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

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

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

Consistent Benefit on Kansas City Cardiomyopathy Questionnaire Overall Summary Score With Acoramidis Treatment Compared With Placebo Across Participant Subgroups in ATTRibute-CM

Marianna Fontana,1 Efstathios Kastritis,2 Joshua D. Mitchell,3 Jan Krejci,4,5 Peter van der Meer,6 Heather Falvey,7 Chris Chen,7 Jean-François Tamby,7 Jonathan C. Fox,7 Suresh Siddhanti,7 Francesco Cappelli,8 Ahmad Masri,9 Pablo Garcia-Pavia,10,11 John A. Spertus,12 and Brett W. Sperry12

1National Amyloidosis Centre, University College London, Royal Free Hospital, London, UK; 2Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece; 3Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA; 4Department of Cardiovascular Diseases, St. Anne's University Hospital in Brno, Brno, Czech Republic; 5Masaryk University, Brno, Czech Republic; 6Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; 7BridgeBio Pharma, Inc., San Francisco, CA, USA; 8Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy; 9Division of Cardiology, Oregon Health and Science University, Portland, OR, USA; 10Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain; 11Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; 12Saint Luke's Mid America Heart Institute, Kansas City, MO, USA

CONCLUSIONS

To evaluate the effect of acoramidis on heart failure-related health status as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score across participant subgroups from the ATTRibute-CM study (NCT03860935)

PURPOSE

BACKGROUND

RESULTS

Transthyretin amyloid cardiomyopathy (ATTR-CM), an infiltrative, restrictive, life-threatening, and progressive disease caused by destabilized transthyretin (TTR) tetramers, is associated with impaired health status (symptoms, function, and quality of life)1-3

Baseline demographics and characteristics were generally well balanced between the treatment groups (Table 1)

The KCCQ measures a patient's perspective of their heart failure-related health status4

Acoramidis, an oral TTR stabilizer that achieves near-complete (≥ 90%) TTR stabilization, is approved in the USA, the European Union, Japan, the UK, and Switzerland for the treatment of adults with ATTR-CM5-10

In the phase 3 ATTRibute-CM study, acoramidis treatment markedly attenuated the decline in KCCQ-OS score through Month 30 compared with placebo (least-squares mean difference: 9.9 points; 95% confidence interval [CI]: 5.97-13.91; p< 0.0001) 11

The consistency of this benefit across clinically relevant patient subgroups has not been fully characterized

p Value

METHODS

The ATTRibute-CM study design has been described previously11

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

At Month 30, the least-squares mean change from baseline difference between treatment groups in KCCQ-OS score was estimated using a mixed effects model for repeated measures

A pre-specified sensitivity analysis was performed, which excluded all participants who received concomitant tafamidis at any time during the study

Efficacy analyses at Month 30 were performed in the following pre-specified subgroups: ATTR-CM genotype (wild-type vs variant), N-terminal pro-B-type natriuretic peptide (NT-proBNP; ≤ 3000 vs

> 3000 pg/mL), eGFR (≥ 45 vs < 45 mL/min/1.73 m²), age (< 78 vs ≥ 78 years), country (USA vs rest of world), and New York Heart Association (NYHA) functional class (I/II vs III)

Limitations: The ATTRibute-CM study population had a relatively low proportion of some subgroups (e.g. women, African American individuals, participants with variant ATTR-CM), which may have affected the health status outcomes reported here

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

The sensitivity analysis, excluding participants who received concomitant tafamidis, demonstrated a clinically meaningful benefit favouring treatment with acoramidis alone at Month 30 versus placebo

(least-squares mean difference between treatment groups: 9.7 points [95% CI: 5.26-14.13]; p< 0.0001; Table 2)

Baseline (observed values)

mITT Population

Sensitivity Analysis

Acoramidis (n = 409)

Placebo (n = 202)

Acoramidis (n = 348)

Placebo (n = 156)

n

408

202

347

156

Mean (SD)

71.7 (19.4)

70.5 (20.7)

71.3 (19.5)

68.9 (21.8)

Month 30 (change from baseline)

n

405

201

345

155

Least-squares mean (SE)

−11.5 (1.18)

−21.4 (1.65)

−12.9 (1.27)

−22.6 (1.88)

Least-squares

mean difference (SE)a

9.9 (2.02)

9.7 (2.26)

95% CI

5.97-13.91

5.26-14.13

p value

< 0.0001

< 0.0001

aDifference expressed as acoramidis - placebo.

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 (%)

I

51 (12.5)

17 (8.4)

II

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)

eGFR, mL/min/1.73 m2, mean (SD)

62.0 (17.4)

62.5 (17.5)

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)

The mixed effects model for repeated measures analysis included treatment group, visit, ATTR-CM genotype (wild-type vs variant), NT-proBNP concentration (≤ 3000 vs > 3000 pg/mL), eGFR

(≥ 45 vs < 45 mL/min/1.73 m²), and the treatment group-by-visit interaction as factors, and baseline KCCQ-OS score as a covariate. Randomization stratification factors of ATTR-CM genotype, NT-proBNP, and eGFR were based on information from the interactive voice/web response system.

The benefit of acoramidis on KCCQ-OS score through Month 30 was observed across all pre-specified participant subgroups versus placebo, with no evidence of treatment-effect heterogeneity (Figure 1)

- p values were significant (< 0.05) in each participant subgroup except for eGFR < 45 mL/min/1.73 m² and NYHA functional class III, which both favoured acoramidis over placebo but were limited by small participant numbers

117 (19)

489 (81)

298 (49)

308 (51)

398 (66)

208 (34)

606 (100)

Variant 59 (10)

Wild-type 547 (90)

0.002

< 0.001

≤ 3000 pg/mL

> 3000 pg/mL

< 0.001

0.001

< 45 mL/min/1.73 m2 93 (15)

≥ 45 mL/min/1.73 m2 513 (85)

0.405

< 0.001

< 78 years

≥ 78 years

< 0.001

0.008

USA

Rest of world

0.019

< 0.001

I or II 507 (84)

III 99 (16)

< 0.001

0.253

−10 −5 0 5 10 15 20 25 30 35

p values indicated with * are from testing the interaction of the subgroup and treatment; other

p values are from testing the treatment difference at the given value of the subgroup variable.

aData are from participants with available values. bTTR genotype was reported at randomization.

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4. Green CP, et al. J Am Coll Cardiol. 2000;35(5):1245-1255. 5. Judge DP, et al. J Am Coll Cardiol. 2019;74(3):285-295. 6. BridgeBio Pharma, Inc. Prescribing Information, Attruby (acoramidis). FDA, 2024. Accessed 13 March 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2024/216540s000lbl.pdf. 7. BridgeBio Europe B.V. SmPC,

Beyonttra (acoramidis). EMA, 2025. Accessed 13 March 2026. https://www.ema.europa.eu/en/documents/product-information/ beyonttra-epar-product-information_en.pdf.

8. Alexion. SmPC, Beyonttra (acoramidis). MHLW Japan, 2025. Accessed 13 March 2026. www.pmda.go.jp/ PmdaSearch/iyakuDetail/ResultDataSetPDF/870056_2190048F1029_1_01. 9. 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. 10. Bayer plc. SmPC, Beyonttra (acoramidis). MHRA UK, 2025. Accessed 1 April 2026. https://mhraproducts4853.blob.core.windows. net/docs/65cdc303a1411fa20142875b65739fad8ac72058. 11. Gillmore JD, et al. N Engl J Med. 2024;390(2):132-142.

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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.