European Commission Approves Alnylam's AMVUTTRA for ATTR Amyloidosis with Cardiomyopathy

Alnylam Pharmaceuticals, a leading company in RNA interference therapeutics, has announced that the European Commission has approved AMVUTTRA® (vutrisiran) for treating wild-type or hereditary transthyretin amyloidosis in adults with cardiomyopathy (ATTR-CM). This approval marks AMVUTTRA as the first RNA interference therapeutic approved by the EC for both cardiomyopathy and polyneuropathy manifestations of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, addressing a significant patient need in Europe.

Pushkal Garg, M.D., Chief Medical Officer at Alnylam, emphasized the importance of this approval in combating ATTR amyloidosis, a condition affecting approximately 100,000 people in Europe, most of whom suffer from cardiomyopathy. He highlighted the therapeutic's established efficacy and safety, demonstrated by over 6,000 patient-years of global experience in hATTR treatment. AMVUTTRA provides rapid and sustained TTR knockdown with quarterly dosing, offering a promising approach to transform patient outcomes for this serious condition.

The European Commission's decision was informed by the HELIOS-B Phase 3 study, a global, randomized, double-blind, placebo-controlled trial. This study involved a diverse patient population undergoing concurrent standard therapies like tafamidis and SGLT2 inhibitors. AMVUTTRA successfully met all ten pre-specified primary and secondary endpoints, including significant reductions in all-cause mortality and recurring cardiovascular events, improvements in functional capacity, health status, quality of life, and heart failure symptoms. In the overall population, AMVUTTRA achieved a 28% reduction in the composite endpoint of all-cause mortality and recurrent cardiovascular events compared to placebo, with a notable 36% reduction in mortality through 42 months.

The safety profile of AMVUTTRA was comparable to placebo, with similar incidences of adverse events, serious adverse events, and drug discontinuations. Notable side effects include reactions at the injection site and elevations in blood alkaline phosphatase and alanine transaminase levels. Detailed findings from HELIOS-B were published in The New England Journal of Medicine.

Marianna Fontana, M.D., Ph.D., a HELIOS-B investigator, praised the study's results, calling vutrisiran a potential first-line treatment for ATTR-CM patients. She emphasized the significance of enrolling a patient population reflective of real-world clinical practice, offering meaningful insights for clinical application. The introduction of AMVUTTRA marks a significant milestone in providing a new treatment option that could improve disease outcomes.

ATTR-CM is characterized by the deposition of misfolded TTR fibrils, causing irreversible cardiovascular damage and premature mortality. AMVUTTRA, an RNAi therapeutic, tackles the disease at its source by achieving sustained knockdown of TTR. Administered as a subcutaneous injection every three months, it offers flexible treatment delivery either by healthcare professionals or through self-administration by patients or their caregivers.

Giovanni d’Alessio, President of the Amyloidosis Alliance, expressed enthusiasm for the approval, noting its importance for the amyloidosis community. He highlighted the impact of amyloidosis on patients' physical health, quality of life, and independence, and welcomed the new treatment option for those in the EU.

Following the European Medicines Agency’s Committee for Orphan Medicinal Products' positive opinion on AMVUTTRA's orphan designation in May 2025, the therapeutic was previously approved by the U.S. FDA and Brazil's ANVISA in March 2025 for treating ATTR amyloidosis cardiomyopathy in adults. Alnylam is actively pursuing further global submissions to make vutrisiran accessible to more patients worldwide.