On March 20, 2025, the U.S. Food and Drug Administration (FDA) granted Alnylam Pharmaceuticals Inc. (Nasdaq: ALNY) a supplemental New Drug Application (sNDA) approval for AMVUTTRA® (vutrisiran) to treat transthyretin-mediated amyloidosis (ATTR). The FDA recently approved an expansion of AMVUTTRA therapy to treat cardiomyopathy in patients with both inherited and non-inherited ATTR (ATTR-CM) while also providing care for polyneuropathy due to inherited ATTR (hATTR-PN). This approval establishes AMVUTTRA as the first therapy authorized by the FDA to manage the total disease spectrum of ATTR-CM in adults.
ATTR-CM, a severe and progressive condition, affects approximately 150,000 U.S. patients along with more than 300,000 individuals worldwide. The heart condition produces premature death while causing permanent tissue destruction through the heart’s buildup of misfolded transthyretin (TTR) fibrils. Several patients with ATTR-CM continue to receive inadequate clinical care despite recent medical developments; hence, more effective treatment strategies are needed.
The gene-silencing process called RNA interference (RNAi), which is created through natural biological mechanisms, has transformed biology and drug development fields. RNAi received the 2006 Nobel Prize in Physiology or Medicine so scientists could develop RNAi therapeutics. The pharmaceutical compounds employ small interfering RNA (siRNA) molecules to stop the activity of messenger RNA (mRNA), which prevents the creation of disease-causing proteins. This revolutionary technique shows promise to transform genetic and disease treatment methods.
The RNAi technology in Alnylam’s AMVUTTRA onsets an immediate decrease in TTR protein levels to target the fundamental source of the disease. Subcutaneous administration of the therapy on a quarterly basis helps reduce amyloid accumulation while decreasing cardiovascular events and leading to better patient survival statistics.
After the HELIOS-B Phase 3 clinical trial demonstrated that AMVUTTRA decreased the risk of recurrent cardiovascular events and the all-cause mortality rate by 28% over a 36-month period, the FDA approved the medication. Research showed monotherapy patients experienced a hazard reduction of 33%, resulting in a 35% decrease in mortality throughout 42 months. In addition to reporting improved quality of life and notable reductions in cardiovascular risk biomarkers used to predict future events, patients also experienced increased functional capacity.
Dr. Ronald Witteles from Stanford University, as a HELIOS-B investigator, explained the clinical relevance of this treatment approval because it introduces a new mechanism of action that provides significant benefits to patient life expectancy alongside reduced hospitalization rates and improved patient health outcomes.
Alnylam established comprehensive patient support programs that ensure patients have access to treatment. Most patients taking AMVUTTRA will have their medication costs fully compensated by their health insurance or other programs. Through its Alnylam Assist® program, the company provides patients with financial assistance, insurance guidance, and education materials to ensure smooth patient access to treatment.
Regulatory agencies in Europe, Brazil, and Japan are currently reviewing AMVUTTRA for approval, signaling potential global expansion. Further regulatory applications for 2025 will expand the availability of therapy across different regions.
As the global leader of RNAi-based medicine, Alnylam has developed treatment technologies that silence genes for conditions that traditional medicines cannot reach. Multiple RNAi treatments developed by the company aim to treat both genetic and chronic conditions with significant unmet medical needs. This achievement serves to demonstrate how RNAi technology can revolutionize disease management along with Alnylam’s successful celebration of AMVUTTRA’s approval. The company continues to advance its efforts in treatment development while expanding availability for patients diagnosed with ATTR amyloidosis.
References: Alnylam announces FDA approval of AMVUTTRA® (vutrisiran), the first RNAi therapeutic to reduce cardiovascular death, hospitalizations, and urgent heart failure visits in adults with ATTR amyloidosis with cardiomyopathy (ATTR-CM). Alnylam Pharmaceuticals, Inc. March 20, 2025. https://investors.alnylam.com/press-release?id=28831
