− Treatment with Vutrisiran Led to 37- 49% Lower Rates of Gastrointestinal Events, a Multisystem Manifestation of ATTR-CM, Across Multiple Treatment Groups, Compared to Placebo –
− Additional Analyses Reinforce Vutrisiran’s Safety and Efficacy Profile as a Monotherapy and Illustrate Consistent Benefit from Treatment with Vutrisiran Across a Range of Patients’ Baseline Health Status and Quality of Life –
− Findings Presented at the Heart Failure Society of America Annual Scientific Meeting 2025 Highlight the Impact of Vutrisiran which Delivers Rapid Knockdown of Transthyretin –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today 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.
“As a multisystem disease, it is well-known that ATTR-CM impacts more than just the heart,” said Marcus Urey, M.D., Associate Professor, University of California San Diego Health. “For patients living with both hereditary and wild-type forms of the disease, gastrointestinal complications such as diarrhea, abdominal pain, constipation, nausea, and vomiting are a part of their journey with ATTR-CM, with some of these symptoms often significantly impacting their quality of life. As a physician who sees the multisystem impact of this disease every day, I am encouraged by these findings which underscore vutrisiran’s differentiated clinical profile and its potential to address the multisystem nature of this disease.”
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.
“The new HELIOS-B analyses presented at the HFSA Annual Scientific Meeting build on AMVUTTRA’s differentiated first-line profile,” said John Vest, M.D., Senior Vice President, TTR Global Clinical Lead, Alnylam. “We understand that gastrointestinal symptoms place a significant burden on patients, thus I’m encouraged to observe a reduction in these events in as early as three months after initiation of treatment. These findings, taken together with further evidence of AMVUTTRA’s strong monotherapy profile, underscore its potential to deliver meaningful impact as a first-line treatment for patients living with this rapidly progressive multisystem disease.”
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.
For additional information on Alnylam’s presentations at the HFSA Annual Scientific Meeting 2025, please visit Capella.
Indications and Important Safety Information
Indications Approved by the U.S. FDA
AMVUTTRA® (vutrisiran) is indicated for the treatment of the:
- cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits.
- polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.
Important Safety Information
Reduced Serum Vitamin A Levels and Recommended Supplementation
AMVUTTRA treatment leads to a decrease in serum vitamin A levels.
Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body.
Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).
Adverse Reactions
In a study of patients with hATTR-PN, the most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).
In a study of patients with ATTR-CM, no new safety issues were identified.
For additional information about AMVUTTRA, please see the full U.S. Prescribing Information (revised March 2025)
