Development of a balloon angioplasty catheter capable of simultaneous endovascular delivery of liquid therapeutic agents into the vascular wall

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PROJECT SUMMARY Lower extremity peripheral artery disease (PAD), caused by the buildup of plaque in the leg arteries, affects approximately 10% of the American population. In severe cases, this obstruction of normal blood flow in the legs can cause limb-threatening ischemia. Severe PAD typically requires surgical intervention consisting of angioplasty, vascular stenting, endarterectomy, or arterial bypass. The most common failure mode of endovascular arterial interventions for PAD is intimal hyperplasia, a hypertrophic response to vascular reconstructive procedures that leads to restenosis and the return of vascular insufficiency symptoms. Until recently, the primary tools for combating intimal hyperplasia following surgical intervention were paclitaxel-coated intraluminal drug-eluting stents and balloons. However, the use of paclitaxel-coated devices was associated with an increased risk of death compared to uncoated devices, and the FDA issued a recommendation to halt the use of all paclitaxel-coated devices for PAD in 2019. Similarly, the FDA-approved drug sirolimus has been shown to be safe and effective in preventing restenosis in coronary artery lesions; however, sirolimus-coated stents are associated with an increased risk of vascular thrombosis. As a result, there is an unmet need for safer endovascular delivery devices to combat intimal hyperplasia following PAD treatment. StemPlant LLC is developing a novel device platform, the Peripheral Vascular Angioplasty Delivery Device (PVADD), to directly deliver sirolimus, and possibly other follow-on therapeutics, into the subintimal space of peripheral arteries. The PVADD, based on the standard Percutaneous Transluminal Angioplasty balloon catheter, incorporates unique tubular fluid paths peripherally around the balloon with distal port geometry designed to deliver liquid therapeutics directly into the arterial wall during balloon inflation. Using a swine model, we have previously demonstrated the efficacy of this device in successfully delivering cells to the subintimal area without injuring or destroying the artery. In this Phase I SBIR, StemPlant proposes to develop a PVADD that can be paired with sirolimus for treatment of intimal hyperplasia and prevention of restenosis. They will accomplish this by (1) establishing a fully integrated prototype for delivering liquid therapeutic directly to the peripheral artery vasculature in compliance with FDA guidance, (2) evaluating the feasibility of endovascular delivery of a liquid drug in vivo using a swine model and Fluorescite® as a proxy for sirolimus, and (3) achieving a final device design in preparation for validation builds. Completion of the proposed SBIR Phase I program will position StemPlant for a statistically powered Phase II study in a large animal intimal hyperplasia model to quantify sirolimus delivery and assess efficacy of the sirolimus PVADD to treat intimal hyperplasia.