bound by its advisory panel recommendations, but it usually follows them.