The FDA’s Circulatory System Devices Advisory Panel unanimously recommended today that the Lutonix 035 drug-coated balloon over-the-wire percutaneous transluminal angioplasty catheter be approved by the agency.
The panel voted 9-0 that the device is safe, 9-0 that it is effective and 9-0 that its benefits outweigh its risks.
“I don’t know when I’ve seen unanimity from the panel on all three questions; it’s been a long time, if ever,” the panel’s chair, Richard L. Page, MD, of University of Wisconsin School of Medicine and Public Health, Madison, Wis., said after the vote.
If approved, the Lutonix DCB (Bard/Lutonix) would be the first DCB on the market in the United States for the treatment of peripheral arterial disease. The sponsor is seeking an indication for improving luminal diameter for the treatment of obstructive de novo or nonstented restenotic lesions (≤15 cm in length) in native femoropopliteal arteries with reference vessel diameters of 4 mm to 6 mm. After discussion with the panel during the meeting today, the sponsor agreed to modify the indication to note that the intervention should be performed after pre-dilatation.
“This is a therapy for an unmet need of a population and could play a significant role in their treatment,” said panel member David J. Slotwiner, MD, of Long Island Jewish Medical Center, New Hyde Park, N.Y. “It may have a modest effect, but does not appear to present safety concerns.”
The Lutonix DCB is coated with a paclitaxel-based drug. It is compatible with a 0.035-inch guidewire, has balloon sizes ranging from 4 mm to 6 mm in diameter and from 40 mm to 100 mm in length, and is offered in working lengths of 75 cm, 100 cm and 130 cm, according to information provided by the FDA.
The sponsor is basing its case for approval on results of the LEVANT 2 US pivotal trial, a prospective, multicenter, single blind study in which 476 patients were randomly assigned to receive treatment with the Lutonix DCB or conventional percutaneous transluminal angioplasty.
The primary safety endpoint was a composite of freedom from all-cause perioperative death and freedom at 1 year from index limb amputation, index limb re-intervention or index limb-related death.
In the intention-to-treat population of the LEVANT 2 trial, the DCB was noninferior to the control in freedom from the primary safety event (83.9% in the DCB group vs. 79% in the control group; difference=4.9%; P for noninferiority=.005). In a per-protocol analysis that excluded patients if their treatment did not follow protocol-defined procedures or if inclusion criteria were violated, the difference between the two groups was not large enough to meet the noninferiority objective (DCB group, 83.7%; control group, 83%; difference, 0.7%; P for noninferiority=.08).
The primary efficacy endpoint was primary patency, defined as the absence of target lesion restenosis and freedom from target lesion revascularization. The DCB was noninferior to the control in the intention-to-treat analysis (65.2% in the DCB group vs. 52.6% in the control group; difference=12.6%; P for noninferiority=.015), but not in the per-protocol population (65.3% in the DCB group vs. 56% in the control group; difference=9.3%; P for noninferiority=.11).
A major point of discussion was that in the LEVANT 2 results, the device was less effective among US women than it was in US men or men or women from the European Union. The panel debated whether to contraindicate the device in women, but instead requested that the labeling suggest that doctors read the literature about the device’s performance among women.
“While I do have concerns about what will be in the [instructions for use], once we get a larger data set, the issues in women may turn out not to be a concern,” said panel member John C. Somberg, MD, of Rush University Medical Center, Lake Bluff, Ill. Panelists also noted that, in LEVANT 2, the US women had more comorbidities than the EU women.
The Lutonix DCB clinical trial program also included the LEVANT I European randomized study, the LEVANT 2 Safety Registry and the Global Superficial Femoral Artery Registry.
In related news, Medtronic announced that it submitted the final module of its premarket approval application for its IN.PACT Admiral drug-coated balloon.
The FDA is not required to follow the recommendations of its advisory panels, but it usually does.
For more information:
Circulatory System Devices Advisory Panel Clinical Briefing Document. PMA P130024.
Disclosure: The members of the Circulatory System Devices Advisory Panel report no relevant financial disclosures.