October 10, 2023 — Axon Therapies, a private company focused on addressing a root cause of heart failure, announced 6-month results of the REBALANCE-HF randomized, blinded feasibility trial of the Splanchnic Ablation for Volume Management (SAVM) procedure for heart failure with preserved ejection fraction (HFpEF). The main objectives of the feasibility study were to demonstrate safety, evaluate the ease and repeatable nature of the procedure, and identify the subtype of patients most likely to respond to the therapy to inform future clinical trials. While there was no improvement with the SAVM procedure compared to a control sham procedure in the full study cohort, preliminary results identified HFpEF patients who are sensitive to acute shifts in blood volume during exercise or stress were more likely to be responsive to SAVM. The responder group, which made up more than half of the full cohort, saw clinically meaningful improvements in functional capacity, symptoms and quality of life metrics at 6 months after treatment with SAVM. The results were presented by Marat Fudim, MD, MHS, Advanced Heart Failure Specialist at Duke University Medical Center, during the Late Breaking Clinical Trials session at the Heart Failure Society of America's (HFSA) Annual Scientific Meeting in Cleveland, OH.
"SAVM utilizes a novel mechanism of action for treating heart failure, so we designed the REBALANCE-HF early feasibility trial to enable us to identify potential responder groups from a broad range of HFpEF patients. These results show that HFpEF patients who are able to augment cardiac output during exertion and those without advanced structural heart disease may benefit most from SAVM," explained Sanjiv Shah, MD, Principal Investigator for the REBALANCE-HF early feasibility trial, and Advanced Heart Failure Specialist and Director of Research, Bluhm Cardiovascular Institute at Northwestern University Feinberg School of Medicine.
An overactive sympathetic nervous system is a known root cause of heart failure and can drive shifts in blood volume from the splanchnic bed, the body's main blood reservoir, to the heart and lungs during periods of exercise or stress. SAVM is a novel, front-line interventional (transcatheter) therapy that calms the overactive sympathetic nervous system by using unilateral radiofrequency to selectively ablate the greater splanchnic nerve (GSN). The minimally invasive, implant-free procedure aims to reduce sympathetic tone, enabling targeted venodilation of the splanchnic bed to normalize blood volume in the heart and lungs and prevent congestion.
The REBALANCE-HF trial is the largest randomized controlled, blinded, feasibility device trial in patients with HFpEF to date, enrolling 116 patients from 18 sites. The full treatment arm results confirmed the SAVM procedure was safe with no difference in procedure-related adverse events compared to the sham arm. SAVM was performed quickly (53 minutes on average) and had a 98% procedural success rate. The improvements SAVM demonstrated in the responder group at 6 months were sustained in patients who have available 12-month data. Key results include:
- 13-point improvement in quality-of-life at 6 months in treatment vs. sham (p=0.02) as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) score
- 36-meter improvement in ability to walk at 6 months in treatment vs. sham (p=0.08) as measured by the 6-minute walk test
- 39% relative improvement in cardiac function (NT-proBNP measures) at 6 months in treatment vs. sham (p=0.10)
- Reduced filling pressures at 1 month as measured by peak pulmonary capillary wedge pressure (PCWP) of -4.5 mmHg (vs. peak PCWP of -1.6 mmHg for sham, p=0.10)
"The favorable hemodynamics and improvements in clinical symptoms in this responder population versus the sham group is promising. Although we need additional data to confirm the results, the easy-to-perform SAVM procedure has the potential to become a front-line interventional procedure and change how we treat HFpEF patients, a notoriously complex population that makes up at least 50% of heart failure patients," added Dr. Fudim.
"We are highly encouraged by these results and expect the full data from REBALANCE-HF to be published next year," said Chad Hoskins, President and Chief Executive Officer, Axon Therapies. "I want to thank our investigators for all their work in executing this novel approach of using a randomized feasibility study to identify which patients may benefit the most from SAVM. These data will be foundational to our efforts to bring this therapy to the patients who need it most."
For more information: www.axontherapies.com