UPDATE: March 22, 2019: BD Thursday pushed back against FDA's warning to avoid paclitaxel-coated balloons and stents, saying it "stands behind the robustness of its pre-clinical and clinical data" of its Lutonix drug-coated balloon.
The company said that its LEVANT 2 study data suggests that when excluding causes of mortality such as pre-existing cancer, "the broader data set confirms the safety of this product and is larger than the pooled dataset referenced in the FDA letter."
It plans to have an independent analysis completed before FDA holds its advisory committee meeting in June.
- FDA is recommending use of treatments other than paclitaxel-coated balloons and stents for most peripheral arterial disease (PAD) patients after the agency’s preliminary analysis of long-term data showed a 50% higher risk of mortality in people treated with the devices compared to a control group. FDA first flagged a possible increased risk two months ago in a letter to physicians.
- “Because of this concerning safety signal, we believe alternative treatment options should generally be used for most patients while we continue to further evaluate the increased long-term mortality signal and its impact on the overall benefit-risk profile of these devices,” FDA said Friday in an updated communication.
- The agency said it will convene an advisory committee meeting of the Circulatory System Devices Panel to discuss the long-term mortality signal and re-examine the benefit-risk profile of this group of devices.
FDA’s actions follow the publication in December of a meta-analysis in the Journal of the American Heart Association that sounded an alarm after finding a higher risk of death in patients two years after treatment with paclitaxel-coated balloons or paclitaxel-eluting stents in the femoropopliteal artery of the leg. The devices treat plaque build-up and deliver medication to help prevent the vessel from re-clogging.
In January, FDA alerted physicians to the potential mortality risk, noting the cause of the issue was undetermined, and said it was analyzing long-term follow-up results from studies that supported approval of the devices plus additional data sets. At the time, the agency said it still believed the benefits of the devices outweighed the risks. U.K. regulators have since formed their own expert advisory panel to further investigate the meta-analysis.
Within days of FDA’s initial announcement, Medtronic, maker of the IN.PACT Admiral drug-coated balloon, released five-year data from its clinical programs that showed no correlation between paclitaxel dose and long-term survival. While Medtronic issued a correction to that data earlier this month, company officials said the original conclusions remain intact. Medtronic is one of several companies that sell drug-coated balloons and stents. Others include Cook Medical, Becton Dickinson through its acquisition of C.R. Bard, and Boston Scientific.
In Friday’s communication, FDA said three trials with five-year follow-up data on 975 patients combined showed an approximately 50% increased risk of mortality in subjects who were treated with paclitaxel-coated products, compared to those treated with uncoated devices.
FDA said it intends to conduct additional analyses to determine whether benefits continue to outweigh the risks for approved paclitaxel-coated products. It advised caution in interpreting the latest data, noting there is a limited amount of long-term information, the studies were not intended to be pooled, and the specific cause of the increased mortality is unknown.
But because of the concerning safety signal, FDA said, alternative treatments should be used for most patients while the agency continues to evaluate the issue. For patients at particularly high risk for restenosis, or re-clogging of the artery, physicians may determine that the benefits of a paclitaxel-coated device outweigh the risks, FDA said.
The agency said it plans to hold an advisory panel meeting to discuss the magnitude of the long-term mortality signal, including plausible reasons, re-examine the benefit-risk profile of the devices, consider modifications to clinical trials, and guide other regulatory actions as needed. The date and location of the meeting will be announced in the coming weeks, FDA said.