Endologix Responds to FDA Safety Communication on Risk of Type III Endoleaks in AFX EVAR Grafts

October 28, 2019—The FDA announced that it is evaluating new information on the risk of type III endoleak with the AFX endovascular grafts (AFX with Strata, AFX with Duraply, AFX2 [Endologix]) for the treatment of abdominal aortic aneurysms (AAAs).

The new data were presented at the American College of Surgeons Clinical Congress 2019, held October 27–31 in San Francisco, California. Kara A. Rothenberg, MD, et al published the study abstract online in the conference supplement of Journal of the American College of Surgeons (2019;229:S334).

In the FDA safety communication (in full here), the agency advised that health care providers and patients should be aware that new data from an integrated health care system suggest there may be a higher than expected risk of type III endoleaks occurring with the use of AFX with Duraply and AFX2 endovascular grafts. In June 2018, the FDA communicated about the greater risk of type III endoleaks occurring with the AFX with Strata device compared with other endovascular graft systems, which can result in serious injury.

According to the FDA, Rothenberg et al found that there was a 2.5% cumulative probability of additional procedures needed to treat type III endoleaks at 2 years of follow-up for patients with AFX endovascular grafts (95% confidence interval, 1.5–4.2). Granting the study’s limitations, the FDA noted that the abstract provides published results from the largest United States cohort of patients receiving AFX endovascular grafts.

The FDA noted that it recognizes the following limitations of the data presented in the abstract:

• A small number of patients with AFX2 (n = 32 patients with AFX2; n = 197 patients with AFX with Duraply; n = 374 patients with AFX with Strata)
• The results were not stratified by type IIIa and type IIIb endoleak
• No comparison of the results to other endovascular graft systems

The agency will continue evaluating the new data.

The FDA stated that lifelong follow-up is recommended for patients treated with any endovascular graft. Additionally, it is emphasizing the importance of at least yearly lifelong follow-up for all patients who have any type of AFX endovascular graft to monitor for type III endoleaks.

The FDA has reviewed data provided by Endologix from the company's ongoing LEOPARD clinical trial of patients with AAAs who randomly received either an AFX endovascular graft device with Duraply (AFX with Duraply or AFX2) or an FDA-approved endovascular graft from other manufacturers. In contrast to the registry data, the most recent results indicate that the cumulative probability of type III endoleaks is 1% for AFX devices and 0% for other endovascular grafts. The follow-up is limited (ie, data are not available on all patients out to 3 years), and results from this trial may represent type III endoleak rates under ideal circumstances, such as closer adherence to the labeling with regard to patient selection and treatment instructions.

The FDA concluded that it will continue to evaluate information from several sources—including the manufacturer and real-world data—about the risk of type III endoleaks for AFX endovascular grafts with Duraply graft material (AFX with Duraply and AFX2) as compared with AFX endovascular grafts with Strata graft material and with other endovascular graft systems.

On October 29, Endologix responded to the FDA update regarding type III endoleaks with the AFX endovascular AAA system.

In the company’s announcement (in full here), Matt Thompson, MD, Chief Medical Officer of Endologix, stated in part, “In our view, the small number of patients with AFX2 at 2 years (13 patients) prevents any clinically meaningful interpretation of these findings. The FDA update provides certain recommendations for patients implanted with AFX, including the need to undergo lifelong yearly surveillance, a practice that is already detailed in the AFX system’s instructions for use as well as in Endologix’s 2016 AFX safety notice and is standard practice with all aortic endografts.”

Endologix’s Chief Executive Officer, John Onopchenko, noted that the company’s current commercially available versions of the AFX system (the AFX Duraply and AFX2 products) are manufactured using a different expanded polytetrafluoroethylene (ePTFE) processing methodology than AFX Strata and include additional product improvements. He stated that the data support the company’s conclusion that changes to the ePTFE manufacturing process from Strata to Duraply, along with updates to the AFX indications for use, are associated with a reduction in the occurrence of type III endoleaks for the AFX system.

Mr. Onopchenko concluded, “We remain confident that the AFX2 device is a safe and effective product when used as indicated, and we will work diligently to understand the outcomes presented by Rothenberg et al as part of our continuing commitment to ensure that the interests of all endovascular aneurysm repair patients, including those implanted with the AFX system, are being prioritized and addressed.”

Data pertaining to the company’s current analysis of the AFX system may be found in the Endologix annual clinical updates, which the FDA reviewed and subsequently referenced in its update.