Adagio Medical Announces Positive Study Results for the vCLAS Ventricular Ablation System

Adagio Medical Holdings Inc. is reporting encouraging six-month results from its FULCRUM-VT Investigational Device Exemption (IDE) clinical trial, which will be used to support the company’s U.S. Food and Drug Administration (FDA) Premarket Approval application for the vCLAS Ventricular Ablation System.

Key findings included:

• 98% non-inducibility of targeted ventricular tachycardias (VT) at a procedure’s end
• Promising safety profile with 2.4% protocol-defined Major Adverse Events
• 84% freedom from implantable cardioverter defibrillator (ICD) shock at six months
• 59% freedom from any VT recurrence at six months (VT recurrence includes monitoring zone VT > 30 seconds, ICD shock, ATP, and anti-arrhythmic drug (AAD) escalation¹)
• Equivalent results for ischemic (ICM) and non-ischemic cardiomyopathy (NICM) patients
• More than 80% reduction in the number of patients experiencing ICD shock over six-months post ablation compared to the equivalent time period pre-ablation
• 72% of patients discontinued or reduced dose of amiodarone at six months
• Low 1.9% rate of 30-day VT-related hospital readmission

“FULCRUM-VT represents a seminal step forward in advancing ventricular tachycardia management by delivering positive, clinically meaningful results from the first large-scale, rigorously executed pivotal trial in patients with both ischemic and non-ischemic structural heart disease. Importantly, the study further highlights the potential of an endocardial-only approach using Adagio’s purpose-built ventricular ablation technology,” said Dr. Atul Verma, director, Division of Cardiology at McGill University Health Centre in Montreal. “The results of the trial, which were consistent with earlier ULTA studies, combined an excellent safety profile with impressive clinical effectiveness, including reductions in both ICD shocks and the use of toxic antiarrhythmic medication—outcomes that matter most to patients and physicians managing this complex disease. Additionally, the ability to ablate these already compromised patients without ever needing to irrigate or use nitroglycerin, both of which carry added risk, is a real benefit of ULTA. The FULCRUM-VT results are quite encouraging for the broad use of this technology as a long-term solution for patients suffering from VT.”

FULCRUM-VT (Feasibility of Ultra-Low Temperature Cryoablation in Recurring Monomorphic Ventricular Tachycardia) is a prospective, multi-center, open-label, single-arm IDE study investigating the vCLAS Cryoablation System at 20 U.S. and Canadian centers. The study enrolled 209 patients with structural heart disease, whether ischemic or non-ischemic cardiomyopathy, indicated for catheter ablation of drug-refractory VT in accordance with current treatment guidelines.

FULCRUM-VT is the first and only fully enrolled IDE clinical trial for VT to include patients with both ICM and NICM disease and includes one of the most challenging patient cohorts ever treated in a VT ablation trial, according to the company. Ablation targets for VT associated with NICM disease tend to be in deeper myocardial substrate and therefore are more difficult to treat using an endocardial approach with currently approved technology. These two patient cohorts had equivalent outcomes, as measured by both freedom from VT recurrence and freedom from ICD shock, representing reportedly the first and only catheter ablation technology to show equivalent effectiveness in these distinct and historically challenging VT substrates.

“These pivotal results represent a noteworthy milestone for Adagio and validate the potential for our ULTA technology to address a significant unmet need for treating one of the most complex and challenging arrhythmias,” Adagio Medical CEO Todd Usen stated. “In the United States alone, ventricular arrhythmias account for approximately 300,000 sudden cardiac deaths each year; VT is difficult to treat, and procedures performed with current devices can be overly complex, with sub-optimal outcomes in both effectiveness and safety. However, our FULCRUM-VT study demonstrated strong clinical effectiveness with a highly favorable safety profile with our vCLAS ablation catheter. Importantly, we achieved these results without compromising catheter stability and without the added risks of irrigation or nitroglycerin, thereby supporting the potential for a more streamlined workflow and reproducible approach to VT ablation. We believe ULTA has the potential to become a foundational ablation technology for treating the ventricle and we look forward to serving the large, underserved population of patients suffering from VT.”

FULCRUM-VT included patients with both ICM and NICM disease (LVEF=35+/-10%, 34% NICM, 79% with congestive heart failure). Freedom from device intervention (ATP or shock) at six months was 61% for ICM and 63% for NICM; freedom from ICD shock at six months was 84% for ICM and 85% for NICM. Mean ablation time per patient was 54 minutes. Mean lesions per patient: 11.5 ± 6. Key safety findings included a 2.4% rate of major adverse events, including four (1.9%) peri-procedural deaths, of which two (1%) were adjudicated by an independent Clinical Events Committee as possibly related to the investigational device. All safety and VT recurrence data were adjudicated by independent Event Committees.

The study also demonstrated clinically meaningful de-escalation of amiodarone use, an important clinical goal, with a substantial proportion of patients reducing or discontinuing amiodarone therapy after their procedure. The results also showed a significant reduction in hospital readmission rates compared to those historically reported in the VT ablation literature.

“The FULCRUM-VT results are a significant clinical achievement and compare favorably against published RF (radiofrequency) benchmarks and the emerging PFA (pulsed field ablation) data for VT,” Adagio Medical Holdings Medical Director Dr. Matthew Hakimi commented. “It is the only pivotal IDE trial to show consistent endocardial-only outcomes across both ischemic and non-ischemic cardiomyopathy—and the combination of catheter stability, titratable lesion depth, and safe navigation near vulnerable structures such as the coronary arteries positions ULTA to address arguably the broadest spectrum of VT encountered in practice. FULCRUM-VT sets a new benchmark for VT ablation, and I want to commend the many physicians and their clinical coordinators for their diligent work in evaluating this novel technology.”

FULCRUM-VT enrolled 209 patients with structural heart disease of both ischemic and non-ischemic cardiomyopathy, indicated for catheter ablation of drug-refractory VT in accordance with current treatment guidelines. FULCRUM-VT six-month primary chronic effectiveness was defined as freedom from sustained monomorphic VT lasting longer than 30 seconds or VT requiring appropriate ICD device therapy, in the absence of new or an increase in antiarrhythmic drug dose beyond previously failed ablation. The study results which have not yet been reviewed or approved by the FDA, will be used to apply for FDA premarket approval for Adagio’s vCLAS Cryoablation System.

Adagio’s vCLAS Cryoablation System is commercially available for treating monomorphic VT in Europe and select other geographies, but is limited to investigational use in the United States.

Adagio is a medical device company developing and commercializing products for treating cardiac arrhythmias with its novel, proprietary, catheter-based Ultra-Low Temperature Ablation (ULTA, formerly known as ULTC) technology. ULTA creates large, durable lesions extending through the depth of both diseased and healthy cardiac tissue, all through an endocardial approach. The company is currently focused on treating ventricular arrhythmias with its purpose-built vCLAS Cryoablation System.

Reference
¹ ATP = anti-tachycardia pacing, or a painless, non-shock pacing therapy delivered by ICDs or pacemakers to terminate rapid heart rhythms. Monitor Zone is a programmed rate range where the device detects and records arrhythmias, but does not deliver active therapies like electric shocks or anti-tachycardia pacing