BridgeBio Pharma : BBIO-Acoramidis-ESC-HF2026 KCCQ-improvement

Published: 2026-05-11 11:09:09 ET BBIO

Published on 05/11/2026 at 11:09 am EDT

Effect of Acoramidis on Improvement or Maintenance of Heart Failure-Related Health Status as Assessed by Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in ATTRibute-CM

Charles F. Sherrod,1,2 John A. Spertus,1,2 Marianna Fontana,3 Joshua D. Mitchell,4 James M. Tauras,5 Heather Falvey,6 Chris Chen,6 Jean-François Tamby,6 Jonathan C. Fox,6 Suresh Siddhanti,6 Francesco Cappelli,7 Mazen Hanna,8 and Brett W. Sperry1,2

1Healthcare Institute for Innovations in Quality, University of Missouri-Kansas City, Kansas City, MO, USA; 2Saint Luke's Mid America Heart Institute, Kansas City, MO, USA; 3National Amyloidosis Centre, University College London, Royal Free Hospital, London, UK; 4Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA;

5Montefiore Medical Center, Bronx, NY, USA; 6BridgeBio Pharma, Inc., San Francisco, CA, USA; 7Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy; 8Cleveland Clinic, Cleveland, OH, USA

CONCLUSIONS

To integrate survival and heart failure-related health status, as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score, into a single analysis to describe the efficacy of acoramidis on outcomes in participants from the ATTRibute-CM study (NCT03860935)

PURPOSE

BACKGROUND

RESULTS

Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by worsening heart failure, leading to impaired quality of life, hospitalizations, and often death1,2

A primary goal in managing ATTR-CM is to slow disease progression to preserve or improve patients' symptoms, function, and quality of life

The KCCQ measures a patient's perspective of their heart failure-related health status3

Acoramidis, an oral transthyretin (TTR) stabilizer that achieves near-complete (≥ 90%) TTR stabilization, is approved in the USA,

Baseline demographics and characteristics were generally well balanced between the treatment groups (Table 2) TABLE 2: Baseline Demographics and Characteristics; mITT Population (N = 611)

Alive and Well

At Month 30, more acoramidis recipients were 'alive and well' than placebo recipients (difference: 14.4%; Figure 2)

Age, years, mean (SD)

Acoramidis (n = 409)

Placebo (n = 202)

77.3 (6.5)

77.0 (6.7)

Sex, male, n (%)

374 (91.4)

181 (89.6)

Wild-type ATTR-CM,a n (%)

370 (90.5)

182 (90.1)

NYHA functional class, n (%)

51 (12.5)

17 (8.4)

288 (70.4)

156 (77.2)

III

70 (17.1)

29 (14.4)

6MWD,b m, mean (SD)

362.8 (103.5)

351.5 (93.8)

NT-proBNP, pg/mL, median (Q1-Q3)

2273 (1315-3872)

2274 (1128-3590)

Serum TTR,c mg/dL, mean (SD)

23.0 (5.6)

23.6 (6.1)

KCCQ-OS score,d mean (SD)

71.7 (19.4)

70.5 (20.7)

OR = 1.9 (95% CI: 1.3-2.8)

the European Union, Japan, the UK, and Switzerland for the treatment of adults with ATTR-CM4-9

In the phase 3 ATTRibute-CM study, acoramidis demonstrated a favourable trend toward reduced all-cause mortality (ACM) through Month 30 compared with placebo10,11

Acoramidis also significantly attenuated the decline in KCCQ-OS score through Month 30 (least-squares mean difference: 9.9 points; 95% confidence interval [CI]: 6.0-13.9; p< 0.001), 10 and a higher proportion of participants experienced an improvement in KCCQ-OS score (net increase from baseline) with acoramidis (31%) than with placebo (18%)

METHODS

Because the analysis of KCCQ-OS score at Month 30 can only be assessed in survivors, an approach integrating death and KCCQ-OS score is needed to better characterize the overall treatment benefit and support clinical decision-making

The ATTRibute-CM study design has been described previously10

- Briefly, eligible adult participants (≤ 90 years old) were randomized 2:1 to receive acoramidis HCl 800 mg or placebo

aTTR genotype was reported at randomization. bAcoramidis, n = 407. cAcoramidis, n = 406; placebo, n = 199. dAcoramidis, n = 408.

Alive and Not Worse

Alive and Better

NNT = 7 (95% CI: 4.5-16.2)

n = 59

n = 168

p = 0.001

KCCQ-OS > 60 and < 10-point decrease

twice daily for 30 months; concomitant tafamidis use was permitted after Month 12 at the discretion of the investigator

Efficacy analyses were conducted in the modified intention-to-treat (mITT) population, defined as all randomized participants who received at least one dose of acoramidis or placebo, had at least one post-baseline efficacy assessment, and had a baseline estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2

To integrate survival and health status into a single analysis, at Month 30 the effect of acoramidis on KCCQ-OS score was

At Month 30, the proportion of participants who were 'alive and not worse' significantly favoured acoramidis versus placebo

(difference: 16.8% using a cut-off of < 5-point decrease; 14.1% using a cut-off of < 10-point decrease; Figure 1)

