UPDATED Dec. 14, 2012, at 10:30 a.m.
Last week the federal watchdog agency’s Circulatory Devices Advisory panel ruled that some cardiovascular pump makers, including Danvers, Mass.-based Abiomed, must submit already-approved medical devices for review under the more-stringent pre-market approval pathway. The various Impella devices can stay on the U.S. market in the meantime.
Although the panel acknowledged that non-roller-type cardiopulmonary bypass blood pumps are life-supporting, it recommended against shifting them to a lower-risk category for temporary ventricular support. The decision sent ABMD shares spiraling downward Dec. 7, dropping as low as $12 per share in morning trading before closing at $12.49 apiece, down 3.0%.
Jefferies & Co. analyst Raj Denhoy told MassDevice.com this morning that the FDA decision’s implications are compounded by 2 other factors: A U.S. Justice Dept. probe into Abiomed’s marketing of the Impella devices and a recent Centers for Medicare & Medicaid decision to consider a national coverage decision for them. But the root of the problem is the Protect II study, Denhoy told us, which Abiomed halted for futility reasons in December 2010.
"If you look back, the bad luck was that Protect II failed. They tried to do the right study, but because of the nuances in the design of that study it failed," Denhoy said during a telephone interview.
The Protect II trial set a low threshold for an enzyme that’s an indicator for heart attack, he explained. But because that enzyme is also released during atherectomy, and because physicians were so confident in the Impella device that they were more aggressive with atherectomies during procedures, some patients were judged to have experienced heart attacks during the trial based on their levels of that enzyme.
"If they had set that level higher, so that it couldn’t have been mimicked by this atherectomy issue, the trial probably would have been successful," Denhoy told us. "What the FDA is ultimately forcing Abiomed to do is become a real company. They tried to fly a little too close to the sun without having the data. The real gist of this is that this is work that they should have done originally, that would support all their claims and also reimbursement. They tried to push to that level without ultimately having that support, and they’ve gotten burned for it.
"What investors and Wall Street are trying to figure out is, what does all this do to growth and demand going forward?" he said.
An ironic wrinkle for Abiomed is that physicians and patients are eager to use Impella, and professional medical societies have already written its use into their guidelines. Should Abiomed be compelled to run another trial, that raises an ethical issue: How do you randomize some patients to not receive the Impella therapy?
"There’s a high level of acceptance that this thing actually works, but they’re trapped in this sort of purgatory, in that they need to produce the data," Denhoy explained. "They seem to be confident that they can, but the FDA doesn’t seem to think that there are acceptable data. Ultimately I think they’re going to have to produce some new data, perhaps in a small trial."
ABMD shares lost nearly 6% Dec. 12 after a conference call with analysts, including Denhoy, to discuss the FDA panel’s decision. Shares closed at $13.04, down 5.7% that day, after CEO Mike Minogue reported that Abiomed had its 1st formal conversation with the FDA about the panel’s decision.
"The FDA recommended that we submit a packet analysis of the totality of our data and it will be specific to Impella. It will not be on the broad category of temporary ventricular support, which is how it was described and discussed at the panel. We will submit that in advance and then we will have a face-to-face meeting with several of our physician investigators, the FDA and the company to talk about next steps," Minogue said during the call, noting that Abiomed expects to submit the data packet over the next 3 to 4 months.
Some 245 patients have been studied in clinical trials of the Impella device for use in high-risk percutaneous coronary interventions, he said, adding that about 1,000 patients are being followed in a U.S. Impella registry.
Questioned about the panel’s concern that there’s a lack of evidence supporting the safety and efficacy of Impella in high-risk PCIs compared with intra-aortic balloon pumps, Minogue stressed that the ruling applies to all makers of this type of heart pump, not just Abiomed.
"So it not only applied to us; it applied to the existing product on the market and any future products," he said. "[W]e do believe that we have, in the totality of the data, the ability to show a reasonable assurance for safety and effectiveness."
Asked about the likelihood of another study akin to Protect II, Minogue said another randomized trial is unlikely, given that there are already published society guidelines for using Impella.
"And then specifically to your comment around another study of high-risk PCI, we believe it would be unlikely that we could enroll another Protect II-like population to the control arm," he said. "I think the short answer is that the FDA has difficulty, as do physicians and companies, to randomize something when it’s already been incorporated into the guidelines. So to recommend now to randomize certain patient populations, that goes against the current guidelines, is not something that people are apt to do or have done in the past."
ABMD shares were trading at $13.02 as of about 10:30 this morning, down less than 0.1%.