PERCUTANEOUS TREATMENT OF PERIPHERAL ARTERIAL OCCLUSIVE DISEASE WITH IMPLANTATION OF MULTIPLE, BALLOON-EXPANDABLE, DRUG-ELUTING BIORESORBABLE SCAFFOLDS (the Efemoral Vascular Scaffold System)

Cardiovascular disease is a tremendous burden on human health and longevity; by the year 2030, over 400million people will have the disease including an annual mortality of more than 23 million. Vascular diseaseaffecting the lower extremity arteries, known as “peripheral arterial occlusive disease” (PAOD), is an epidemicaffecting approximately 10% of the population over the age of 50 and 20% of the population over the age of 70.Its prevalence is increasing at an alarming rate, by more than 20% over the last decade. Symptomatic PAODcauses loss of mobility, poor physical health, decreased quality of life, premature decline and early mortality.The physical burden of PAOD is greater than having congestive heart failure and the long-term prognosis isworse than having coronary artery disease. An estimated 11% of patients afflicted with PAOD have the mostsevere form of the disease: critical limb ischemia (CLI). CLI occurs when the occlusive lesions of PAOD havebecome so numerous and severe that the baseline perfusion of the extremity is inadequate to sustain itsviability. It carries a dismal prognosis; only about half of affected patients will be alive with viable limbs only sixmonths after the diagnosis is made. The standard-of-care for patients with symptomatic PAOD is percutaneous peripheral intervention (PPI)including the techniques of balloon angioplasty, drug-coated balloon angioplasty, percutaneous atherectomy,and bare and drug-eluting self-expanding stenting. Unfortunately, the effectiveness and durability of availabledevices is limited as up to 50% of conventional endovascular procedures will be complicated by arterialrestenosis and recurrence within the first year. This research proposal describes the development of novel,serial, balloon-expandable, resorbable, drug-eluting scaffold designed to provide more immediately effectiveand durable endovascular treatment of symptomatic femoropopliteal occlusive disease. Unlike most peripheral intravascular devices that are simply adaptations and “scale-ups” of coronarydevices, the Efemoral Vascular Scaffold System (EVSS) is specifically designed for the unique environment ofthe peripheral vasculature. Its design exploits known principles of vascular biology including that, (1) a rigiddevice that is deployed via balloon expansion represents the optimal design of an intravascular stent given itstransient effect on the arterial wall and relative ease of precise implantation, (2) a long, rigid device cannot besafely implanted in an artery that bends and twists with skeletal motion, (3) long arteries that bend and twistcould be effectively treated with multiple, short stents that allow the intervening, non-stented arterial segmentsto move unencumbered, (4) the length, number and spacing of the stent segments could be determined by theknown bending characteristics of the target arteries, and (5) arteries need only be scaffolded transiently; latedissolution of the stent will facilitate long-term arterial healing and avoid the late complications of an indwellingforeign body. Efemoral Medical, Inc., was founded in 2015 with the mission of developing a novel, balloon expandable, resorbable, drug-eluting scaffold designed to provide more simple, effective and durableendovascular treatment of symptomatic femoropopliteal occlusive disease. The Efemoral Vascular ScaffoldSystem (EVSS) is a cheap and easily-manufactured biocompatible device that is prepared and deployed in anidentical manner to simple angioplasty balloons. Private funding from vascular surgeons, interventionalradiologists, interventional cardiologists, independent investors, friends and family established EfemoralMedical, Inc. as a going concern and developed the device through its design, prototype, biochemical,mechanical, toxicologic and pre-clinical proof-of-concept phases. A first-in-human, early feasibility,international clinical trial has enrolled six patients with good results. The purpose of this Direct Phase II SBIR proposal is to demonstrate the pre-clinical safety and efficacy ofthe Efemoral Vascular Scaffold System (EVSS) in preparation for initiation of a clinical Early Feasibility Study(EFS) in the United States. It’s Specific Aims are, (1) To demonstrate long-term device safety and efficacy in aGLP pre-clinical model of percutaneous peripheral vascular intervention, (2) To quantify device elution, muraldrug transfer, systemic exposure and pharmacokinetic profile in a GLP pre-clinical model of percutaneousperipheral vascular intervention, and (3) To quantify the kinetics of scaffold dissolution in a GLP pre-clinicalmodel of percutaneous peripheral vascular intervention.