BD issues statement on FDA relating to paclitaxel-coated devices and long term mortality

BD (Becton, Dickinson and Company) issued the following statement related to the recent letter from FDA to health care providers regarding paclitaxel-coated devices: In its March 15 letter, the FDA stated, based upon their preliminary analysis of long-term follow-up data, that they see a potentially concerning signal of increased long-term mortality regarding the paclitaxel-coated device use. The FDA acknowledged that the cause for the increased risk of mortality is unknown, that there is a limited amount of long-term data (which creates variability in estimating mortality risk) and that the data was not designed to be pooled. Yet, the FDA determined to issue the letter primarily, it would appear, on a limited review of data from less than 1,000 patients combined from three studies with five-year data (completed by BD, Medtronic and Cook Medical).

BD's LEVANT 2 study enrolled 1,189 patients for the FDA panel's safety evaluation; this intent-to-treat (ITT) population was reevaluated at five years and we do not see a signal of increased long-term mortality in this large patient cohort (p=.198). While subset analysis of the randomized portion (476 patients) of the LEVANT 2 study did cross the line to significance (p=.046) at five years, the broader data set confirms the safety of this product and is larger than the pooled dataset referenced in the FDA letter.

BD has reviewed the patient level data from randomized portion of the LEVANT 2 study extensively. There are several known confounding factors for mortality over the five-year period. Said simply, there are causes of mortality for some participants that could not reasonably be attributed to paclitaxel (e.g., pre-existing cancer). When excluding those individual deaths, the subset analysis of the randomized portion no longer crosses the line to significance at five years. We have also engaged an independent third-party contract research organization (CRO) to repeat our analyses and perform its own. In addition, we are collaborating with other industry stakeholders, the FDA and the VIVA Physicians Group to support an independent patient-level meta-analysis. We plan to complete these independent analyses prior to the FDA's Advisory Committee Meeting (panel) that is anticipated for mid-June 2019.