Advisory Panel Gives Unanimous Recommendation for FDA to Approve Bard's Lutonix Drug-Coated Balloon

June 12, 2014—Bard Peripheral Vascular announced that a Circulatory System Devices Panel of the Medical Devices Advisory Committee of the US Food and Drug Administration (FDA) provided a unanimous favorable recommendation to the FDA for approval of the Lutonix drug-coated balloon (DCB) percutaneous transluminal angioplasty (PTA) catheter for the treatment of peripheral arterial disease (PAD) in the United States.

The FDA panel held an all-day public meeting in Germantown, Maryland, to discuss, make recommendations on, and vote on information related to the premarket approval (PMA) application for Lutonix DCB that was submitted by Bard in November 2013.

The FDA will next consider the positive recommendation of the advisory panel. The Lutonix DCB is currently available commercially in Europe.

Bard stated that the Lutonix DCB is currently under review by the FDA for improving luminal diameter and reducing the incidence of restenosis 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. If approved, it is expected that the Lutonix DCB will be the first FDA-approved DCB available in the United States, noted the company.

The Lutonix DCB is an over-the-wire PTA catheter with a paclitaxel-based drug coating on the surface of the balloon. The device is compatible with an 0.035-inch guidewire and has balloon sizes ranging from 4 to 6 mm in diameter and 40 to 100 mm in length. The Lutonix DCB catheter has working lengths of 75, 100, and 130 cm.

Kenneth Rosenfield, MD, who is Section Head for Vascular Medicine and Intervention, Massachusetts General Hospital in Boston, served as LEVANT 2 coprimary investigator.

In the company’s press release, Dr. Rosenfield commented, “The PAD patient population is growing and the variety of treatment needs for these challenging patients is increasing. There is a need to improve upon the current well-established treatment modality and the Lutonix DCB can be another tool to treat PAD in the difficult anatomy of the femoropopliteal artery without leaving an implant behind.”

As summarized by Bard, the data presented at the advisory committee meeting included 1-year primary endpoint data from the LEVANT 2 pivotal study, which is a global, prospective, single-blind, randomized, 54-site study (42 sites in the United States and 12 in Europe) that enrolled all patients under one protocol. 

According to the presentation by John DeFord, PhD, Senior Vice President, Science, Techologies and Clinical Affairs of C.R. Bard, Inc., at 1 year, LEVANT 2 demonstrated superior primary patency of the target lesion with the Lutonix DCB for the efficacy endpoint (65.2% vs 52.6%; P < .0015 on an intention-to-treat analysis) and noninferiority for the safety endpoint; both endpoints were compared to standard PTA.

The company also reported secondary efficacy endpoint results at 1 year for patients randomized to treatment with the Lutonix DCB. These results demonstrated superiority in binary restenosis (26.5% vs 43.2%; P < .001 by Kaplan-Meier time-to-event analysis at 365 days) when compared to uncoated balloons, and measureable but not statistically significant improvement in freedom from target lesion revascularization (TLR) (89.7% vs 84.8%; P = .1673 by Kaplan-Meier time-to-event analysis).

According to the company, two key aspects of the study design differentiate this trial from recent SFA studies. First, unlike some other SFA trials, the LEVANT 2 clinical trial did not count bailout stenting as a primary patency or TLR failure. Second, to reduce the potential introduction of bias into the subjective clinical decision for revascularization, the protocol required the clinical assessment to be performed by a physician who was blinded to the treatment group and the Doppler patency measurement.

Bard explained that this methodology of blinding the evaluating physicians in SFA trials is unique to LEVANT 2. Published data suggest that trials with less rigorous blinding methodologies have shown physicians to intervene more often in the control arm than in the treatment arm, even when presented with similar objective results such as binary restenosis. This can have a significant impact on subjective results, such as TLR. For example, the blinding methodology in LEVANT 2 showed very similar rates of intervention when binary restenosis occurred in either arm of the trial.