Vutrisiran Improves Cardiac Structure and Function in ATTR-CM Patients: New Post Hoc Analysis of HELIOS-B Phase 3 Trial

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11/08/2025 – 04:57 PM

− Analyses Presented at the American Heart Association Scientific Sessions 2025 Underscore Vutrisiran’s Differentiated Profile –

− Cardiovascular Magnetic Resonance (CMR) and Echocardiographic Analyses Demonstrate that Treatment with Vutrisiran Resulted in Significant Changes on Multiple Functional and Structural Cardiac Parameters –

– In a Cohort of HELIOS-B Patients, CMR Imaging Showed Amyloid Regression in 22% of Vutrisiran Treated Patients with No Regression Found in Patients Who Received Placebo –

– Treatment with Vutrisiran Preserved Kidney Function in HELIOS-B Patients, and Reduced Risk of Death and Cardiovascular Events in Patients with Advanced Chronic Kidney Disease –

CAMBRIDGE, Mass. — Alnylam Pharmaceuticals (ALNY), a leader in RNAi therapeutics, presented compelling new data at the American Heart Association (AHA) Scientific Sessions 2025. These findings, derived from post-hoc analyses of the Phase 3 HELIOS-B study, spotlight the therapeutic potential of AMVUTTRA (vutrisiran) in managing transthyretin-mediated amyloidosis cardiomyopathy (ATTR-CM). Vutrisiran is already approved for both ATTR-CM and hereditary transthyretin-mediated amyloidosis polyneuropathy (hATTR-PN) in adults, making these new insights particularly significant.

The presented data, scrutinizing cardiovascular magnetic resonance (CMR) and echocardiographic imaging, alongside renal function analyses, provide a nuanced understanding of vutrisiran’s impact on the multifaceted nature of ATTR-CM, which affects various organ systems.

HELIOS-B Deep Dive: Structural and Functional Cardiac Improvements

ATTR-CM is characterized by amyloid deposits within the heart, leading to ventricular thickening and impaired cardiac function, ultimately escalating the risk of heart failure and mortality. The new analyses employed advanced imaging techniques to evaluate the changes in cardiac structure and function under vutrisiran treatment.

• One notable CMR analysis focused on a retrospective cohort from the National Amyloidosis Centre in London (N=43 at baseline), illustrating the results from routine CMR scans over three years.
  • The findings revealed that vutrisiran monotherapy was associated with statistically significant and favorable changes in key cardiac parameters. There were statistically notable improvements in left and right ventricular ejection fractions, stroke volumes, and left ventricular mass compared to the placebo group. This signals a potential for enhanced cardiac output and reduced strain on the heart.

  • Crucially, vutrisiran treatment also appeared to reduce extracellular volume (ECV) – a key indicator of amyloid buildup in the heart. By Year 3, 22% of vutrisiran-treated patients exhibited amyloid regression (as measured by ECV), while none in the placebo group showed similar improvement. Simultaneously, amyloid progression was significantly lower in the vutrisiran group (11%) compared to the placebo group (63%). This is of particular interest to investors as it provides the first evidence that this class of drugs leads to actual amyloid regression in a significant proportion of patients.

  • Quantitative data at Year 3 further emphasized this trend, with vutrisiran patients showing an absolute mean reduction in ECV of -0.10% (± 4.72) versus a concerning increase of 7.86% (± 5.67) in the placebo group (p=0.006). This p-value of 0.006 highlights the statistical significance of the drug’s impact on ECV.

• Echocardiographic parameters, including left atrial strain (LAS) and right ventricular free wall strain (RVFWS), were also assessed across the broader HELIOS-B population.
  • The LAS analysis correlated LAS measurements with baseline disease severity, mortality, and cardiovascular events. Patients on vutrisiran showed less worsening in LAS at 30 months relative to the placebo group, suggesting a protective effect on left atrial function.

  • Similarly, RVFWS analysis showed a stabilization of RVFWS among vutrisiran-treated patients at 30 months, compared to placebo. This suggests a stabilization of right ventricular function with the drug. Worsening RVFWS was strongly associated with a heightened risk of adverse outcomes.

Dr. Marianna Fontana, a HELIOS-B investigator at University College London, emphasized the clinical implications of these findings. “As ATTR-CM progressively damages the heart muscle, leading to worsening patient outcomes, the HELIOS-B CMR analysis offers encouraging initial evidence that vutrisiran can counteract these changes in some patients.” She added that the favorable impacts on cardiac structure, function, and the regression of amyloid burden suggest the drug’s potential not only to slow disease progression but also to potentially reverse structural damage due to amyloid deposition in some instances.

Renal Function and Cardiovascular Benefits in CKD Patients

Kidney involvement is a concerning comorbidity in ATTR-CM, often associated with disease progression and poor patient outcomes. Amyloid deposits in the kidneys cause a decline in kidney function, detectable by a decreasing estimated glomerular filtration rate (eGFR).

• A separate post-hoc analysis of the HELIOS-B data specifically evaluated vutrisiran’s effect on renal function. The efficacy and safety of vutrisiran were assessed in patients who progressed to severe chronic kidney disease (CKD) during the trial.

• The overall treatment group experienced fewer instances of ≥40% decreases in eGFR from baseline during the double-blind period, compared to placebo (12.7% vs 21.2%). This suggests that vutrisiran may offer a degree of renal protection.

• Patients who progressed to CKD Stage 4 or greater during the double-blind period showed a reduced risk of all-cause mortality (ACM) and cardiovascular events (hazard ratio [HR] 0.47; 95% confidence interval [CI]: 0.26–0.85), compared to those on placebo.

• These findings were consistent across the overall population and across various treatment subgroups, bolstering the consistency of vutrisiran’s benefits.

• Importantly, the safety profile of vutrisiran in patients with advanced CKD was consistent with the overall HELIOS-B study population, suggesting a tolerable risk-benefit profile, even in this vulnerable group.

“The new HELIOS-B analyses add depth to the growing body of evidence supporting AMVUTTRA’s first-line potential in ATTR-CM treatment,” noted Dr. John Vest, Senior Vice President at Alnylam. He emphasized that the benefits observed across various measures underscore the potential for the drug to protect multiple organs affected by this systemic disease.

The HELIOS-B findings have underpinned regulatory approvals of AMVUTTRA for ATTR-CM in numerous countries, including the United States, Brazil, the EU, and Japan. AMVUTTRA, administered via subcutaneous injection four times a year, leverages RNAi to rapidly reduce transthyretin production at its source. It has accumulated over 8,000 patient-years of experience globally and is the first RNAi therapeutic approved for both ATTR-CM and hATTR-PN. The new data presented at AHA further strengthens the case for broader adoption of AMVUTTRA in treating this devastating illness. Alnylam’s stock (ALNY) will likely react positively to these study results.

For pharmaceutical investors, Alnylam’s ongoing research and market expansion of AMVUTTRA are essential benchmarks to monitor. The drug’s potential to not only slow but potentially reverse certain aspects of ATTR-CM positions it as a crucial player in the future of amyloidosis treatment. This warrants a closer look at Alnylam’s strategic direction and its ability to capitalize on the drug’s expanding therapeutic profile.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) is at the forefront of RNA interference (RNAi) therapeutics. Their commercial products include AMVUTTRA (vutrisiran), ONPATTRO (patisiran), GIVLAARI (givosiran), and OXLUMO (lumasiran), with partners developing Leqvio (inclisiran) and Qfitlia (fitusiran).

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