CAMBRIDGE, Mass.-Alnylam Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) approval of its supplemental New Drug Application (sNDA) for AMVUTTRA® (vutrisiran), an RNA interference (RNAi) therapeutic for the treatment of transthyretin-mediated amyloidosis (ATTR) cardiomyopathy (ATTR-CM) in adults. This approval marks AMVUTTRA as the first and only FDA-approved therapy to reduce cardiovascular mortality, hospitalizations, and urgent heart failure visits in adults with ATTR-CM.
The new indication for AMVUTTRA expands its role in treating patients with both the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) and the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN). With this approval, AMVUTTRA solidifies its position as a groundbreaking, clinically differentiated treatment for patients with these life-threatening conditions.
ATTR-CM is a devastating, progressive, and often fatal disease that is estimated to affect approximately 150,000 people in the United States and over 300,000 people globally. This condition occurs when misfolded transthyretin (TTR) proteins accumulate as amyloid deposits in the heart, leading to irreversible damage and eventual heart failure. Despite its severity, ATTR-CM remains largely underdiagnosed, and many patients experience rapid disease progression even with current treatments. There are currently no curative therapies for this condition.
“This FDA approval of AMVUTTRA for ATTR-CM represents a major milestone for patients suffering from this debilitating disease,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam Pharmaceuticals. “We are proud to bring a new, innovative treatment option to patients and extend our sincere gratitude to the patients who participated in clinical trials, their families, caregivers, clinical researchers, and regulators who helped make this approval possible. This achievement reflects our nearly two-decade-long commitment to the ATTR amyloidosis community, and we remain dedicated to further advancing therapies to improve patients’ lives.”
AMVUTTRA is an RNAi therapeutic that works by silencing the production of TTR, the root cause of ATTR-CM. By reducing TTR levels through subcutaneous injections just four times a year, AMVUTTRA prevents the accumulation of amyloid fibrils that damage vital organs, particularly the heart. This mechanism of action distinguishes AMVUTTRA from existing therapies and offers a promising new approach to treating ATTR-CM.
“HELIOS-B, the Phase 3 clinical trial, demonstrated that vutrisiran not only reduced cardiovascular events and hospitalizations, but also significantly extended survival,” said Dr. Ronald Witteles, M.D., HELIOS-B Investigator, Professor of Medicine at Stanford University, and Co-Director of the Stanford Amyloid Center. “The trial enrolled a patient population that mirrors real-world ATTR-CM cases, and the results are very promising. Vutrisiran offers the potential for significant improvements in both cardiovascular outcomes and overall disease progression, making it an exciting option for patients with this challenging disease.”
The FDA approval is based on the compelling results from the HELIOS-B Phase 3 trial, which met all pre-specified primary and secondary endpoints. The study demonstrated that AMVUTTRA reduced the risk of all-cause mortality (ACM) and recurrent cardiovascular (CV) events by 28% compared to placebo over a treatment period of up to 36 months. A secondary analysis showed a 36% reduction in mortality through 42 months, which included both the double-blind treatment phase and six months of open-label extension. Furthermore, patients treated with AMVUTTRA showed preserved functional capacity and improved quality of life, as well as favorable early changes in biomarkers NT-proBNP and troponin I, which are predictive of cardiovascular outcomes.
The safety profile of AMVUTTRA has been well-established in previous clinical studies, including the HELIOS-A trial, which led to the FDA’s approval of AMVUTTRA for the treatment of hATTR-PN in 2022. In the HELIOS-B study for ATTR-CM, AMVUTTRA was generally well-tolerated, with the most common adverse reactions being pain in extremities (15%), arthralgia (11%), dyspnea (7%), and decreased vitamin A levels (7%). No new safety concerns were identified in this trial.
Muriel Finkel, President of the Amyloidosis Support Groups, emphasized the significance of this approval: “The approval of AMVUTTRA is a game-changer for the ATTR amyloidosis community. For families affected by this condition, the availability of a new, effective treatment brings hope and represents a critical step forward in managing this devastating disease.”
AMVUTTRA has already been covered by insurers for approximately 99% of patients with hATTR-PN, with many patients paying $0 out-of-pocket. Given the demonstrated clinical benefits in the HELIOS-B trial, similar broad coverage and low out-of-pocket costs are expected for ATTR-CM. Alnylam has established a strong track record in ensuring patient access through innovative value-based agreements with payers and has committed to continuing this work for the ATTR-CM community.
Through its comprehensive patient support program, Alnylam Assist®, the company offers resources to help patients and healthcare providers navigate the treatment process. This includes a Quick Start program to assist patients who experience delays in coverage, as well as support with insurance, financial assistance, and disease education. Physicians and patients can access these services by visiting AlnylamAssist.com/amvuttra or calling 1-833-256-2748.
Alnylam is also pursuing marketing authorization applications for AMVUTTRA in ATTR-CM with several global health authorities, including the European Medicines Agency (EMA), the Brazilian Health Regulatory Agency (ANVISA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), with additional regulatory submissions expected in 2025.
This approval further reinforces Alnylam’s leadership in the treatment of ATTR amyloidosis and its ongoing commitment to improving the lives of patients affected by this severe and under-recognized disease.
