An FDA advisory panel on paclitaxel-eluting devices for treating peripheral artery disease yesterday found that the mortality signal indicated by a meta-analysis last year exists but that further study is needed to determine whether it’s a class effect and to pin down the cause of death.
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 two-day meeting of its Circulatory System Devices Panel in Gaithersburg, Md., to discuss the matter. The first day ended with the panel citing conflicting evidence, with the panel’s chairman calling the data “a smoking gun, but no bullet or dead bodies.”
Although the panel was unanimous in agreeing that the devices benefit patients, discussion during the hearing’s second day covered how to convey the risk-benefit consideration to patients, weighing short-term benefit and improved quality of life against the late mortality risk given the inconclusive data, according to media reports.
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.
Yesterday the panel concluded that more data is needed to establish whether the signal indicates a class effect. Results from large Medicare and real-world data sets gave a contradictory signal, showing equivalent mortality rates for paclitaxel-eluting and drug-free devices.
Industry weighs in
The FDA-approved paclitaxel-eluting devices in question include two drug-eluting stents – Cook Medical‘s Zilver PTX the Eluvia DES made by Boston Scientific (NYSE:BSX) – and three drug-coated balloon: Lutonix, made by Becton Dickinson (NYSE:BDX); the In.Pact Admiral made by Medtronic (NYSE:MDT) and the Stellarex device made by Royal Philips (NYSE:PHG).
Medtronic, BD and Boston Scientific each issued responses to the FDA panel hearing, standing by the safety and efficacy of their respective devices.
“For Medtronic, patient safety is our top priority – and has been since our company’s founding more than 60 years ago. These panel deliberations are critically important as the Food & Drug Administration, societies, physicians, and industry consider and address the recent questions around the safety of paclitaxel devices in peripheral arterial disease above-the-knee. As an industry leader, we take our responsibility to patients and physicians very seriously and look forward to further collaboration on a response to the panel’s recommended next steps,” the world’s largest pure-play medtech firm said. “Medtronic remains steadfast in our leadership and commitment to data transparency and continues to encourage collaboration across industry and regulatory stakeholders around the world to further address this issue.”
“Over the past several months, BD has been working diligently to obtain all available patient follow-up data and collaborating with FDA, professional clinical organizations and industry to investigate the important issue of DCB safety. BD continues to stand behind the safety of its Lutonix DCBs and is committed to improving the quality of life for patients with PAD. BD will continue to collaborate with FDA, industry and professional organizations to collect and analyze data for the benefit of patients. To ensure patients with PAD continue to receive the best care possible, BD will continue to ensure physicians and patients have access to BD’s broad range of treatment options for this serious disease,” the Franklin Lakes, N.J.-based company said.
“Boston Scientific shares the agency’s dedication to providing the best care possible for the 8.5 million patients in the U.S. suffering from peripheral artery disease. Peripheral devices with paclitaxel, including the Boston Scientific Eluvia drug-eluting vascular stent system, are a critically important therapeutic option which have provided relief to hundreds of thousands of patients worldwide who are suffering from PAD,” the Marlborough, Mass.-based company said, according to Vascular Disease Management. “When considering the panel recommendations, it is important to understand that data on the Eluvia stent was not included in the meta-analyses demonstrating a late mortality signal. Additionally, the Eluvia stent is unique in its design, dose and drug delivery, as it is the only paclitaxel-based device which uses a polymer to enable a controlled, sustained drug release. The Eluvia stent has the lowest drug dose density of any paclitaxel-based peripheral device, up to 20 times lower than other drug-coated devices.”
QT Vascular, which is running an investigational device exemption trial for its Chocolate Touch drug-coated balloon, touted it as the sole DCB with a drug-delivery mechanism designed to protect the artery from torsional stress and minimize dissection.
“The company plans to continue with the enrollment of patients in its U.S. IDE clinical trial,” QT Vascular said. “All DCBs that were discussed at the Panel are based on Plain Old Balloon Angioplasty (POBA) catheters.”
Updated June 25, 2019, with comment from QT Vascular.