FDA panel finds ‘smoking gun, but no bullet or dead bodies’ in paclitaxel devices

Members of an FDA advisory panel yesterday cited conflicting evidence from studies of paclitaxel-eluting devices in treating peripheral artery disease, with the panel’s chairman calling the data “a smoking gun, but no bullet or dead bodies at this particular point.”

A meta-analysis published in the Journal of the American Heart Assn. last December suggested that PAD patients treated with paclitaxel-coated balloons and stents could be at a higher risk for late death. Led by Dr. Konstantinos Katsanos, researchers looked at data from 28 trials to find a 68% relative risk increase in all-cause death with paclitaxel-coated devices after two years and a 93% relative risk increase after five years, compared to therapy with an uncoated device.

The study prompted the federal safety watchdog to schedule a meeting of its Circulatory System Devices Panel yesterday and today in Gaithersburg, Md., to discuss the late-death signal and whether it represents a class effect among paclitaxel-eluting devices.

In pre-meeting materials released this week, the FDA said it reviewed the data using both the JAHA analysis parameters and data from the four pivotal randomized controlled trials used to back pre-market approval bids for paclitaxel-coated devices. The agency’s analysis of the JAHA study “reproduced the same results based on fixed and random effects models shown in the paper,” raising concerns about a possible late-term death risk.

At yesterday’s hearing, medical device representatives argued that the FDA’s warnings on the potential risks is having an impact on patient care.

“[M]any clinicians, health care systems have unilaterally made the decision to withdraw these devices from their shelves,” Daniel Clair, an advisor to Medtronic (NYSE:MDT), Boston Scientific (NYSE:BSX) and Becton Dickinson (NYSE:BDX), told the panel, according to Regulatory Focus. “[F]or many physicians, the fear of potential lawsuits has led to these products being essentially unusable in the current environment.”

“The initial meta-analysis and follow up done by the FDA have flaws, which even the FDA has acknowledged in its communication,” Clair said.

But panelist Bram Zuckerman, director of the Office of Cardiovascular Devices at FDA’s Center for Devices an&d Radiological Health, said there are problems with the data submissions from medtech makers.

“Industry has stepped up to the bar and this is a dynamic process,” Zuckerman said, the website reported. “However, I would be careful about utilizing the most up to date data analyses. They have not been checked by the FDA and I can say in general terms, because of a multitude of problems, the FDA has had a lot of back and forth with each company to verify data.”

“All of our industry sponsors have indicated that in carrying these studies out longer there’s missing data and what we as a panel say is, ‘This is what makes it very difficult for us to interpret the data,'” chairman Dr. Richard Lange said, according to Medscape Medical News. “So what we’re left with is incomplete data, very good analysis, a signal, a smoking gun, but no bullet or dead bodies at this particular point.”

“We’re subjected to a forest of dueling numbers,” added panelist Dr. John Hirshfeld Jr. “The problem is that the numbers presented by industry and the numbers presented by FDA are not the same. As a consequence, we have a conundrum in terms of what weight to put on each analysis we see.”

The panel unanimously agreed on the late mortality signal in PAD patients treated with paclitaxel-coated devices, but couldn’t determine whether there’s a class effect based on the existing data, according to Medscape.