Orchestra BioMed Holdings has announced that the US Food and Drug Administration (FDA) has approved its investigational device exemption (IDE) amendment to initiate an updated design of the company’s planned Virtue trial.
The IDE provides FDA regulatory clearance for Orchestra BioMed to initiate a US pivotal clinical trial comparing its Sirolimus-AngioInfusion balloon—Virtue SAB—to the Agent (Boston Scientific) paclitaxel-coated balloon, currently the only drug-coated balloon (DCB) carrying an FDA approval for a coronary indication. Data from the Virtue trial will be used to support regulatory approval in the USA.
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, Orchestra BoiMed details in a press release. SirolimusEFR enables tissue uptake and extended release of the required therapeutic levels of sirolimus (> 1ng/mg tissue concentration).
Virtue SAB has been previously granted FDA breakthrough device designation for the treatment of coronary in-stent restenosis (ISR) as well as for coronary small vessel disease and peripheral artery disease below-the-knee.
In the multicentre 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 six-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 (The Christ Hospital Heart & Vascular Institute, Cincinnati, USA), co-principal investigator on the Virtue trial.
“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,” comments Allen Jeremias (St Francis Hospital & Heart Center, Flower Hill, USA), who is also a co-principal investigator on the trial. “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.
“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.”
“We believe there is a multibillion-dollar US 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.”
The Virtue Trial is a prospective, multicentre, 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, non-fatal target vessel myocardial infarction (MI) and ischaemia-driven target lesion revascularisation at 12 months.
The trial will randomise 740 patients across up to 75 centres in the USA. 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.
