Treatment With Acoramidis Reduces Days Lost To Death And/or Cardiovascular-related Hospitalization, Preserving Time Alive Outside The Hospital In Patients With Transthyretin Amyloid Cardiomyopathy: Results From ATTRibute-CM

View session detail

Author Block: Richard Wright¹, Jose Nativi-Nicolau², Nitasha Sarswat³, Pooja Prasad⁴, Steen Hvitfeldt Poulsen⁵, Peter van der Meer⁶, Richard K. Cheng⁷, Martha Cao⁸, Jean-François Tamby⁹, Liana Hennum¹⁰, Heather Falvey¹¹, Julian D. Gillmore¹². ¹Pacific Heart Institute and Providence, Saint John's Health Center, Santa Monica, CA; ²Department of Transplant, Mayo Clinic, Jacksonville, FL; ³University of Chicago Medicine, Chicago, IL; ⁴Department of Cardiology, University of California San Francisco, San Francisco, CA; ⁵Department of Cardiology, Aarhus University Hospital, Aarhus, CA; ⁶University Medical Center Groningen, Groningen, Netherlands; ⁷University of Washington, Seattle, WA; ⁸BridgeBio Pharma, Inc., San Franciso, CA; ⁹BridgeBio Pharma, Inc., San Francisco, CA; ¹⁰BridgeBio Pharma, Inc, Minneapolis, MN; ¹¹BridgeBio Pharma, Inc, San Francisco, CA; ¹²National Amyloidosis Centre, University College London, London, United Kingdom
Disclosure Block: R. Wright: None. N. Sarswat: None. P. Prasad: None. R.K. Cheng: None. J.D. Gillmore: Advisory Panel; Pharmaceutical Company/Distributors; Alnylam Pharmaceuticals, Ionis Pharmaceuticals, Akcea Therapeutics, Intellia Therapeutics, Eidos Therapeutics, Pfizer, Lycia.

Introduction: In ATTRibute-CM, acoramidis, an approved, oral treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), reduced the risk of all-cause mortality or first cardiovascular-related hospitalization (CVH) through Month 30 by 36% vs placebo. Days lost to death and/or CVH (DLDCVH) is a patient-centered metric that integrates mortality, frequency of CVH, and length of hospital stay into a single measure of disease burden and healthcare resource utilization; reductions reflect fewer inpatient bed days and more time alive outside the hospital.
Hypothesis: Acoramidis reduces DLDCVH vs placebo in participants with ATTR-CM over 30 and 36 months.
Methods: ATTRibute-CM participants were randomized 2:1 to acoramidis HCl 800 mg or placebo twice daily for 30 months. This post hoc analysis assessed DLDCVH (using adjudicated CVH) vs placebo in the modified intention-to-treat population. The 30-month analysis used model-based estimates for participants with 907 days of follow-up, corresponding to the maximum follow-up duration (30 months) in ATTRibute-CM. For the 36-month analysis, estimates were generated for participants with 1080 days of follow-up using two analyses: the observed analysis used ATTRibute-CM data plus up to 6 months of open-label extension (OLE; in which all participants received open-label acoramidis) data for all participants; the modeled analysis used ATTRibute-CM data plus up to 6 months of OLE data for acoramidis participants, and only ATTRibute-CM data for placebo participants.
Results: Baseline demographics and characteristics were comparable between treatment groups (N=611; acoramidis, 409; placebo, 202). The estimated mean percentage of DLDCVH was 7.5% for acoramidis and 11.7% for placebo through Month 30 (Table). The treatment effect of acoramidis translated to a mean difference of 38 fewer DLDCVH vs placebo over 30 months (2.5 years; odds ratio of zero DLDCVH=2.02 [95% CI: 1.28-2.77]; p<0.001). The effect of acoramidis over 36 months (3 years) showed a mean difference (95% CI) of 65.1 (28.4-101.9) and 94.0 (48.0-139.9) fewer days vs placebo for the observed and modeled analyses, respectively.
Conclusions: In participants with ATTR-CM, acoramidis reduced DLDCVH vs placebo. Acoramidis preserved a mean of >1 month of time alive outside the hospital (38 days) over 30 months, extending to 65 days over 3 years using observed data and up to 94 days with modeled estimates, reflecting divergence in outcomes over time. This demonstrates acoramidis may reduce hospitalization-related healthcare costs, a key component of healthcare decision-making.