A retrospective post hoc analysis of the HELIOS-B trial published in JAMA Cardiology shows vutrisiran treatment is associated with favorable cardiac magnetic resonance parameters and amyloid regression in transthyretin amyloid cardiomyopathy patients.
New imaging evaluations and long-term trial updates are shedding light on how targeted therapies alter the course of transthyretin amyloid cardiomyopathy (ATTR-CM). Recent data published in JAMA Cardiology reveal that vutrisiran treatment correlates with significant positive shifts in cardiac structure, function, and amyloid burden.
Imaging Insights From the HELIOS-B Trial Analysis
The retrospective post hoc analysis evaluated 43 participants with a mean age of 75 years, 95% of whom were male. All patients underwent baseline cardiac magnetic resonance (CMR) imaging. Follow-up scans occurred at one, two, and three years for subsets of 39, 26, and 17 patients, respectively. Baseline parameters were comparable between treatment and placebo arms.
Patients receiving vutrisiran demonstrated measurable improvements across multiple metrics of cardiac performance. The biventricular ejection fractions showed a least-squares mean difference of 19% for the left ventricle and 16% for the right ventricle. Stroke volumes increased notably in both chambers.
Evidence of Amyloid Regression and Mass Reduction
Beyond functional improvements, the CMR imaging tracked direct changes in tissue characteristics. Researchers defined amyloid regression and progression as absolute reductions or increases in extracellular volume (ECV) of 5% or more.
By the three-year follow-up mark, 22% of patients taking vutrisiran exhibited amyloid regression, whereas zero patients in the placebo group experienced regression. Conversely, 63% of placebo recipients experienced amyloid progression, compared to only 11% of patients in the vutrisiran cohort.
“The observation of amyloid regression in a subset of patients who received vutrisiran…supports the hypothesis that effective, sustained suppression of TTR production can shift equilibrium between amyloidogenesis and clearance, permitting disease modification and net reduction in myocardial amyloid.”
Yousuf Razvi, MBChB, BSc, et al., via ACC
Additionally, vutrisiran treatment was associated with a reduction in left ventricular mass and a decrease in extracellular volume.
Long-Term Follow-Up and Trial Oversight for Cliramitug
Parallel developments in the therapeutic landscape include long-term data from the NI006-101 trial investigating cliramitug. Conducted across six sites in Germany, France, Spain, and the Netherlands, the proof-of-concept study operated in compliance with Good Clinical Practice guidelines and the Declaration of Helsinki.
The trial protocol secured approval from pertinent national regulatory authorities, including the Paul-Ehrlich Institut in Germany, the Agence nationale de sécurité du médicament et des produits de santé in France, the Agencia Española de Medicamentos y Productos Sanitarios in Spain, and the Centrale Commissie Mensgebonden Onderzoek in the Netherlands. Local ethics committees also granted authorization before participant enrollment.
Protocol Adjustments and Safety Assessments in Outpatient Settings
Initial trial progress faced recruitment delays driven largely by the COVID-19 pandemic, which prevented early-enrolled participants from being up-titrated to expected efficacious doses. To generate robust safety and efficacy data at a dose level of 30 mg kg−1, investigators amended the protocol to extend the original open-label extension.
These adaptations, categorized as OLE2, permitted 6 to 12 additional administrations of cliramitug depending on the starting dose level, bringing the maximal infusion count up to 24. All OLE2 participants received the study drug via intravenous infusion over roughly 50 to 60 minutes in an outpatient setting. Assessments of safety, local laboratory results, vital signs, and echocardiography parameters continued throughout the extended timeline.
