FDA Approves Alnylam’s AMVUTTRA® for ATTR-CM Treatment
Alnylam Pharmaceuticals, Inc., a pioneer in RNAi therapeutics, has announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for its RNAi-based therapeutic, AMVUTTRA® (vutrisiran). This approval extends the indication of AMVUTTRA for the treatment of the cardiomyopathy associated with wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults, with the goal of reducing cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits. With this expanded indication, AMVUTTRA is now the first and only FDA-approved therapy for both ATTR-CM and the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.
ATTR-CM is a progressive and life-threatening disorder that affects an estimated 150,000 individuals in the United States and over 300,000 worldwide. Characterized by the deposition of misfolded transthyretin (TTR) fibrils in the heart, the disease leads to irreversible damage, heart failure, and premature death. Despite the availability of treatments, many patients remain undiagnosed or untreated, while others experience disease progression despite therapy.
“The FDA approval of AMVUTTRA for ATTR-CM is a landmark achievement that provides a new, clinically differentiated option to improve patient outcomes, including cardiovascular mortality reduction and disease progression mitigation,” stated Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. “This milestone reflects our unwavering commitment to advancing RNAi therapeutics and our nearly two-decade-long partnership with the ATTR amyloidosis community. We extend our deepest appreciation to the patients, caregivers, researchers, and regulators who made this breakthrough possible. We remain dedicated to innovation in ATTR amyloidosis to help patients live longer, healthier lives.”
AMVUTTRA operates by targeting TTR production at its source through RNA interference (RNAi). This mechanism allows for a significant reduction in TTR protein levels, decreasing the accumulation of TTR fibrils that cause ATTR-CM. The treatment is administered as a subcutaneous injection once every three months, offering patients a convenient and effective therapeutic option.
Dr. Ronald Witteles, a principal investigator in the HELIOS-B clinical trial and Co-Director of the Stanford Amyloid Center, emphasized the importance of this approval: “This marks a crucial step in the evolution of ATTR-CM treatment. The HELIOS-B trial demonstrated that vutrisiran not only extended patient survival but also significantly reduced hospitalizations and improved overall patient function. The trial was conducted in a diverse patient population reflective of real-world conditions, reinforcing the broad applicability of AMVUTTRA in clinical practice. The observed benefits across cardiovascular outcomes and multiple disease progression markers make this an exciting development for patients with ATTR-CM.”
The FDA’s approval of AMVUTTRA is supported by data from the Phase 3 HELIOS-B study, which assessed its efficacy and safety in treating ATTR-CM. The study demonstrated statistically significant improvements across all ten pre-specified primary and secondary endpoints compared to placebo. Notably, AMVUTTRA reduced the risk of all-cause mortality (ACM) and recurrent cardiovascular (CV) events by 28% during the 36-month double-blind treatment period. Further analysis indicated a 36% reduction in mortality over 42 months when including six months of open-label extension data. Additionally, among patients receiving AMVUTTRA as monotherapy, the risk of ACM and recurrent CV events decreased by 33% in the double-blind period, while mortality risk was reduced by 35% over 42 months.
Beyond survival benefits, AMVUTTRA-treated patients exhibited superior preservation of functional capacity and quality of life. Early reductions in NT-proBNP and troponin I—key biomarkers predictive of cardiovascular outcomes—further supported its clinical efficacy. The safety profile of AMVUTTRA remains consistent with findings from the HELIOS-A trial in hATTR-PN, with over 5,000 patient-years of exposure globally. Reported adverse reactions include pain in extremities (15%), arthralgia (11%), dyspnea (7%), and decreased vitamin A levels (7%). No new safety concerns emerged in the HELIOS-B trial.
Muriel Finkel, President of the Amyloidosis Support Groups, highlighted the significance of this approval: “Even with recent treatment advances, ATTR-CM remains a devastating disease that profoundly affects patients and families. I have witnessed firsthand the hardships faced by those living with ATTR amyloidosis, including diminished quality of life and loss of loved ones. The approval of AMVUTTRA is a monumental step forward, providing new hope to our community.”
Access to AMVUTTRA is expected to be widespread, with insurance coverage anticipated to be similar to that of its use in hATTR-PN, where approximately 99% of patients face minimal or no out-of-pocket costs. Alnylam has a history of working closely with payers to establish innovative, value-based agreements linked to clinical outcomes, ensuring affordability and access for patients. The company remains committed to maintaining broad reimbursement for AMVUTTRA and supporting patients through its Alnylam Assist® program.
Alnylam Assist® offers comprehensive patient support services, including personalized guidance on insurance coverage, financial assistance, and treatment education. Additionally, the program provides a Quick Start initiative that supplies eligible patients with an initial dose at no cost if they encounter insurance or treatment delays. Physicians and patients can learn more about Alnylam Assist® by visiting AlnylamAssist.com/amvuttra or calling 1-833-256-2748.
Beyond the United States, regulatory applications based on HELIOS-B data are under review by several health agencies, including the European Medicines Agency (EMA), Brazil’s National Health Surveillance Agency (ANVISA), and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). Alnylam remains on track to submit additional global regulatory applications for vutrisiran in 2025, aiming to expand patient access to this groundbreaking therapy worldwide.
The approval of AMVUTTRA for ATTR-CM underscores Alnylam’s leadership in RNAi therapeutics and its dedication to transforming the treatment landscape for patients with ATTR amyloidosis. By addressing the disease at its molecular origin, AMVUTTRA offers a clinically meaningful and highly differentiated therapeutic option for individuals suffering from this devastating condition. As Alnylam continues to innovate, it remains steadfast in its mission to improve patient lives through the power of RNAi technology.
