Endovascular treatment of patients with infrarenal abdominal aortic aneurysms with relevant characteristics.

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Committee: Circulatory Devices Panel of the Medical Devices Advisory Committee

Indication: Endovascular treatment of patients with infrarenal abdominal aortic aneurysms with relevant characteristics.

Drug/Device: AAA Stent Graft System

Sponsor: INCRAFT®

Links:

 

Relevant Question 1: Based on data in the briefing materials and presentations at today’s meeting, do you believe that there is reasonable assurance that the INCRAFT® AAA Stent Graft System is safe for use in patients who meet the criteria specified in the proposed indication, while considering the additional procedures needed to maintain effectiveness?

Vote Result: Yes: 11 No: 4 Abstain: 0

 

Relevant Question 2: Based on data in the briefing materials and presentations at today’s meeting, do you believe that there is reasonable assurance that the INCRAFT® AAA Stent Graft System is effective for use in patients who meet the criteria specified in the proposed indication?

Vote Result: Yes: 14 No: 0 Abstain: 1

Unique challenges

The INCRAFT® AAA Stent Graft System treats abdominal aortic aneurysms (AAAs), a phenomenon where a weakened aorta wall leads to dangerously enlarged blood vessels. Over time, this can lead to a life-threatening hemorrhage. Approximately 1.5 million Americans suffer from this phenomenon, with 200,000 diagnosed every year.

What makes the INCRAFT® AAA Stent Graft System different from similar marketing products is that it is oriented to specific patients with small femoral or iliac arteries or heavily calcified or tortuous vessels. Compared to the similar device in market, the serious complications that afflict these patients could be relieved by this device.

Studies began in the United States and Japan in July 2012, concluding in August 2013.

First pivotal study was granted with full approval on June 27, 2012. The pivotal study was designed to evaluate the safety and effectiveness of the INCRAFT device. Premarket application was filed in February 2015. INCRAFT received Not Approvable letters in July 2015, April 2016 and July 2017. The letters requested further information on:

  1. Root cause analysis and mitigation strategy of transrenal stent fracture;
  2. Intraprocedural Type I and Type IV endoleaks, and the potential for aneurysm enlargement over time for these endoleaks;
  3. Device occlusion and other patency-related events;
  4. Proximal limb migration; and
  5. Deployment of the implant at unintended locations.

Corresponding to the requests, Cordis submitted a response to the July 6, 2017 official Not Approvable letter, with available clinical data out to 5 years of follow-up. Since primary and secondary safety and effectiveness were in pivotal study submitted on 2012 and had been granted full approval, this meeting is mainly focusing on discussion of four aspects: transrenal stent fracture and its longer term clinical sequelae concerns; 2) Potential aneurysm enlargement over time and type I to IV endoleak; 3) graft occlusion and other patency-related events, and limb migrations; and 4) the benefit/risk profile of the device system.

Transrenal stent fracture: Approximately 10% subjects have been identified with at least one transrenal stent fracture, 3.7% with multiple fractures. It is not clear which population will develop fractures and not clear the longer term clinical implications of fractures.

 

Endoleaks: About 8% type 1a endoleak and over 50% Type II endoleak were identified. The overall endoleaks rate for the INSPIRATION study was similar with that for other commercially available devices.

Aneurysm expansion: Of 189 patients, 15% (29) of subjects experienced Aneurysm expansion in the study to date. Total 25 of 29 these aneurysm expansions, accounting for 86.21%, were deemed likely attributable to Type II endoleaks. Of the 101 patients with a Type II endoleak, 25% suffered from aneurysm expansion. This indicates a failure to halt disease progression.

Occlusions and Patency-Related Events: In the study to-date, 12.6% patients were observed with an occlusion or other patency-related events. Secondary interventions resolved stent-graft occlusions but not for other event /stenosis.

 

The INSPIRATION study found a near 80% survival rate with zero aneurysm ruptures after four years of following up, Endpoint targets were met by the study, other clinical outcomes were consistency with similar commercial devices in the market. The device is currently commercially available in 34 countries.

The board vote was overwhelming, but not unanimous, that the treatment was both safe and efficacious, so it seems that the board was more convinced of efficacy than it was of safety.