Alnylam Pharmaceuticals, Inc., a global leader in RNAi therapeutics, has announced U.S. FDA approval of AMVUTTRA® (vutrisiran) for the treatment of cardiomyopathy associated with wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults. This approval makes AMVUTTRA the first and only U.S. FDA-approved therapeutic to address both cardiomyopathy and polyneuropathy (hATTR-PN) in ATTR amyloidosis.
ATTR-CM is a rare, progressive, and life-threatening disease that affects approximately 150,000 people in the U.S. and over 300,000 globally. It is caused by the accumulation of misfolded transthyretin (TTR) fibrils, leading to irreversible damage to the heart and reduced life expectancy. AMVUTTRA, an RNAi therapeutic, reduces TTR production at its source, effectively mitigating fibril deposition and disease progression.
“The FDA approval of AMVUTTRA for ATTR-CM marks a pivotal advancement for patients, providing a new and clinically differentiated treatment option that has been shown to improve outcomes, including cardiovascular mortality, and reduce progression for those living with this devastating disease,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam.
HELIOS-B Trial Results Drive Approval
The FDA approval is based on the Phase 3 HELIOS-B clinical trial, where AMVUTTRA achieved statistically significant results across all 10 pre-specified primary and secondary endpoints compared to placebo. The trial demonstrated a 28% reduction in all-cause mortality (ACM) and recurrent cardiovascular events over 36 months. Additionally, a 36% reduction in mortality was observed through 42 months in a secondary analysis, including the double-blind period and an open-label extension phase.
“This FDA approval provides an opportunity to further transform ATTR-CM treatment with a new mechanism of action. The HELIOS-B clinical trial found that vutrisiran allowed patients to live longer, experience fewer hospitalizations, and improve how they function and feel,” said Ronald Witteles, M.D., HELIOS-B Investigator and Professor of Medicine at Stanford University.
Patients treated with AMVUTTRA also experienced improvements in biomarkers such as NT-proBNP and troponin I, which are predictive of cardiovascular outcomes. Functional capacity and quality of life were also preserved among patients receiving AMVUTTRA. The therapy’s safety profile, consistent with previous trials, showed no new safety concerns in ATTR-CM patients.
Broad Patient Access and Support
Alnylam is committed to ensuring broad access to AMVUTTRA through its Alnylam Assist® program, which offers patients support with insurance, financial assistance, and educational resources. Most patients are expected to have $0 out-of-pocket costs for the therapy.
Despite recent advances, there remains a significant need for patients living with ATTR-CM and I’ve witnessed, firsthand, the impact that ATTR amyloidosis can have on families, including diminished quality of life and the loss of loved ones,” said Muriel Finkel, President of the Amyloidosis Support Groups. “The availability of this groundbreaking treatment option is a significant moment for patients living with ATTR amyloidosis. It represents a beacon of hope for our community.”
Global Reach and Future Plans
In addition to the U.S. approval, marketing authorization applications for AMVUTTRA are currently under review by global health agencies, including the European Medicines Agency (EMA), the Brazilian Health Regulatory Agency (ANVISA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Alnylam plans to submit additional regulatory applications worldwide throughout 2025.
