Alnylam Pharmaceuticals, Inc. announced results from new 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 a post hoc analysis of the HELIOS-B study, which assessed whether treatment with vutrisiran was associated with a reduction in gastrointestinal (GI) adverse events in patients with ATTR-CM, compared to placebo, were presented during a late-breaking session at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025 in Minneapolis, Minnesota. The analysis showed that treatment with vutrisiran was associated with a lower rate of GI events across the overall, vutrisiran monotherapy, and baseline tafamidis treatment groups, compared to placebo, a trend that was consistent in patients living with both the wild-type and hereditary forms of the disease.
Patients with ATTR-CM often experience disease manifestations beyond the heart including GI events such as diarrhea, abdominal pain and discomfort, constipation, nausea, and vomiting. In the analysis, a 42% lower rate of GI events was observed in patients treated with vutrisiran in the overall population, compared to placebo. Consistent results were also observed across the vutrisiran monotherapy group and in patients treated with tafamidis at baseline.
In the vutrisiran monotherapy group, a 37% lower rate of GI events was observed, compared to placebo. In the baseline tafamidis group, a 49% lower rate of GI events was observed, compared to placebo. When looking specifically at individual GI symptoms known to significantly impact quality of life (QOL), including diarrhea, nausea, and vomiting, reductions of greater than 50% were observed across all three study populations: the overall population, the vutrisiran monotherapy population, and the population of patients treated with tafamidis at baseline.
This corresponded to rate ratios (RR) for diarrhea of 0.46, 0.48, and 0.44; for nausea of 0.35, 0.17, and 0.48; and for vomiting of 0.16, 0.25, and 0.00, respectively. The lower rate of GI events in patients treated with vutrisiran, compared to placebo, was observed as early as three months and was consistent across hereditary and wild-type patients throughout the double-blind period. These findings suggest a potential treatment effect in all study populations assessed.
A second post hoc analysis of the HELIOS-B study presented at the HFSA Annual Scientific Meeting assessed the efficacy and safety of vutrisiran as a monotherapy by censoring patients who initiated tafamidis during the double-blind period at investigator discretion. This analysis was designed to isolate the effect of vutrisiran treatment alone, without the potential confounding influence of additional therapy. Tafamidis initiation occurred in 21.5% of monotherapy patients, with a median time to initiation of approximately 12 months.
In this censored monotherapy population, patients treated with vutrisiran demonstrated a statistically significant 32% reduction in the risk of the primary composite endpoint of all-cause mortality and recurrent cardiovascular events through 36 months, compared to patients who received placebo (hazard ratio [HR] 0.68; 95% confidence interval [CI]: 0.49?0.95; p=0.022). These results were consistent with the primary monotherapy analysis of the study which included patients who later initiated tafamidis (HR 0.67; 95% CI: 0.49?0.93; p=0.016). Moreover, within the censored population, outcomes for the secondary endpoints and safety findings were consistent with the results of the primary analysis.
These results reinforce the findings from the powered monotherapy subgroup and provide further evidence of vutrisiran?s efficacy and safety as a standalone first-line therapy, without the confounding effects of additional treatments. A third post hoc analysis of the HELIOS-B study evaluated outcomes by baseline Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score, and demonstrated that treatment with vutrisiran resulted in consistent benefits in survival, cardiovascular outcomes, functional capacity, quality of life, cardiac biomarkers, and reduced GI adverse events, regardless of baseline health status. Data from the HELIOS-B study supported the recent approvals of AMVUTTRA for the treatment of the cardiomyopathy of wild-type or hereditary ATTR-CM in adults in the United States (US), Brazil, European Union (EU), Japan, United Arab Emirates (UAE) and United Kingdom (UK).
Collectively, AMVUTTRA has more than 8,000 patient-years of experience worldwide and is the first RNAi therapeutic approved for the treatment of both the cardiomyopathy manifestations of ATTR amyloidosis and the polyneuropathy manifestations of hereditary transthyretin-mediated amyloidosis (hATTR) in adults.
