Months after FDA publicly scrutinized a late mortality signal among patients with peripheral artery disease in the femoropopliteal artery who received paclitaxel-administering devices, manufacturers of the implicated stents and balloons are rolling out updated labels acknowledging the issue.
Simultaneously, companies are defending their products in newly released safety analyses, although FDA has questioned if currently available data is robust enough to settle concerns about the signal. The American Heart Association journal Circulation on Tuesday published an examination of three-year patient-level data on Philips' Stellarex DCB which the company said showed "no difference" in patient mortality compared to standard-of-care percutaneous angioplasty.
That fresh look at clinical trial data followed a similar showing by BD over the weekend at the Cardiovascular Research Foundation's Transcatheter Cardiovascular Therapeutics (TCT) symposium, where researchers presented a data analysis based on three controlled trials of the company's Lutonix DCB. That analysis, published in the Journal of the American College of Cardiology: Cardiovascular Interventions, found no significant differences in mortality rates.
The five companies that engaged with FDA on its two-day advisory committee meeting — BD, Philips, Medtronic, Cook Medical and Boston Scientific — had label changes approved by the agency Sept. 13 via PMA supplements.
FDA announced Aug. 7 it was "taking additional steps to address this signal, including working with manufacturers on updates to device labeling" after gaining insight from its Circulatory System Devices Panel and an agency-run meta-analysis. Both followed an FDA alert in January acknowledging findings from a JAHA meta-analysis indicating "strong evidence" that risk of death is "significantly increased" in patients beyond one year after receiving the devices.
Philips, Medtronic and Cook Medical all confirmed to MedTech Dive they have recently updated their instructions for use with a warning and additional clinical data summary information, with some also mentioning updates to patient brochures.
"There is uncertainty regarding the magnitude and mechanism for the increased late mortality risk, including the impact of repeat paclitaxel-coated device exposure," the added warning reads. "Physicians should discuss this late mortality signal and the benefits and risks of available treatment options with their patients."
A Boston Scientific representative said the label change is "being implemented per FDA guidance over the next several weeks." The global clinical trial of its Eluvia stent will follow patients to five years, as will its randomized trial comparing Eluvia to bare metal stents. The latter trial is currently enrolling, the spokesperson said.
A BD spokesperson said the company was "not able to confirm definitive timing when the label change will take effect."
At TCT, discussions of the paclitaxel safety signal were "more mature" than some of the earlier ones, symposium co-director Ajay Kirtane, director of the cardiac catheterization labs at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, told MedTech Dive.
According to event coverage from analysts at Cowen, FDA's cardiovascular devices office head Bram Zuckerman praised the authors of the original JAHA meta-analysis, and highlighted FDA's August safety notice, label revisions and efforts to ensure long-term clinical studies are run to completion. He also expressed agency support for manufacturers' additional analyses of the long-term data sets, according to a Cowen note.
A Medtronic spokesperson also highlighted an updated version of a Medicare beneficiary data analysis by Eric Secemsky, director of vascular intervention at Beth Israel Deaconess Medical Center's Cardiovascular Institute. That analysis found no difference in survival among more than 150,000 patients followed for two to four years.
"The CMS data is an example of a large data set that may provide us more insight as they have the power to investigate the signals found in the RCTs further," the spokesperson said in an email to MedTech Dive.
Medtronic will present global four-year data on its IN.PACT Admiral balloon at VIVA (Vascular Interventional Advances) in November.