Vutrisiran (Amvuttra) reduces the risk of cardiovascular death, hospital admissions, and urgent heart failure visits in adults with transthyretin-mediated amyloidosis with cardiomyopathy, according to results from a phase III trial. 

The FDA has approved an expanded indication for vutrisiran, an RNA interference (RNAi) therapeutic developed by Alnylam Pharmaceuticals, for the treatment of cardiomyopathy associated with wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults. The approval allows use of vutrisiran to reduce cardiovascular mortality, hospitalizations, and urgent heart failure visits. It is now the first therapy approved in the U.S. for both cardiomyopathy and polyneuropathy manifestations of ATTR amyloidosis. 

ATTR-CM is a progressive and often fatal disease linked to misfolded transthyretin protein. Vutrisiran reduces transthyretin production at the RNA level, thereby addressing the underlying pathophysiology. The treatment is administered subcutaneously every 3 months.

The phase III HELIOS-B trial evaluated vutrisiran for the treatment of ATTR-CM; investigators determined the therapy achieved statistical significance compared to placebo. The trial met all 10 prespecified primary and secondary endpoints. During the double-blind period (up to 36 months), receipt of vutrisiran was associated with a 28% relative reduction in the composite of all-cause mortality and recurrent cardiovascular events. In a secondary analysis through 42 months, which included an open-label extension, a 36% reduction in mortality was reported. Among patients who received vutrisiran as monotherapy, the reduction in cardiovascular events and mortality reached 33% and 35%, respectively.

Patients receiving vutrisiran demonstrated preservation of functional capacity and quality of life, as well as early improvements in biomarkers associated with cardiac stress, including NT-proBNP and troponin I. No new safety concerns were identified in the HELIOS-B trial. Common adverse events previously reported in the hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) population included extremity pain, arthralgia, dyspnea, and decreased vitamin A levels.

Alnylam reported that insurance coverage for vutrisiran in hATTR-PN exceeds 99%, with most patients paying no out-of-pocket costs, and the company expects similar coverage for ATTR-CM. Regulatory review of vutrisiran for ATTR-CM is ongoing in several international markets.

Reference:

Alnylam Pharmaceuticals. 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). Published March 20, 2025. Accessed March 21, 2025. https://investors.alnylam.com/press-release?id=28831