RX Review: Understanding ATTR-CM's New Era of Management - Episode null
RX Review: Impact of New, Upcoming Therapies for ATTR-CM
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In this video, part 3 of a 4-part series, panelists discuss the impact of recent approvals and pipeline developments on the outlook for ATTR-CM management.
After more than half a decade with tafamidis (Vyndamax) as the only FDA-approved therapy for transthyretin amyloid cardiomyopathy (ATTR-CM), the December 2024 and March 2025 approvals of disease-modifying therapies in acoramidis (Attruby) and vutrisiran (Amvuttra) have left clinicians better equipped than ever to meet the needs of this growing patient population.
In part 3 of our 4-part RX Review on updates and unmet needs in ATTR-CM, Mazen Hanna, MD, director of the Heart Failure Intensive Care Unit and codirector of the Amyloid Program at Cleveland Clinic, leads a discussion with Marian Vandyck-Acquah, MD, director of Education and Quality-Noninvasive Cardiology at Hackensack Meridian Health Heart and Vascular Hospital, and Jesus Almendral, MD, director of the Advanced Heart Failure Center at the Jersey Shore University Medical Center, on how recent FDA approvals for ATTR-CM therapies have influenced clinical decision-making.
Vandyck-Acquah outlines the evolving treatment landscape since 2018, highlighting a growing arsenal of therapeutic options. Initial treatments, such as tafamidis, provided the first disease-modifying approach, but subsequent trials, including ATTR-ACT, ATTRibute-CM, and ongoing gene-editing studies, have expanded possibilities. She notes that vutrisiran, originally approved for hereditary polyneuropathy, has now received FDA approval for cardiomyopathy, offering an alternative to stabilizers. However, she raises key questions: Which therapy should be used for which patient? When should combination therapy be considered? And how do these new agents fit into clinical practice?
Beyond approved therapies, the panel discuses gene-editing and fibril-removal strategies, which remain in experimental phases. Hanna emphasizes the lack of head-to-head data comparing tafamidis and acoramidis, making direct comparisons challenging. Differences in study populations—ATTRibute-CM included less severely ill patients than ATTR-ACT—further complicate cross-trial comparisons.
The discussion shifts to the question of combination therapy. Almendral notes that no current data definitively support its use. While the ATTRibute-CM study allowed tafamidis use in some patients receiving vutrisiran, no significant differences emerged between monotherapy and combination therapy groups. He acknowledges that, mechanistically, combining stabilizers and silencers may seem logical, but without direct evidence, routine combination therapy cannot be recommended.
Hanna concurs, referencing the HELIOS-B trial, where combination therapy showed only a nonsignificant trend toward mortality benefit. Given the high cost of these therapies, financial toxicity remains a critical concern. Until more data emerge, Hanna suggests most clinicians are likely to reserve combination therapy for cases of disease progression rather than as an initial strategy.
Our Panelists:
Mazen Hanna, MD, is a cardiologist at the Cleveland Clinic's Vascular & Thoracic Institute. Hanna is also director of the Heart Failure Intensive Care Unit and codirector of the Amyloid Program at Cleveland Clinic and serves as the moderator for this panel discussion.
Marian Vandyck-Acquah, MD, is an assistant professor of medicine in the cardiology department at the Hackensack Meridian School of Medicine. Vandyck-Acquah is also the director of Education and Quality-Noninvasive Cardiology at Hackensack Meridian Health Heart and Vascular Hospital.
Jesus Almendral, MD, is a cardiovascular disease specialist board-certified in advanced heart failure and heart transplant, cardiovascular disease and internal medicine at the Jersey Shore University Medical Center. He is the director of the Advanced Heart Failure Center at the center and serves as the third panelist for our discussion.
Relevant disclosures for Hanna include Pfizer, Alnylam, Ionis, and Eidos. Almendral and Vandyck-Acquah have no relevant disclosures to report.
References:
Office of the Commissioner. FDA approves new treatments for heart disease caused by a serious rare disease, transthyretin mediated amyloidosis. FDA. Published May 6, 2019. Accessed March 28, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatments-heart-disease-caused-serious-rare-disease-transthyretin-mediated.
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 22, 2024. Accessed March 28, 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/.
Alnylam. Alnylam Announces FDA Approval of AMVUTTRA® (vutrisiran), the First RNAi Therapeutic to Reduce Cardiovascular. Investor Relations | Alnylam Pharmaceuticals, Inc. Published March 20, 2025. Accessed March 28, 2025. https://investors.alnylam.com/press-release?id=28831.
