Pharmacokinetics, Safety, and Exploratory 12-Month Clinical Follow-Up of a Novel BIOtorcin™-Coated Balloon for Femoropopliteal Artery Disease: The BRight PK Study.
Lee Bernardette Jingfei BJ, Daudu Davina D, Dwyer Isabel I, Mwipatayi Daniela Liezel DL et al.
Background/Objectives: Drug-coated balloons (DCBs) provide local antiproliferative therapy during endovascular revascularization without leaving a permanent vascular scaffold. Sirolimus is an attractive cytostatic antiproliferative agent, although its relatively low lipophilicity creates challenges for rapid arterial uptake and sustained tissue residence following balloon delivery. The BRight DCB is a novel peripheral DCB coated with BIOtorcin™ (CRC-015), a highly lipophilic synthetic derivative of sirolimus. The BRight PK study primarily evaluated the systemic pharmacokinetics of BIOtorcin™ and its metabolite sirolimus following treatment of femoropopliteal disease and secondarily assessed procedural performance, safety, patency, and functional outcomes over 12 months. Methods: BRight PK was a prospective, single-center, non-randomized pharmacokinetic study involving six adults with symptomatic peripheral artery disease (PAD; Rutherford-Becker category 2-4) caused by de novo superficial femoral and/or proximal popliteal artery disease. Following mandatory predilatation, lesions were treated with one or two BRight DCBs. Whole-blood BIOtorcin™ and sirolimus concentrations were measured before treatment and serially from 5 min to 24 h after removal of the final DCB. Non-compartmental pharmacokinetic analysis was performed. Angiography and duplex ultrasound were independently assessed by a core laboratory, and endpoint-related clinical events were independently adjudicated. Results: All six participants completed 12-month follow-up. Mean age was 70.8 ± 7.4 years, and four (66.7%) were male. Seven BRight DCBs treated six lesions. Mean core-laboratory lesion length was 140.85 ± 136.23 mm, and baseline diameter stenosis was 78.50 ± 23.39%. Mean BIOtorcin™ exposure was 3976.8 ± 1665.7 µg (0.051 ± 0.0188 mg/kg). BIOtorcin™ Cmax was 23.60 ± 9.88 ng/mL at 5 min, terminal half-life was 21.87 ± 10.17 h, AUC0-t was 28.30 ± 12.19 h·ng/mL, and AUC0-∞ was 47.47 ± 18.27 h·ng/mL. Sirolimus Cmax was 0.692 ± 0.462 ng/mL at 24 h, when concentrations remained on the ascending portion of the concentration-time curve, indicating that the 24 h sampling window captured only early systemic sirolimus exposure rather than a complete pharmacokinetic profile. Device success was 100% (7/7); core-laboratory technical and procedural success were each 66.7% (4/6). No deaths, major or minor amputations, clinically driven target lesion revascularizations (cd-TLR), or clinically driven target vessel revascularizations (cd-TVRs) occurred. Visit-based 12-month primary patency was 83.3% (5/6); the single binary restenosis was detected at day 391, resulting in Kaplan-Meier primary patency of 100% at calendar day 365. The mean overall Walking Impairment Questionnaire (WIQ) score increased from 21.87 ± 19.16 at baseline to 62.28 ± 38.78 at 12 months. Conclusions: BIOtorcin™ demonstrated rapid systemic appearance following BRight DCB treatment, followed by a progressive decline in circulating parent drug concentrations and low systemic exposure to its metabolite, sirolimus. These pharmacokinetic findings, together with successful device delivery and the absence of major safety concerns over 12 months, demonstrate procedural feasibility and support continued clinical evaluation of the BRight DCB. Given the pharmacokinetic study design and small sample size (n = 6), the 12-month clinical, functional, and patency findings are exploratory and hypothesis-generating and should not be interpreted as evidence of clinical efficacy.