Vascular surgeon Lewis Schwartz, MD, has had an interest in biomedical engineering since very early in his career. So his involvement in the early-stage Efemoral vascular scaffold system marks a significant milestone in a mission to save legs and provide better care for patients with peripheral arterial disease (PAD).
Schwartz, a clinical professor of surgery at University of Illinois College of Medicine in Park Ridge, Illinois, is one of the co-founders behind the novel, balloon-expandable, resorbable, drug-eluting device, which late last year saw results from a study in domestic farm swine delivered at the annual meeting of the Midwestern Vascular Surgical Society (MVSS) in Chicago.
The pre-clinical trial showed that “long, mobile, peripheral arteries can be successfully treated with multiple, short, balloon-expandable, bioresorbable scaffolds,” presenting author Rym El Khoury, MD, told MVSS attendees.
El Khoury—formerly a general surgery resident at University of Illinois Metropolitan Group Hospitals in Chicago and now a vascular surgery fellow at the University of California San Francisco (UCSF)—explained how the results were drawn from a total of 38 resorbable scaffolds implanted in eight iliofemoral arteries of four female swine. Configurations, she said, consisted of two scaffolds in two arteries, four scaffolds in another two arteries, six scaffolds in three arteries, and eight scaffolds in one. The total arterial scaffolded length ranged from 32–97mm.
The Efemoral system, or EVSS, being developed under the auspices of Efemoral Medical, has been heralded as a “new paradigm” in the treatment of long-segment lesions with a device made up of multiple, short scaffolds. “The EVSS is directed to the long, occlusive, atherosclerotic lesions typical of the human peripheral arterial tree and was designed to become the first absorbable stent with widespread clinical viability,” reflects Schwartz in an interview with Vascular Specialist.
It seeks to succeed where previous bioresorbable scaffolds have suffered pitfalls in five ways, he continues. “By targeting the unmet clinical needs of peripheral vascular intervention, as opposed to coronary intervention; by exhibiting the radial force typical of balloon-expandable metal stents, as opposed to self-expanding nitinol stents; by employing a co-polymer to enhance strength and ductility; by formulating the scaffold to degrade within the first two years, as opposed to the four years typical of historical absorbable stents; and by serially mounting multiple, independent scaffolds over the device length in order to mitigate fracture and facilitate the treatment of long lesions.”
Schwartz details how the design of radial strength is exhibited “like a freight train negotiating a tight bend in the tracks, the individual scaffolds maintain the arterial lumen with high radial force while the inter-scaffold spaces are free to bend and compress during limb movement.
“As such, the EVSS can readily treat the short lesions of the femoropopliteal arteries that have been traditionally enrolled in clinical trials of peripheral vascular intervention; in addition, simply by loading more scaffolds onto longer angioplasty balloons, the EVSS can be easily adapted for the treatment of long femoropopliteal lesions heretofore inaccessible using currently available technology,” Schwartz says.
‘Preserved structural integrity’
El Khoury elaborates further on the results presented at the MVSS in Chicago. “Angiographic and optical coherence tomography (OCT) images were obtained of the hindlimb in natural extension and exaggerated flexion showed that native porcine iliofemoral arteries significantly deformed with passive hindlimb flexion as expected (bending 110±20° and compression 20±14%) while preserving their mean luminal diameter even with extreme deformation (4.7±0.4mm vs. 5.0±0.2mm in extension vs. flexion; p=0.16),” she tells Vascular Specialist.
“Following EVSS implantation, supra-physiologic flexion created similar patterns of deformation in the treated artery (bending 113±19° and compression 15±15%) while mean luminal diameter remained stable without kinks or occlusion (4.7±0.7mm vs. 4.7±0.5mm in extension vs. flexion; p=0.80). Arterial deformation was borne by shortening of the inter-scaffold spaces (2.2±08mm vs. 1.9±0.7mm in extension vs. flexion; p<0.01) as well as the scaffolds themselves (10.7±1.4 vs. 9.9±1.1mm in extension vs. flexion; p<0.01). OCT and 3D micro-computed tomography (micro-CT) imaging confirmed consistent wall apposition and preserved structural integrity in all scaffolds,” El Khoury further explained.
The first-in-human EFEMORAL I trial, meanwhile, is a prospective, single-arm, open-labeled, multicenter, clinical investigation enrolling patients with an arterial diameter of ≥5.5mm and ≤6.5mm, and lesion length ≤90mm receiving a single EVSS, Schwartz details. Its purpose is to evaluate safety and performance of the sirolimus-eluting EVSS in patients with symptomatic peripheral arterial occlusive disease from stenosis or occlusion of the femoropopliteal or external iliac artery. The principal investigator is Andrew Holden, MDChB, director of interventional radiology at Auckland City Hospital, Auckland, New Zealand. The trial has a primary safety endpoint of freedom from major adverse events at 30 days and a primary efficacy endpoint of freedom from binary restenosis at 12 months.
Also of note, Schwartz explains, is that the EVSS was originally formulated with paclitaxel as the anti-proliferative agent of choice. However, after the 2018 meta-analysis by Konstantinos Katsanos, MD, et al suggested the drug “carries an increased risk of late mortality […] Efemoral felt it prudent to abandon the cytotoxic drug paclitaxel in favor of the cytostatic drug sirolimus.”
Schwartz reiterates his drive to tackle “the unmet clinical need for effective lower-extremity revascularization.” With the historical strategy of open surgical bypass, he says, some “14–44% of long bypass leg incisions become infected and up to 69% of patients are re-hospitalized in the first year, with excessive mortality and morbidity.” Yet, while “the current paradigms” of endovascular therapy—such as employing balloon dilatation and dilatation with specialty balloons coated with antiproliferative drugs—are generally effective in treating short lesions, Schwartz continues, “the results of endovascular intervention in the long, chronic occlusions observed in critically ischemic patients remain dismal.”
Combating leg amputation
Schwartz says the EVSS design and development have been informed by a long career that has included early training in biomedical engineering, general and vascular surgery, a decade of academic basic and clinical investigation, and a decade of designing and developing biomedical device intravascular strategies, in addition to “a tragic but lifelong experience of leg amputation.”
Improvements in the treatment of PAD over the last near half century “have been quantum” but failure, including extremity amputation, “remains commonplace,” he says. “We can do better.” For now, Schwartz adds, the device holds promise. “Assuming consistent demonstration of the safety and efficacy of the EVSS in pre-clinical and clinical investigations, the device could potentially become commercially available in the U.S. as early as 2027.”
