Medical Device Daily Washington Editor

GAITHERSBURG, Maryland – Friday’s meeting of the circulatory systems advisory panel of the FDA was replete with the usual debates over device safety and efficacy and featured some real-life data in the form of three patients implanted with the HeartMate II (HMII), the newest generation of the HeartMate left ventricular assist device (LVAD) made by Thoratec (Pleasanton, California).

While it is unlikely that panelists were particularly impressed by the testimony of these patients, they represented the dire condition of many with heart failure. And the need to help such patients may have ushered the device to an approvable recommendation – with conditions – despite the failure of the device to hit pivotal trial performance benchmarks.

The patients were two women, appearing to be in their 30s or younger, both schoolteachers; and a man looking to be in his 70s. And perhaps the most compelling comment came from one of the teachers, Salina Gonzalez, who testified that the HMII “was my only hope of life — to get one more chance to watch my son grow up.”

Don Middlebrook, Thoratec’s VP for regulatory affairs, told the panel that following FDA approval of the pivotal study for the HMII in February 2005 the company completed enrollment of the agreed-upon total of 133 patients in May 2006, calling this “a record pace of enrollment in the history of this technology.”

He noted that in April 2007, FDA sent a major deficiency letter to Thoratec regarding the trial, and that Thoratec had implanted the device in another 280 patients in a continuous access program (CAP).

Thoratec presented all the data both to FDA and to the panel in support of its application, but the panel was more focused on the pivotal trial data, with the device missing the prescribed objective performance criteria by one percentage point.

Middlebrook also described a proposed post-approval study (PAS), a “comprehensive plan” that would make use of the Interagency Registry of Mechanically Assisted Circulatory Support (Intermacs) registry, sponsored by the FDA, CMS and the National Heart, Lung and Blood Institute of the National Institutes of Health.

Leslie Miller, MD, chief of cardiology at Washington Hospital Center (Washington), the study’s principal investigator, said that although 29 of the 133 original enrollees passed away during the study, most of the patients who were on the device for 180 days saw significant improvement in functional status.

An assessment of New York Heart Association heart failure status showed that “all patients were class IV at enrollment,” but after six months, “nearly all the patients had achieved a class I or II functional capacity,” Miller said, a finding that he said was confirmed by the other two data groups.

One of these groups was the CAP population; the other was a group of 15 patients whose body surface area (BSA) was smaller than the area specified in the study protocol and hence analyzed separately (seven of the small-BSA patients were originally enrolled in the pivotal study, bringing down the numbers for that study to 126).

Still, the fact that most of the small-BSA subjects were women piqued panel interest, due to the fact that the most recent generation of the HeartMate is of little use in many patients of smaller stature.

However, the panelists also noted that height is only a surrogate of the volume of space within the rib cage. Rib cage volume, they said, may be a better marker of ability to handle the XVE, the vented electrical model that is the most recent of Thoratec’s approved LVADs. But this too is notoriously difficult to measure due to the need to adjust for the differential measure of torso volume imposed by overlaying adipose tissue.

Due to the small numbers concerning the women, these data were not the subject of much scrutiny by the panel despite the great interest in this population.

Bleeding events were the focus of much of the meeting, with 59 of the adverse events reported consisting of hemorrhage (the FDA data did not indicate whether these 59 events represented exactly 59 patients), a level that some panelists saw as higher than expected.

On the other hand, Frank Pagani, MD, associate professor of surgery at the University of Michigan Health Systems (Detroit), told the panel that 30-day mortality for the HM II was one half that of the XVE pivotal trial. He also said the implant technique “is the same as the XVE, which is the current standard of care,” but is a shorter and less difficult procedure.

The panel voted in overwhelming majorities on several conditional votes, including to require that the PAS look at the effect of sex on outcomes and to require a concurrent comparator arm (the idea of controls was dropped after some discussion).

The vote was also 11-1 on the recommendation that the label rule out use of the VAD in patients not eligible for anti-coagulation therapy, but the panel could not come to a conclusion about whether to require the use of a procedure to stanch bleeding or even whether to study the phenomenon. After imposing these requirements, the panel voted unanimously to recommend approval.

Gary Burbach, CEO of Thoratec, told Medical Device Daily that he was not surprised at the panel’s conclusion that a PAS should include a comparator population, given the discussion of requiring a controlled study. However, he said that the HMII would likely take away sales from the company’s other LVAD.

“We do expect there will be some cannibalizing” of the HeartMate XVE, he said, but “we expect the VXE will hold” a place in the market because it requires less anti-coagulation therapy. He also said that he sees “quite a bit of enthusiasm” for the HMII from doctors.

Burbach declined to speculate on market penetration, noting only that the firm will hold a conference call sometime over the next three to four months to address investor questions on this issue.

An advisory by investment banking firm BearStearns (New York) rated Thoratec’s stock as an “outperform,” noting that FDA could approve the device as early as the first quarter of 2008.

On the other hand, surgeon training could slow the pace of adoption according to the Bear Stearns advisory, which described surgeon training as “the key gating factor to device uptake speed.” The company’s shares, which trade on the Nasdaq board, gyrated between $18.78 and $20.74 yesterday, and at 3:30 p.m. U.S. Eastern time were fetching $18.95.