Medical Device Daily Associate

For only the second time since its creation in 2000 by Les Weinstein, ombudsman for Center for Devices and Radiological Health (CDRH), the FDA’s Medical Devices Dispute Resolution Panel (MDDRP) is set to convene a hearing to determine the fate of a company’s technology.

The five-person panel is scheduled to meet Dec. 15 to review Acorn Cardiovascular’s (St. Paul, Minnesota) premarket approval application (PMA) for its CorCap cardiac support device (CSD), a mesh wrap implanted around the heart to provide ventricular support and to reduce ventricular wall stress in patients with dilated cardiomyopathy and symptomatic heart failure and worsening despite optimal medical management.

The panel serves as final recourse for companies in their bid to win device approval when all other avenues have failed them or if they decide that they don’t want to do any further trials, as was the case with Acorn. An FDA panel recommended against the PMA for CorCap by a 9-4 vote in July 2005 (Medical Device Daily, June 23, 2005).

The panel’s main concerns centered on what it felt were gaps in New York Heart Association (NYHA) functional class follow-up data and the lack of substantial evidence of efficacy, compared to the control group in the trial.

Panel members also expressed concern about potential problems with how the CorCap device might impact the effectiveness of other surgical procedures, if necessary, after the device implantation. That concern pinpointed trial data indicating an 11% chance of major heart surgery two years after CorCap implantation, despite being significantly below the 26% rate of heart surgery for the control group.

Rich Lunsford, Acorn’s president/CEO said that the company was very proactive after the turndown, and he told MDD that they were meeting with the agency less than a month later to determine how to gain approval.

In a “non approvable” letter from the FDA, Lunsford said that the company was given several options to address the panel’s concerns.

“One of those options was to conduct a subsequent analysis that would identify where the patients did the best within our subset, which is what we chose,” he said.

The company presented that data to the FDA this past January and received a second “non approvable” letter in February “not saying why [the device] was non-approvable, it just said we want you to go out and get additional patients.” In essence, they wanted the company to do another trial.

Lunsford expressed surprise that the issue had reached this point, explaining that the company had worked closely with the agency prior to submitting its data to the FDA panel in June 2005.

“This is the largest cardiac surgery multi-center trial that’s ever been conducted,” he said, with more than 300 patients enrolled at 29 sites in the U.S. and Canada.

In the trial, the CSD group showed improvements in several categories. This group had more patients improved according to NYHA class (38% vs. 27%) and fewer patients “worsened” (37% vs. 45%). The CSD group had fewer follow-on major cardiac procedures (such as heart transplant, implantation of a ventricular assist device or need for electrical stimulation therapy), compared to the control group. And using a quality-of-life assessment, the CSD group reported greater improvement in quality of life over the control group.

“Acorn designed the CorCap trial with input from CDRH, including the primary endpoint, secondary endpoints, and success criteria,” said Steve Anderson, vice president of corporate assurance for Acorn, in a statement. “Since the trial met all its success parameters and numerous independent clinical and statistical experts have affirmed the robustness of the trial, we believe that the MDDRP will agree that the CorCap meets the FDA approval requirements of reasonable assurance of safety and effectiveness.”

Acorn disagreed with this the FDA’s assessment that an additional trial was needed and filed a request for referral to the MDDRP, that requrest granted by Weinstein in June.

Lunsford noted that the company’s trial for the device has cost it nearly $30 million since it began in 2000, and he wonders what more the agency needs to grant approval, particularly since he said they wanted the company to use “similar endpoints” for the new trial.

If the MDDRP needs to take a vote, Lunsford said, its recommendation will then be forwarded to the head of the CDRH, Dan Schultz, for final action. While Lunsford noted that Schultz could turn down a positive MDDRP recommendation, he does not see this as a likely scenario.

“If his panel votes to approve the PMA, we’re looking at this as highly likely that we’ll get an approval.”

The CorCap fills a gap in the treatment continuum of heart failure, Lunsford said, and could be most useful for NYHA Class III patients, moderate cases of heart failure patients that are not doing well on medical therapy, a pool that he said ranged from 1 million to 1.5 million of the 5 million U.S. heart failure patients.

He said the company feels that it really has nothing to lose by pursuing the dispute resolution pathway.

“Everything in the company is based on the success of this approval, so we felt that the decision was pretty easy,” especially since the other option of doing another trial could have taken the company another three years and $15 million to $20 million.

“We are looking forward to the opportunity to present this data to the dispute panel as we are confident in our clinical study and outcomes. Additionally, heart failure clinicians have supported the CorCap CSD as safe and effective and an important option for appropriate patients who are suffering from heart failure and do not have other therapeutic options.”

While the company is exploring poorly charted waters, it is not the first to attempt its navigation. That honor goes to Lifecore Biomedical (Chaska, Minnesota). Its Intergel Solution for the reduction of adhesions following gynecological surgery was approved by the panel in a 4-0 vote in September 2001 (MDD, Sept. 7, 2001). That product was subsequently voluntarily withdrawn by the company in March of 2003 after complaints about it, primarily related to off-label use.

Another device company also is headed toward the dispute resolution pathway. Cardima (Fremont, California) in July said it would go before the panel to pursue a PMA for its Revelation Tx Micro-catheter system for the treatment of atrial fibrillation, turned down by the agency in 2003 (MDD, June 2, 2003). It is scheduled for a panel meeting about a month after Acorn’s presentation.

Cardima’s device is a linear ablation microcatheter system using radio frequency to create linear lesions in arrhythmia-causing tissue to restore normal sinus rhythm to the heart.

No Comments