FDA Advisory Panel Gives Nod to Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease

In a unanimous vote, the Circulatory System Devices panel of the US Food and Drug Administration (FDA) recommended approval of a paclitaxel-coated balloon for the treatment of femoropopliteal artery disease. The panel voted 9-0 on June 12, 2014, with the opinion that available data demonstrate a reasonable assurance of safety and efficacy.

If approved, the Lutonix DCB (CR Bard; Murray Hill, NJ) would become the first drug-eluting balloon (DEB) to reach the US market. The indication sought is for improvement of 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 to 6 mm.

“This is a patient group and a disease location that is notoriously hard for us to treat,” advisory panel member E. Magnus Ohman, MD, of Duke University School of Medicine (Durham, NC), told TCTMD in a telephone interview. “The panel recognized the need for developing better treatment strategies than what is currently available in this country. The uniform vote reflects that.”

Surprising Finding in Women

Much of strength behind the FDA panel’s recommendation comes from the multicenter, randomized controlled LEVANT-2 trial, which compared the DEB with standard balloon angioplasty for the treatment of femoropopliteal artery lesions in 476 patients across 55 global sites. In the intention-to-treat analysis, the primary patency rate was higher in the DEB arm than in the standard balloon arm (65.2% vs 52.6%; P = .02). However, a statistically significant difference in primary patency was not detected in the per-protocol population (P = .11).

The primary safety endpoint—a composite of freedom from perioperative death and limb amputation, re-intervention, or limb-related death at 1 year—was similar between the DEB and standard balloon groups (83.9% vs 79.0%; P = .005), meeting the noninferiority objective in the intention-to-treat analysis but again, not in the per-protocol analysis. Overall freedom from primary safety event was 83.7% for the DEB and 83.0% for the standard balloon group (P = .080).

Dr. Ohman said while there was discussion among the panel regarding the lack of effect in the per-protocol population, the overall assessment was that the intention-to-treat analysis “was clear cut.” He added that the panel felt that the per-protocol analysis may have been confounded by the use of multiple types of balloons in the control arm.

In a surprising development, Dr. Ohman said the subgroup analysis suggested a lack of response among women. The panel spent substantial time trying to pinpoint whether there was a true differential response in women vs men, he said, but the issue was complicated by a number of confounders including smoking status.

“We walked away thinking this may be a true finding, but we certainly need more information,” Dr. Ohman observed. “It could be related to sample size, but we just don’t know,” he said, adding that the panel made a number of recommendations for ongoing study of women as well as smoking status.

Another issue was that documents provided to the panel by the sponsor included a suggestion of diminished treatment effect in the DEB group at 24 months.

“That was discussed, but the number of patients [followed] to 24 months was much less than 12 months so there was uncertainty regarding longer-term treatment effect. It is of interest but that’s not where most of the data was,… and therefore the panel suggested future studies up to 2 years,” Dr. Ohman said.

Paving the Way

The FDA’s positive reaction to the DEB potentially paves the way for more such devices. Earlier this week, Medtronic (Minneapolis, MN) announced that it had submitted the final module of its premarket approval application for the IN.PACT Admiral DEB.

Much of the application centers on data from the IN.PACT SFA trial, which demonstrated lower 12-month rates of clinically driven TLR with the DEB compared with standard balloon angioplasty (2.4% vs 20.6%; P < .001) as well as better primary patency (82.2% vs 52.4%; P < .001).

Also included in Medtronic’s application are outcomes from the first 650 patients in the IN.PACT Global study, which is expected to provide data about complex anatomical and clinical characteristics in this hard-to-treat patient population.

Source:
US Food and Drug Administration. LUTONIX 035 Drug Coated Balloon (DCB) PTA Catheter [executive summary]. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices
/MedicalDevicesAdvisory Committee/CirculatorySystemDevicesPanel/UCM400614.pdf. Published June 10, 2014. Accessed June 12, 2014.

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