Orchestra BioMed has achieved a significant milestone in cardiovascular device development with the enrollment of first patients in the Virtue Trial, a pivotal U.S. investigational device exemption study evaluating its innovative Virtue® Sirolimus AngioInfusion™ Balloon (Virtue SAB) against the currently approved AGENT paclitaxel-coated balloon for treating coronary in-stent restenosis.
The initial cases were successfully completed at The Christ Hospital Heart & Vascular Institute in Cincinnati, OH, and St. Francis Hospital & Heart Center in Roslyn, NY, marking the official launch of this head-to-head randomized trial designed to support regulatory approval in the United States.
Revolutionary Drug Delivery Technology
Virtue SAB represents a paradigm shift in balloon-based drug delivery, utilizing a patented non-coated microporous AngioInfusion™ Balloon to deliver large liquid doses of proprietary extended-release sirolimus (SirolimusEFR™). This approach is designed to overcome key limitations of traditional drug-coated balloons, including dosing constraints, drug loss during navigation, and release of embolic particulates.
"Virtue SAB and SirolimusEFR were specifically designed to optimize the dose, delivery, uptake and extended release of sirolimus without the limitations of a drug coating on the balloon surface," said Dr. Jarrod D. Frizzell, Director of Complex Coronary Therapeutics at The Christ Hospital Health Network. "A substantial body of clinical evidence from drug-eluting stent studies has established sirolimus and its analogs as the gold-standard drug for promoting vessel healing and preventing restenosis following interventional procedures."
The SirolimusEFR formulation is engineered to enable enhanced tissue uptake and extended release of therapeutic levels of sirolimus through the critical healing period, exceeding previously published target tissue concentrations of proven drug-eluting stents.
Addressing a Significant Clinical Need
Coronary in-stent restenosis represents a serious complication of coronary stenting that increases the risk of life-threatening heart problems. According to the National Cardiovascular Data Registry, coronary ISR occurs in up to 10% of stented patients during the first year and continues at a rate of up to 3% per year thereafter, resulting in an estimated over 325,000 coronary ISR lesions annually worldwide that may require treatment.
If left untreated, coronary ISR may lead to stable angina, unstable angina, acute coronary syndrome, acute myocardial infarction, or death. The condition affects an estimated 100,000 patients in the U.S. annually, representing a significant unmet medical need.
Promising Pilot Study Results
In the multi-center SABRE pilot study, Virtue SAB demonstrated encouraging clinical outcomes for the treatment of single-layer coronary ISR, achieving a 12-month target lesion failure rate of just 2.8%, zero target lesion revascularizations from 12-month follow-up through 36-month follow-up, and 6-month late lumen loss of only 0.12mm.
Dr. Allen Jeremias, Director of Interventional Cardiology Research at St. Francis Hospital & Heart Center and co-principal investigator of the Virtue Trial, commented: "Drug coated balloons offer a promising alternative to drug-eluting stents for the treatment of coronary indications such as coronary ISR. Virtue SAB and SirolimusEFR are designed to go beyond DCBs with the goal of optimizing drug dosing, tissue uptake and extended drug bioavailability at the site of treatment."
Trial Design and Regulatory Pathway
The Virtue Trial is a prospective, multi-center, randomized trial comparing clinical outcomes of Virtue SAB to AGENT Paclitaxel DCB in the treatment of coronary ISR. The study is expected to randomize 740 patients across up to 75 centers in the United States, with enrollment completion currently planned for mid-2027.
The primary endpoint is a non-inferiority comparison of Target Lesion Failure (TLF) defined as a composite of cardiac death, nonfatal target vessel myocardial infarction and ischemia-driven target lesion revascularization at 12 months. Data from the Virtue Trial is expected to support regulatory approval in the U.S.
Virtue SAB has received FDA Breakthrough Device Designation for the treatment of coronary ISR, as well as for coronary small vessel disease and below-the-knee peripheral artery disease, highlighting the regulatory agency's recognition of its potential to address significant unmet medical needs.
Market Opportunity and Strategic Vision
Orchestra BioMed estimates the total global market opportunity for drug-eluting balloons to be over $10 billion annually. Darren R. Sherman, President and Chief Operating Officer of Orchestra BioMed, stated: "We believe the future of arterial disease treatment will be driven by optimized delivery and extended tissue release of therapeutic doses of sirolimus, the proven antiproliferative drug with well-established safety and effectiveness."
Sherman emphasized the company's strategic approach: "We designed Virtue SAB and its key enabling technology, our proprietary SirolimusEFR, to overcome these limitations and realize the full potential of arterial drug delivery during angioplasty. With the launch of the Virtue Trial, we're taking a major step toward realizing our vision of improving patient outcomes."
The successful initiation of the Virtue Trial represents a critical milestone for Orchestra BioMed as it advances its innovative approach to treating atherosclerotic artery disease, the leading cause of mortality worldwide.
