FDA Panel Weighs Risks and Benefits of Endologix AFX Devices, Then Reviews Long-Term EVAR Performance and Surveillance

November 4, 2021—The Circulatory System Devices Panel of the Medical Device Advisory Committee of the FDA Center for Devices & Radiological Health held a 2-day meeting to address the use of endovascular aortic repair (EVAR) devices for the treatment of abdominal aortic aneurysms (AAAs). The FDA released 24-hour summaries of the panel discussions.

On November 2, the panel met to discuss and make recommendations on the benefit-risk profile of the AFX endovascular graft system (Endologix LLC) with regard to the risk of type III endoleaks, as well as to provide input on the totality of data on AFX devices and whether further actions are necessary.

On November 3, the panel was convened to discuss and make recommendations on the continued safety and effectiveness of endovascular stent grafts for AAA treatment and ways to improve real-world data collection on long-term device performance for currently marketed devices and future technologies.

During the session focusing on the Endologix AFX platform of devices, the panel considered questions on (1) the totality of the data available on the device, (2) the device’s benefit-risk profile, and (3) additional clinical data.

The FDA summary reported the following panel consensus:

On the strength of the evidence for the AFX family of devices (and the AFX2 device in particular):

• “The data show a clinically meaningful increased risk of type III endoleaks associated with the AFX with Strata device. For the AFX2 device, data were insufficient to show that the type III endoleak risk has been adequately addressed.”

On the effectiveness of Endologix efforts to lower the type III endoleak risk:

• “The sponsor’s mitigation strategies, including labeling updates, did not adequately lower the type III endoleak risk and failed to identify patients at increased risk.”

On additional strategies that could prevent, mitigate, or treat type III endoleaks associated with the AFX devices:

• “Patients should be informed of the type III endoleak risk and the importance of annual follow-up. A shared decision-making process should be included in treatment decisions regarding the AFX2 device.”

On whether the totality of the data continue to support that the device benefits outweigh the risks:

• “A majority of panelists did not agree that the benefits outweighed the risk for routine use of AFX2 for treatment of [AAAs]. However, the majority of panelists supported continued availability of the device in selected patient populations and in situations in which alternative treatments are not available. In all patients treated with AFX devices, long-term surveillance is warranted.”

On the need for additional clinical data to further evaluate the device safety and effectiveness:

• “Additional clinical data are needed to further evaluate the safety and effectiveness of the AFX family of devices, particularly the currently marketed AFX2 device.”
• “The panel recommended expanding analyses from currently available data sources such as the Vascular Quality Initiative registry and other analyses using Medicare claims data. They acknowledged the limitations with regard to the delays in data availability, lack of device model identification, and lack of specific data on type III endoleaks.”
• “The panel emphasized the importance of timely data collection and analysis to evaluate type III endoleak risks associated with the AFX2 device. The panel recommended patient follow-up to 5 years with some panelists favoring to data beyond 5 years.”
• “Several panelists recommended collecting clinical outcomes in the selected indications, such as patients with small access vessels and occlusive peripheral vascular disease patients; these data would define the safety and effectiveness of the AFX2 in these selected conditions.”
• “The panel also emphasized the importance of collecting patient-centric and quality of life data. Finally, they emphasized the importance of collecting annual CT imaging data on all AFX patients.”

On the second day of the meeting that considered endovascular stent grafts in general to treat AAA, the FDA questions addressed (1) near-term and long-term safety and effectiveness of EVAR stent grafts, (2) which real-world clinical events should be assessed in long-term outcomes and the importance and feasibility of capturing images in long-term event surveillance, and (3) whether strengthening existing real-world surveillance is needed to evaluate long-term EVAR performance.

In the summary of the November 3 session, the FDA reported the following panel consensus:

On the safety and effectiveness of endovascular stent grafts in the treatment of AAAs stratified by near-term and long-term outcomes:

• “The short-term benefits of EVAR versus open surgery are well-established. However, although newer-generation EVAR devices perform better than first-generation devices, EVAR benefits versus open surgery may not be maintained in the longer term, due to higher rates of aortic reintervention and other device and aortic complications in EVAR patients.”

On which real-world clinical outcomes should be assessed in a long-term EVAR surveillance system:

• “A real-world surveillance system should assess endpoints of all-cause mortality, aneurysm-related mortality, aortic rupture, and aortic reintervention. The reintervention endpoint should capture the reason for reintervention and type of reintervention performed.”

On the importance and feasibility of capturing imaging outcomes in real-world surveillance:

• “Real-world imaging surveillance should assess endoleaks, aneurysm size, and device patency because these endpoints are clinically important and can be reliably captured. Loss of device integrity and device migration are less feasible to evaluate at all sites but could be assessed at a subset of centers using standardized imaging protocols with core lab review. Along with the need for long-term imaging data, a change in culture among patients, health systems, and physicians is required to increase patient compliance with follow-up imaging recommendations post-EVAR.”

On real-world surveillance:

• “Strengthening real-world surveillance is needed to evaluate long-term EVAR performance.”
• “A real-world surveillance infrastructure should capture data on a diverse patient population and should not be limited to academic medical centers. Serial enrollment reduces selection bias, and data monitoring and auditing plans are required. At present, there is no single real-world surveillance infrastructure that can meet the needs of all stakeholders; collaboration among data collection platforms will be needed.”
• “The surveillance system should collect information on the specific device model(s) used and baseline patient clinical and anatomic characteristics. These data are needed to identify early safety signals. Ease of use by physicians and incorporation of data from multiple data collection systems are important considerations.”

On frequency and duration of real-world surveillance:

• “Patients should complete follow-up visits 30-days postimplantation and annually thereafter. As is outlined in the current professional society guidelines, concerning findings from 30-day imaging should prompt a 6-month follow-up visit. The proposed surveillance infrastructure should collect data through 10 years post-EVAR.”

On strategies to incentivize relevant stakeholders to participate in real-world data collection on a routine basis:

• “Support is needed for data entry, which is a burdensome rate-limiting step. Voluntary participation would not likely lead to a successful real-world data collection system. A surveillance system that provides value to participating health systems would be needed. A tiered approach could be considered so that health systems can choose to participate to a greater or lesser degree.”

On stakeholder collaboration to maximize long-term follow-up compliance and data quality on EVAR device performance:

• “The FDA should act as the convening party and encourage data sharing and active participation among stakeholders. Patients and patient advocacy groups should be involved in this collaboration, and patient input should be considered in the design of real-world data collection platforms.”