(T1130-05-32) Acoramidis Improved Clinical Outcomes, Function, Quality of Life and NT-proBNP in Patients with Transthyretin Amyloid Cardiomyopathy Regardless of Atrial Fibrillation Status at Baseline

Purpose: Atrial fibrillation (AF) significantly impacts quality of life (QoL) and is often observed in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Acoramidis achieves near-complete (≥90%) transthyretin (TTR) stabilization,¹ and is approved in the USA, Europe, Japan, and the UK for the treatment of ATTR-CM in adults. In the phase 3 ATTRibute-CM study (NCT03860935), acoramidis treatment significantly reduced the time to all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) at Month 30, and resulted in improved 6-minute walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels relative to placebo.^2,3 The clinical efficacy of acoramidis has not yet been reported in patients with ATTR-CM and with an AF or atrial flutter (AFL) diagnosis at baseline. The purpose of this study was to assess the effects of acoramidis treatment on ACM or first CVH, 6MWD, KCCQ-OS scores, and NT-proBNP levels at Month 30 in participants with ATTR-CM with or without AF/AFL diagnosis at baseline.

Methods: The ATTRibute-CM study design has been previously published.³ This post hoc analysis included participants in the modified intention-to-treat population (N=611) grouped by AF/AFL diagnosis at baseline (defined as recorded AF medical history or the presence of AF or AFL on an ECG at enrollment). The rate of ACM or first CVH at Month 30 was compared between groups using a stratified Cox proportional hazards model. Changes from baseline to Month 30 in 6MWD, KCCQ-OS scores and NT-proBNP levels were summarized descriptively.

Results: Overall, 62.8% (384/611) of participants had an AF/AFL diagnosis at baseline (acoramidis: 255/409, placebo: 129/202). These participants had lower mean 6MWD and KCCQ-OS scores and higher median NT-proBNP levels than those without AF/AFL diagnosis at baseline. Treatment with acoramidis reduced ACM or first CVH, slowed the decline in 6MWD and KCCQ-OS scores and blunted the rise in NT-proBNP compared with placebo, regardless of AF/AFL diagnosis at baseline (Table).

Conclusion: Acoramidis improved clinical outcomes (ACM, CVH), functional status, QoL and NT-proBNP levels relative to placebo in participants with ATTR-CM, regardless of AF/AFL diagnosis at baseline.

References: 1. Judge DP, et al. J Am Coll Cardiol. 2019;74(3):285-295.
2. Judge DP, et al. J Am Coll Cardiol. 2025;85(10):1003-1014.
3. Gillmore JD, et al. N Engl J Med. 2024;390;132-142.

Acknowledgements:

Funding: This study was sponsored by BridgeBio Pharma, Inc., San Francisco, CA, USA. Acknowledgements: Under the direction of the authors, medical writing assistance was provided by Oxford PharmaGenesis, Inc., and was funded by BridgeBio Pharma, Inc. We thank Jean-François Tamby, Adam Castaño and Jonathan C. Fox as authors from the original author group. Conflicts of interest: B.W.S. has acted as a speaker for Pfizer and a consultant for Alnylam, AstraZeneca and BridgeBio Pharma, Inc A.M. has acted as a researcher for Attralus, Cytokinetics, Ionis Pharmaceuticals, and Pfizer; and as a consultant, advisor, or speaker for Akros Pharma, Alexion Pharmaceuticals, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BioMarin Pharmaceutical, BridgeBio Pharma, Inc., Bristol Myers Squibb, Cytokinetics, Haya Therapeutics, Ionis Pharmaceuticals, Lexicon Pharmaceuticals, Pfizer, Prothena Biosciences, and Tenaya Therapeutics. M.G. has acted as a researcher for Alnylam Pharmaceuticals, BridgeBio Pharma, Inc., Intellia Therapeutics, Janssen Pharmaceuticals, Novo Nordisk, and Pfizer; and as a consultant, advisor, or speaker for Alnylam, BridgeBio Pharma, Janssen Pharmaceuticals, Novo Nordisk, and Pfizer. D.M. and O.A. have acted as consultants, advisors, or speakers for Pfizer. B.D. has acted as a consultant for Alnylam Pharmaceuticals and Eidos. J.N-N. has acted as a researcher for Alnylam Pharmaceuticals, AstraZeneca, BridgeBio Pharma (formerly Eidos Therapeutics), and Pfizer. M.K. has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli-Lilly, Mochida pharmaceutical company, Nova Biomedical, and Novartis. C.C. and D.W. are employees and stakeholders of BridgeBio Pharma, Inc. R.C. has no relevant financial relationships to disclose. D.P.J. has received consultancy fees from Alexion Pharmaceuticals, Alleviant Medical, Alnylam Pharmaceuticals, Attralus, BridgeBio Pharma, Inc., Cytokinetics, Lexeo Therapeutics, Novo Nordisk, Pfizer, Renovacor, Rocket Pharmaceuticals, and Tenaya Therapeutics; and his institution received clinical trial funding from Array Biopharma, BridgeBio Pharma, Inc., MyoKardia, and Pfizer. F.C. has acted as a consultant, advisor, or speaker for Alnylam Pharmaceuticals, Amicus Therapeutics, AstraZeneca, Bayer, BridgeBio Pharma, Inc., Novo Nordisk, and Pfizer.

Table 1. Clinical efficacy of acoramidis at Month 30 by AF/AFL diagnosis at baselinea; mITT population (N=611).