Orchestra BioMed Holdings, a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships, has announced that FDA has approved its Investigational Device Exemption amendment to initiate an updated design of the Company’s planned Virtue SAB in the Treatment of Coronary ISR Trial.
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The IDE provides FDA regulatory clearance for Orchestra BioMed to initiate a U.S. pivotal clinical trial comparing its highly differentiated, next-generation Sirolimus-AngioInfusion Balloon, Virtue SAB to the Boston Scientific AGENT paclitaxel-coated balloon, currently the only drug-coated balloon (“DCB”) FDA-approved for a coronary indication. Data from the Virtue Trial will be used to support regulatory approval in the U.S. Virtue SAB and SirolimusEFR are investigational technologies owned by Orchestra BioMed, which also controls and is responsible for all regulatory filings, clinical operations, and drug and device supplies for the Virtue Trial.
The differentiation of Virtue SAB, an FDA breakthrough designated device
Virtue SAB is designed to deliver a proprietary extended-release formulation of sirolimus, SirolimusEFR, through a non-coated microporous AngioInfusion Balloon that protects the drug in transit to consistently deliver a large liquid dose, overcoming certain limitations of DCBs. SirolimusEFR enables tissue uptake and extended release of the required therapeutic levels of sirolimus (> 1ng/mg tissue concentration), the “gold-standard” drug for preventing arterial restenosis, through the critical healing period of approximately 30 days. Virtue SAB has been previously granted FDA Breakthrough Device Designation for the treatment of coronary ISR as well as for coronary small vessel disease and peripheral artery disease below-the-knee. In the multi-center SABRE pilot study, Virtue SAB demonstrated best-in-class clinical results for the treatment of coronary ISR, including 12-month target lesion failure of 2.8% and 6-month late lumen loss of 0.12mm.
“Virtue SAB has the potential to be one of the most compelling technologies in interventional cardiology. It’s the only product in development that optimises both the arterial tissue uptake and retention of sirolimus to achieve pharmacokinetics that match or even exceed those of proven ‘limus-eluting stents,” said Dean J. Kereiakes, M.D., FACC, MSCAI, chairman of The Christ Hospital Heart & Vascular Institute, medical director of The Christ Hospital Research Institute, Professor of Clinical Medicine at The Ohio State University, Professor of Medicine at University of Cincinnati and Co-Principal Investigator on the Virtue Trial.
Dr. Kereiakes continued: “Virtue SAB is designed to consistently deliver a large liquid dose of an extended-release formulation of sirolimus to overcome certain limitations of traditional DCBs, including lower doses due to surface area and coating integrity constraints, drug loss in transit leading to inconsistent dosing, and the risk of emboli from large coating particulates. As the coronary treatment landscape continues to shift toward more rapid adoption of DCBs, I’m excited about the potential of Virtue SAB to set a new standard of care.”
“Drug-coated balloons are emerging as a new standard of care in the treatment of various coronary and peripheral indications, and I believe utilisation of this class of technology will continue to grow and evolve over time as the science is expanding. In a field largely reliant on paclitaxel drug-coated balloons, Virtue SAB stands out as the only device with a completely different mechanism of action; namely to provide delivery of a large liquid dose of an extended-release formulation sirolimus," commented Allen Jeremias, MD, MSc, associate director of the Cardiac Catheterization Laboratory at St. Francis Hospital & Heart Center, and co-principal investigator on the Virtue Trial. “Having had the opportunity to work with several DCBs, I anticipate continued momentum for this class, and am eager to see how Virtue SAB, particularly with its anti-restenotic, anti-inflammatory and cytostatic SirolimusEFR formulation, performs in a head-to-head trial against a paclitaxel-coated balloon.”
Showcasing distinctive and sustainable advantages of Virtue SAB through a head-to-head trial
“We believe there is a multibillion-dollar U.S. market for coronary drug delivery balloons based on the significant unmet clinical need, market demand, and established reimbursement,” said David Hochman, chairman and chief executive officer of Orchestra BioMed. “We made a deliberate, strategic decision to pursue a head-to-head trial with the commercially available AGENT paclitaxel-coated balloon, underscoring our confidence in Virtue SAB as a fundamentally differentiated solution for the treatment of atherosclerosis. We believe this approach offers the most direct path to regulatory approval while also providing the best opportunity to demonstrate what we believe are distinctive and sustainable advantages of our proprietary technology.”
Mr. Hochman continued, “The superior safety and efficacy of sirolimus over paclitaxel was made clear by the performance of drug-eluting stents. Published meta-analysis involving 76 trials show ‘limus-eluting stents have significantly better clinical performance than paclitaxel-eluting stents in terms of target lesion revascularisation and major adverse cardiac events. We believe this is due to their ability to maintain sufficient drug tissue concentration through the critical healing period of approximately 30 days, because stents that failed to do this did not perform well clinically. Virtue SAB is the only drug delivery balloon that has demonstrated comparable drug tissue levels to clinically successful drug-eluting stents in large published preclinical studies, without the need to leave a permanent metal implant in the artery. Our pilot clinical results with Virtue SAB also highlight the potential for optimal clinical outcomes with robust sirolimus delivery. We’re excited to showcase the full potential of Virtue SAB in this landmark trial and are proud of our team and grateful to our clinical collaborators for their work in achieving this important milestone.”
The Virtue Trial is a prospective, multi-centre, randomised trial comparing clinical outcomes of Virtue SAB to AGENT Paclitaxel DCB in the treatment of coronary ISR, a difficult-to-treat and serious complication of coronary stenting. 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 revascularisation at 12 months. The trial will randomise 740 patients across up to 75 centres in the US. With the amended IDE approved by the FDA, Orchestra BioMed is currently targeting initiation of the Virtue Trial during the second half of 2025, bringing the Company one step closer to delivering a next-generation solution for atherosclerotic disease.