Anteris Technologies Pty Ltd (ASX:AVR, NASDAQ:AVR) has received regulatory clearance from the Danish Medicines Agency to begin its global pivotal trial of the DurAVR® transcatheter heart valve (THV) in patients with severe calcific aortic stenosis.
The company said patient enrolment at Danish centres is expected to start in the fourth quarter of 2025. Denmark is the first country to authorise participation in the study, dubbed PARADIGM — a prospective, randomised controlled trial comparing DurAVR against commercially available transcatheter aortic valve replacement (TAVR) devices.
Anteris plans to broaden the trial footprint “in the near term” with additional sites across the United States, Europe and Canada. The company noted strong investigator interest and expects this to support efficient recruitment.
In the US, an Investigational Device Exemption (IDE) application remains under review by the Food and Drug Administration. Anteris said it continues to anticipate near-term IDE approval, which would allow US sites to initiate following Institutional Review Board clearance.
“The PARADIGM trial is a multi-centre global study which, if successful, will result in multiple approvals and labels for the DurAVR® THV,” vice chairman and CEO Wayne Paterson said.
“This is a watershed moment in the company’s lifecycle and marks the beginning of the commercialisation planning phase as we march towards global approvals. Anteris is excited to be able to allow access to an increasing pool of patients globally who will benefit from this life-saving technology. The commencement of this trial reflects the commitment and tireless work of our talented Anteris team, as well as our physician and scientific advisors. The company would like to express its gratitude to the physicians, patients and shareholders who have been fundamental in developing this important new therapy.”
Trial design and endpoints
PARADIGM will enrol about 1,000 “all-comers” who will be randomised 1:1 to receive either DurAVR THV or a currently approved TAVR. The study is powered for non-inferiority on a composite primary endpoint at one year comprising all-cause mortality, all stroke and cardiovascular hospitalisation.
Further cohorts and geographic expansion are planned as the study progresses. Additional protocol details are available on ClinicalTrials.gov.
“Receiving initial approval in Europe is an important milestone as it signals the launch of the global PARADIGM Trial. This groundbreaking study has been designed with world-leading experts and is attracting significant interest from clinicians globally, reflecting the potential for DurAVR® to transform care for patients with aortic stenosis,” Anteris chief medical officer Chris Meduri MD said.
“The PARADIGM Trial enables us to bring promising new technology to patients across all surgical risk groups, building on the growing body of evidence supporting the DurAVR® THV’s favourable hemodynamic performance. We look forward to contributing meaningful data which could support both PMA* and CE Mark approvals,” said Dr. Michael Reardon and Professor Stephan Windecker, study co-chairs of the global PARADIGM Trial.
Regulatory pathway
Data from PARADIGM are intended to support a US premarket approval (PMA) submission. PMA typically requires high-level clinical evidence; randomised controlled trials are considered the gold standard for demonstrating safety and effectiveness.
*A Premarket Approval (PMA) application requires a high level of clinical evidence to demonstrate reasonable assurance of safety and effectiveness for the intended use. Randomised controlled trials are generally considered Level 1 evidence, the highest level for determining the effectiveness of interventions in evidence-based medicine given RCTs mimimise bias and allow a clear comparison between treatment groups.