CAMBRIDGE, Mass.– Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the RNAi therapeutics company, announced new analyses from the Phase 3 HELIOS-B study of AMVUTTRA® (vutrisiran) showing significant reductions in gastrointestinal (GI) adverse events among patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The findings were presented during a late-breaking session at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025 in Minneapolis.
In a post hoc analysis, patients treated with vutrisiran showed a 42 percent lower rate of GI events compared with placebo across the overall study population. In the vutrisiran monotherapy group, the reduction was 37 percent, while patients who had been treated with tafamidis at baseline saw a 49 percent reduction. The improvements were consistent across both wild-type and hereditary forms of the disease and were observed as early as three months. Reductions greater than 50 percent were seen in diarrhea, nausea, and vomiting across all treatment groups.
“As a multisystem disease, ATTR-CM impacts more than just the heart,” said Marcus Urey, M.D., associate professor at University of California San Diego Health. “For patients living with both hereditary and wild-type forms, gastrointestinal complications can significantly impact quality of life. These results underscore vutrisiran’s differentiated clinical profile and its potential to address the multisystem nature of this disease.”
A second analysis examined vutrisiran as a monotherapy, censoring patients who initiated tafamidis during the trial. In this group, vutrisiran treatment was associated with a 32 percent reduction in risk of all-cause mortality and recurrent cardiovascular events through 36 months compared with placebo (HR 0.68; 95% CI: 0.49–0.95; p=0.022). These findings were consistent with the primary analysis and reinforced the drug’s efficacy and safety as a standalone first-line therapy.
“The new HELIOS-B analyses presented at HFSA build on AMVUTTRA’s first-line profile,” said John Vest, M.D., senior vice president, TTR global clinical lead at Alnylam. “I’m encouraged to see reductions in gastrointestinal events as early as three months after treatment initiation. Taken together with the monotherapy results, these findings support AMVUTTRA’s role as a first-line treatment for this rapidly progressive multisystem disease.”
A third analysis of HELIOS-B data showed that vutrisiran provided consistent benefits across survival, cardiovascular outcomes, functional capacity, quality of life, cardiac biomarkers, and GI events regardless of patients’ baseline health status, as measured by Kansas City Cardiomyopathy Questionnaire scores.
Data from HELIOS-B supported recent global approvals of AMVUTTRA for cardiomyopathy caused by wild-type or hereditary ATTR-CM in adults. The therapy now has more than 8,000 patient-years of experience worldwide and is the first RNAi therapeutic approved for both cardiomyopathy and polyneuropathy manifestations of ATTR amyloidosis.
