Medical Device Daily
Despite what it considered as signals that its premarket application for use of its cryoablation system to treat atrial flutter was sailing along unhindered toward FDA approval, CryoCor (San Diego) last Thursday reported receiving a "not approvable" letter from the agency.
"We were not expecting this decision," said CEO Greg Ayers in a late-Thursday conference call.
Ayers said that the FDA's letter indicated that it had made an interpretation, different from the company's, concerning "the patient data and categorization of patients to be included and excluded in the analysis of chronic efficacy," the criteria it used in its trial supporting the application.
He said the company had already talked to the reviewer of the PMA and the chief of the electrophysiology monitoring branch of the FDA "to obtain additional information regarding comments contained in the letter" in order to determine its next steps.
Ayers said that expectations for winning approval had been based on letters from the agency – considered by the company, he said, as "routine inquiries" – suggesting that the review was proceeding without a problem.
And he indicated that the primary reason for the agency's "not approvable" decision was based on the "subjective" method required for interpreting chronic efficacy.
"The process requires complex interpretation of clinical data and can result in different interpretations as to the results," Ayers said.
"We provided analysis of our chronic data, based on what we feel were appropriate classifications of the patients and measures of effectiveness of our ablation procedure, based on clinical experience with similar patients treated with our systems outside the U.S. and with our clinical interpretation of the patients in this trial and their post-procedure clinical course."
The company, he said, was in the process of evaluating both the additional ways that it could analyze the data and "the impact of this delay" on marketing and ongoing business operations.
Throughout the call, he expressed confidence in eventually winning approval for the atrial flutter application and that the agency decision would have no impact on the company's ongoing trial for treatment of atrial fibrillation (AF) with its technology for using cold energy to treat this type of heart arrhythmia.
Questioners pressed for details concerning plans for further analysis going forward, but Ayers continually fended these off, saying it was too early in the process to lay out such details or supply an event timeline, and that he wanted to maintain "rapport" with the agency.
Enrollment in the company's AF trial was ongoing, he said, "at the rate of about 10 patients per month" and "the FDA's question about atrial flutter [does not] affect their position on the applicability of cryoablation to this much-larger patient group."
Also pressed for more details, on the financial side, was company CFO Greg Tibbitts.
He said he saw no change in guidance for the company and that as of Jan. 31, CryoCor had $29.4 million on hand. "Our objective is to make that money lasts as long as it can," with a burn rate of "about $1.3 million per month," he said.
But he too declined further to supply specifics until he had a chance to develop "models, and have the board look at them as well."
One questioner also noted the lack of a control group in the atrial flutter trial, suggesting this was a cause for agency concern.
Ayers said that the company had ruled out use of the control group approach because of next-generation developments of radio frequency ablation devices available for comparison and the inability to create a control group that was "homogeneous."
Because of this difficulty, the company had chosen to use the "predefined criteria" of chronic efficacy, which he said had been "laid out by the agency."
Use of a randomized trial with a control group, he said, "is not a part of our planning – but that's not to say we would not consider that in the future . . . the FDA did not state that they had any issues with the non-randomized nature of the trial."
The CryoCor cryoablation systems have been approved in Europe for the treatment of AF and atrial flutter, which are the two most common forms of heart arrhythmias, and several other firms are competing in this space to develop device-based treatments.