More than 10 hours of testimony and debate failed to convince a US Food and Drug Administration (FDA) expert advisory panel that existing evidence reasonably supports a premarket approval (PMA) application for the Neovasc Reducer device.
The Reducer is intended for people suffering from refractory angina pectoris despite guideline-directed medical therapy, who are unsuitable for revascularization by coronary bypass grafting or percutaneous coronary intervention.
The FDA’s Circulatory System Devices Panel advisory committee generally agreed in a 14-to-4 vote that the evidence provides reasonable assurance the Reducer is safe, but took a dim view on assurances of its effectiveness in a vote of 1 to 17.
On the question of a benefit/risk ratio, the vote was 3 yes, 13 no, and 2 abstentions. The panel did not vote on the approval of the PMA itself but heard several impassioned pleas from patients calling for its approval in the United States.
“People talked about the urgent need and the patients need hope, but we shouldn’t give them false hope,” Richard Page, MD, University of Vermont Medical Center, South Burlington, said. “We need to provide them something we truly believe is going to be effective and that was not proven today.”
Erik Magnus Ohman, MD, Duke University School of Medicine, Durham, North Carolina, who voted no on all three counts, said, “I voted no for efficacy because I couldn’t link ischemia, which is objective, with a device that we put in permanently when nearly half the patients had very little treatment benefit.”
The primary data set in support of the PMA was from the phase 2 COSIRA study, in which 18 of 52 patients treated with the Reducer and 8 of 52 patients treated with a sham procedure had improved by at least two Canadian Cardiovascular Society (CCS) classes, the primary efficacy outcome, at 6 months (34.6% vs 15.4%, P = .024).
In 28.8% of the Reducer group and 57.7% of the control group, no change in CCS was seen.
“This is an angina study and for 50 years the standard for angina for success or magnitude of success in minimizing or preventing angina has been a quantitative exercise test, but that’s not what we’re talking about here,” Jeffrey Borer, MD, SUNY Downstate Health Sciences University in Brooklyn, New York, said. “We’re talking about a subjective endpoint and I think that’s a real problem and just magnifies all the other problems that have been discussed.”
Several panelists questioned whether the trial truly enrolled patients with CCS class 3 or 4 angina with limited options, given that 27% of Reducer patients and 25% of controls were on none or one antianginal medication. Information was also not provided about compliance or whether patients were on therapeutic or maximally tolerated doses.
Others pointed out the potential for a placebo effect and that patients were largely satisfied with treatment despite the marked discrepancy in results. Also, the trial lacked a formal blinding assessment for investigators.
Wayne Batchelor, MD, Inova Heart & Vascular Institute, Fairfax, Virginia, took issue