FDA panel recommends against approval of angina relief device
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The FDA’s Circulatory System Devices Panel recommended the agency not approve an implantable device to treat refractory angina, saying more data are needed.
The panel voted 14-4 that the device (Neovasc Reducer, Neovasc Inc.) is safe, but 1-17 that the device is not effective and 3-13 with two abstentions that its benefits do not outweigh its risks based on current data.
Neovasc is seeking approval for its treatment for patients with refractory angina despite use of guideline-directed medical therapy who are not suitable for PCI or CABG. The FDA had designated the Neovasc Reducer a breakthrough device in October 2018. The device received a CE mark in 2011, is marketed in 17 countries and has been implanted in more than 2,000 patients, according to the agency.
An executive summary by FDA staff provided to members of the panel noted that the U.S. prevalence of “no-option” refractory angina has been estimated at between 26,000 and 52,000 patients, and that 1-year mortality estimates for this population vary widely.
However, panel members said although the device likely will help its intended population, existing data did not prove that its potential benefits outweighed its potential harms.
A sham-controlled study, COSIRA-II, was planned to be conducted, but the company decided not to proceed with it, instead submitting an application based on data from a first-in-human study, the 104-patient COSIRA non-U.S. randomized trial and the REDUCER-I observational study, according to the FDA. Panel members expressed concern that the populations studied did not match the heterogeneous U.S. population, that data from secondary efficacy endpoints were often missing and that 6 months was a not long enough time for reliable safety data.
“As an interventionalist who treats a lot of these patients who are really desperate for therapy ... I think this is a safe procedure because it’s been done in over 2,000 patients and I think we would have seen something come out if it was an unsafe procedure,” panel member Wayne Batchelor, MD, director of interventional cardiology at Inova Heart & Vascular Institute in Fairfax, Virginia, the only panelist who voted yes on all three questions, said during the meeting. “I was going to vote no on effectiveness and then I switched it because the concern about the placebo effect if anything would bias toward the null and ... slightly disadvantage the device. I don’t know that it works for ischemia, but as a patient-centered outcome for simply angina, I think there’s a good chance this device does work. This is all in the context of absolutely requiring more data, linked to a requirement of a randomized controlled trial.”
Panel member Randall Starling, MD, MPH, professor of medicine at Kaufman Center for Heart Failure at Cleveland Clinic, who voted yes on safety and no on the other two questions, said he is “very sympathetic to this patient group” but was “uncomfortable with the data from the randomized trial in this sample of just over 100 patients” and found “a lack of any convincing efficacy.”
According to the summary, the device is implanted into the coronary sinus via a balloon catheter to narrow it, helping redistribute blood flow to ischemic myocardial areas. Implantation happens via percutaneous access through the right jugular vein into the coronary sinus.
“The central orifice of the device is intended to remain patent and becomes the sole path for blood flow through the [coronary sinus], leading to the development of an upstream pressure gradient resulting in the redistribution of blood from the less ischemic epicardium to the ischemic endocardium,” the FDA staff wrote in the summary.
The company asked the FDA for a panel meeting if the agency had “remaining uncertainty that the sponsor has met the statutory requirement for reasonable assurance of safety and effectiveness,” and the agency granted the request.
“The company got feedback from the FDA asking for a [U.S.] randomized trial and chose not to accept it,” panel member Jason T. Connor, PhD, founder of ConfluenceStat LLC in Orlando, Florida, said during the meeting. “They had plenty of chances to [prove] the efficacy that we all would like to have seen.” He voted yes on safety, voted no on efficacy and abstained on risk-benefit ratio.
The FDA is not required to follow the recommendations of its advisory panels, but it usually does.
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