OR = 1.8 (95% CI: 1.3-2.6)

At Month 30, the proportion of participants who were 'alive and better' significantly favoured acoramidis versus placebo

(difference: 11.5% using a cut-off of > 5-point increase; 7.3% using a moderate > 10-point improvement cut-off; Figure 3)

compared with placebo as participants 'alive and not worse', those 'alive and well', and those 'alive and better' (Table 1) using a Cochran-Mantel-Haenszel test with stratification factors of TTR genotype (wild-type versus variant), N-terminal pro-B-type

natriuretic peptide (NT-proBNP) concentration, and eGFR; numbers needed to treat (NNTs) with 95% CIs were calculated as 60

the inverse of the absolute risk reductions and their 95% CIs, using the Mantel-Haenszel method

Participants with a missing change from baseline value for KCCQ-OS score who were alive at Month 30 were excluded from

the analysis. Participants who experienced ACM by Month 30 were also excluded 40

Outcome

Definition

Alive and not worse (two thresholds examined)

Alive and a decrease from baseline in KCCQ-OS score of either < 5 or < 10 points

Alive and well

Alive and KCCQ-OS score of > 60 with a decrease from baseline of < 10 points

Alive and better (two thresholds examined)

Alive and an increase from baseline in KCCQ-OS score of either > 5 or > 10 points

Limitations: KCCQ-OS scores were analysed only for participants who survived to Month 30, which may have skewed the analyses

OR = 2.1 (95% CI: 1.4-3.1)

p < 0.001

Placebo

n = 56

n = 73

n = 171

n = 194

NNT = 6 (95% CI: 4.0-11.6)

< 5-point decrease

NNT = 8 (95% CI: 4.5-18.3)

p = 0.002

< 10-point decrease

Placebo

OR = 2.1 (95% CI: 1.3-3.4)

NNT = 9 (95% CI: 5.5-20.4)

p = 0.002

OR = 2.0 (95% CI: 1.1-3.6)

NNT = 14 (95% CI: 7.8-53.4)

p = 0.016

n = 16

n = 26

n = 58

n = 93

5-point increase

10-point increase

towards those with better health status

CORRESPONDING AND PRESENTING AUTHOR: Charles F. Sherrod, [email protected]

REFERENCES: 1. Eldhagen P, et al. ESC Heart Failure. 2023;10(3):1871-1882. 2. Ruberg F, Maurer MS. JAMA. 2024;331(9):778-791. 3. Green CP, et al. J Am Coll Cardiol. 2000;35(5):1245-1255. 4. Judge DP, et al. J Am Coll Cardiol. 2019;74(3):285-295. 5. BridgeBio Pharma, Inc. Prescribing Information, Attruby (acoramidis). FDA, 2024. Accessed 13 March 2026. www.accessdata.fda.gov/drugsatfda_docs/ label/2024/216540s000lbl.pdf. 6. BridgeBio Europe B.V. SmPC, Beyonttra (acoramidis). EMA, 2025. Accessed 13 March 2026. www.ema.europa.eu/en/documents/product-information/beyonttra-epar-product-information_en.pdf. 7. Alexion. SmPC, Beyonttra (acoramidis). MHLW Japan, 2025. Accessed 13 March 2026. www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/870056_2190048F1029_1_01.

8. Bayer (Switzerland) AG. Approval summary, Beyonttra (acoramidis). Swissmedic, 2025. Accessed 13 March 2026. www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/authorisations/new-medicines/beyonttra-filmtabletten-acoramidisum.html. 9. Bayer plc. SmPC, Beyonttra (acoramidis). MHRA UK, 2025. Accessed 1 April 2026. https://mhraproducts4853.blob.core.windows.net/ docs/65cdc303a1411fa20142875b65739fad8ac72058. 10. Gillmore JD, et al. N Engl J Med. 2024;390(2):132-142. 11. Judge DP, et al. J Am Coll Cardiol. 2025;85(10):1003-1014.

FUNDING: This study was sponsored by BridgeBio Pharma, Inc., San Francisco, CA, USA.

ABBREVIATIONS: 6MWD, 6-minute walk distance; ACM, all-cause mortality; ATTR-CM, transthyretin amyloid cardiomyopathy; CI, confidence interval; eGFR, estimated glomerular filtration rate; KCCQ-OS, Kansas City Cardiomyopathy Questionnaire Overall Summary; mITT, modified intention-to-treat; NNT, number needed to treat; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; OR, odds ratio; Q1, first quartile; Q3, third quartile; SD, standard deviation; TTR, transthyretin.

ACKNOWLEDGEMENTS: Under the direction of the authors, medical writing assistance was provided by Anson Shek, PhD, of Oxford PharmaGenesis and was funded by BridgeBio Pharma, Inc. Editorial support and critical review were provided by Dana Walters, PhD, and Shweta Rane, PhD, CMPP, BCMAS, of BridgeBio Pharma, Inc.

Disclaimer

BridgeBio Pharma Inc. published this content on May 09, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 11, 2026 at 15:08 UTC.