Navigating Treatment in ATTR-CM's New Era, with Ahmad Masri, MD, MS

The approvals of acoramidis (Attruby) and vutrisiran (Amvuttra) represent a step forward into a new era of management for transthyretin-mediated amyloidosis cardiomyopathy (ATTR-CM). Awarded in November 2024 and March 2025, respectively, the agents represent the latest in a new wave of therapeutic advancement, which now gives cardiologists multiple options boasting unique mechanisms of action.

“Everybody used to be offered tafamidis as a first-line therapy for patients with transact income. Now this has changed since the approval of acoramidis and the recent approval of vutrisiran. This has changed—now, you're going to sit with the patient, you're going to think about the options,” said Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University, in an interview with HCPLive at American College of Cardiology (ACC) 2025 Annual Scientific Sessions.

Acoramidis is an orally-administered near-complete stabilizer of transthyretin (TTR). Upon approval in November, the agent became the first approved product with a label specifying near-complete stabilization of TTR. The agent was approved based on data from the ATTRibute-CM study, which concluded use of acoramidis was associated with a statistically significant reduction in the primary endpoint of all-cause mortality and cumulative frequency of cardiovascular-related hospitalizations at 30 months.

Vutrisiran is a subcutaneous siRNA therapeutic that inhibits the production of TTR protein and was initially approved by the FDA for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis. The label expansion to include or the treatment of the cardiomyopathy of wild-type or hereditary ATTR-CM in adults to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits was based on the HELIOS-B trial, which concluded use was associated with a statistically significant benefit on all 10 prespecified primary and secondary endpoints.

Relevant disclosures for Masri include Cytokinetics, Bristol Myers Squibb, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, BioMarin, and AstraZeneca.

References:

1. BridgeBio. AttrubyTM (acoramidis), a Near Complete TTR Stabilizer (≥90%), approved by FDA to Reduce Cardiovascular Death and Cardiovascular-related Hospitalization in ATTR-CM Patients - BridgeBio. BridgeBio. Published November 23, 2024. Accessed April 1, 2025. https://bridgebio.com/news/attruby-acoramidis-a-near-complete-ttr-stabilizer-%E2%89%A590-approved-by-fda-to-reduce-cardiovascular-death-and-cardiovascular-related-hospitalization-in-attr-cm-patients/.

2. Alnylam Pharmaceuticals. Alnylam Announces FDA Approval of AMVUTTRA® (vutrisiran), the First RNAi Therapeutic to Reduce Cardiovascular. Investor Relations | Alnylam Pharmaceuticals, Inc. Published March 20, 2025. Accessed April 1, 2025. https://investors.alnylam.com/press-release?id=28831.