The U.S. Food and Drug Administration indicated that a premarket approval application seeking to allow the Lutonix drug-coated balloon to treat peripheral artery disease below the knee is “not approvable in its current form,” BD Chairman and CEO Vincent A. Forlenza told investors last week.
“Regarding our FDA PMA (premarket approval) submission for Lutonix below the knee: As you are all aware, we have been working with the FDA in a collaborative review process. Subsequent to the FDA advisory committee meeting on paclitaxel, the statutory review time for our (below-the-knee) PMA submission concluded, and the FDA notified us, that our PMA was not approvable in its current form,” Forlenza said during the company’s third-quarter earnings call Tuesday.
The Lutonix 035 drug-coated balloon has been commercially available since 2012. In the U.S., it is approved for use in de novo, restenotic or in-stent restenotic lesions in the native superficial femoral or popliteal arteries.
According to materials prepared by BD and presented at the FDA advisory committee meeting to which Forlenza referred, held June 19-20, there was “some numerical increase in risk” shown in the combined LEVANT 2 studies of the device but that the risk did not reach statistical significance and that there was no significant difference in mortality rate at 5 years between the device and control arms. The company’s presentation also concluded that there was “no finding of paclitaxel-related death based on an independent review of all mortality events, or any clustering of causes in death suggesting a common mechanism.”
The advisory committee meeting examined the use of paclitaxel in drug-coated balloons and stents manufactured by several companies after a meta-analysis Konstantinos Katsanos, MD, PhD, MSc, EBIR, of Patras University Hospital, Greece, and colleagues, published in December in the Journal of the American Heart Association. That manuscript reported higher all-cause mortality beyond 1 year in patients undergoing treatment of femoropopliteal disease with paclitaxel-coated devices compared to control groups in a pooled analysis of 28 randomized controlled trials.
On Wednesday, the FDA issued an updated letter to providers based on the advisory panel’s recommendations. The letter says in part that clinical studies of paclitaxel-coated devices in the peripheral arteries may continue and should collect long-term safety – including mortality – and effectiveness data. The FDA also said in this letter that patients should be informed of the late mortality signal in paclitaxel devices and that it will work with manufacturers on changing the labeling of these products to include information about the late mortality signal.
Forlenza said during BD’s earnings call that “the approval process timeline has extended out from our previous expectations, and we no longer expect approval this calendar year. We will keep you informed as we work with the FDA and make further progress.”