- Australia's Therapeutic Goods Administration on Monday issued a safety update reinforcing recommendations from FDA and the U.K.’s Medicines and Healthcare Products Regulatory Agency in the wake of a meta-analysis concluding there is an increased risk of death with using paclitaxel-coated balloons and stents to improve blood flow to the legs.
- TGA said data on adverse events in Australia haven't shown a signal like the one described by the FDA.
- Separately, device maker Philips responded to FDA’s letter to healthcare providers on the devices. The Dutch company said it remains "very confident" in the safety and performance of its Stellarex low-dose drug-coated balloon for patients with peripheral artery disease.
The meta-analysis that touched off international regulators’ renewed scrutiny of paclitaxel-coated devices to treat PAD was published in December in the Journal of the American Heart Association. It concluded there was an increased risk of death after use of the devices in the femoral and popliteal arteries and said there was an urgent need for further study.
FDA has advised physicians to diligently monitor patients with PAD already treated with a paclitaxel-coated device and consider potential increased risk of long-term mortality for patients when making new treatment recommendations.
Patients with high risk for restenosis and repeat interventions may still have a favorable risk-benefit for a paclitaxel-coated device, FDA said. The agency is working on updated labeling for paclitaxel-coated devices to include information about the late mortality signal. The agency wants more research into the long-term safety profile of the devices using new randomized trials and registry data sets, and it recommends information about the late mortality signal be added to patient informed consent documents.
Australia’s TGA said adverse events associated with the devices that have been reported to the agency relate mostly to balloon and stent deployment issues. Most events occurred on the day of implantation, and no deaths have been reported.
TGA also recommends continued diligent monitoring of patients treated with the devices, as well as a consideration of the safety signal when making treatment decisions with patients.
The Australian regulator agreed that for some patients at particularly high risk for restenosis, clinicians may determine the benefits of using a paclitaxel-coated product may outweigh the risks.
BD, Medtronic, Boston Scientific, Philips and Cook Medical have paclitaxel devices on the market.
Philips said an analysis of two randomized controlled trials showed no difference in mortality, with no device-related deaths, after three years between patients treated with its Stellarex drug-coated balloon compared to those who receive percutaneous angioplasty. The device has a coating that enables a low therapeutic drug dose of 2 micrograms of paclitaxel per square millimeter, the company said.
Philips added it is continuing to enroll patients in its Illumenate below-the-knee clinical trial and will continue to follow up on all its trials, including the Illumenate pivotal trial, European randomized controlled trial, and the Illumenate Saver registry.
BD told investors last week FDA said its premarket application for its Lutonix drug-coated balloon isn't approvable in its current form, given the clinical evidence collected to date.