New Post Hoc Analysis from the HELIOS-B Phase 3 Study Shows Vutrisiran Improved Measures of Heart Structure and Function in Patients with ATTR-CM

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced results from new post hoc analyses of the HELIOS-B Phase 3 study of AMVUTTRA (vutrisiran), an RNAi therapeutic approved for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) and the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Data from cardiovascular magnetic resonance (CMR) and echocardiographic imaging as well as renal function analyses were presented at the American Heart Association (AHA) Scientific Sessions 2025 in New Orleans, Louisiana.

As a multisystem disease, ATTR-CM can impact the health and function of organs throughout the body. These analyses evaluated the effect of vutrisiran on critical measures of heart function and structure as well as kidney health, providing deeper insight into its potential impact on key organs affected by the disease.

HELIOS-B Analyses: Cardiac Structure, Function, and Amyloid Burden

In ATTR-CM, amyloid deposits in the heart lead to thickening and stiffening of the ventricles, affecting how well the heart functions and increasing the risk of heart failure and death. Advanced imaging techniques offer insights into structural and functional changes, capturing the overall burden of amyloid deposits and their impact on cardiac function.

• A CMR analysis evaluated a retrospectively identified cohort of HELIOS-B patients from the National Amyloidosis Centre in London who underwent serial CMR scans as part of their routine clinical care at baseline (N=43), Year 1 (N=39), Year 2 (N=26), and Year 3 (N=17).
  • A mixed model analysis that pooled 24- and 36-month data found that treatment with vutrisiran monotherapy was associated with nominally statistically significant and directionally favorable changes in multiple measures of cardiac structure, function, and amyloid burden, including improvements in left and right ventricular ejection fractions as well as stroke volumes and left ventricular mass, compared to placebo.
  • Treatment with vutrisiran also reduced extracellular volume (ECV), which is thought to reflect amyloid buildup in the heart. At Year 3, amyloid regression, as assessed by ECV, was observed in 22% of patients treated with vutrisiran, while no patients who received placebo showed regression; conversely, progression occurred in 63% of patients who received placebo compared to 11% of patients treated with vutrisiran.
  • At Year 3, patients treated with vutrisiran exhibited an absolute mean (standard deviation) reduction in ECV of -0.10% (± 4.72) versus an increase of 7.86% (± 5.67) in the placebo group (p=0.006).
• To further assess cardiac function in patients with ATTR-CM, echocardiographic parameters including left atrial strain (LAS) and right ventricular free wall strain (RVFWS) were evaluated in analyses of the overall HELIOS-B population.
  • The LAS analysis demonstrated that measures of LAS were associated with baseline disease severity, mortality, and cardiovascular (CV) events, and that patients treated with vutrisiran experienced less worsening in LAS at 30 months, compared to those receiving placebo.
  • The RVFWS analysis showed that worse RVFWS was associated with higher risk of adverse outcomes and that treatment with vutrisiran stabilized RVFWS at 30 months, compared to placebo.

“As ATTR-CM progressively damages the heart muscle, making it thicker, stiffer, and less capable of pumping blood effectively, patients experience worsening symptoms, quality of life, and outcomes,” said Marianna Fontana, M.D., Ph.D., HELIOS-B investigator, Professor of Cardiology, University College London, National Amyloidosis Center, Royal Free Hospital, London. “The HELIOS-B CMR analysis provides compelling initial evidence that treatment with vutrisiran can counteract these changes in some patients, as shown by favorable impacts on measures of cardiac structure and function as well as regression of amyloid burden. These results suggest that vutrisiran has the potential not only to slow disease progression, but to reverse some of the structural damage caused by amyloid deposition in the heart in some patients.”