BridgeBio Pharma : BBIO-Acoramidis-ESC-HF2026-sTTR-variability

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

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

Insights From the ATTRibute-CM Trial

Duke University School of Medicine, Durham, NC, USA

Presented on 11 May 2026 at the Annual Congress of the Heart Failure Association of the European Society of Cardiology (ESC-HF), 9-12 May 2026; Barcelona, Spain

ATTR-CM is a progressive and potentially fatal disease caused by TTR destabilization1,2

Acoramidis is an oral TTR stabilizer that achieves near-complete (≥ 90%) TTR stabilization in vitro3-5

In ATTRibute-CM,6acoramidis increased mean sTTR by Day 28 at the trial level, predicting improved survival7

Longitudinal effects on sTTR variability at the individual level remain unknown

Within-participant variability may complement mean achieved sTTR concentrations as a marker of disease severity, risk, and treatment response

We hypothesized that lower sTTR variability may reflect more durable pharmacologic stabilization of sTTR

Purpose

To evaluate biological correlates of TTR variability

To understand the prognostic importance of intraindividual variation in sTTR beyond mean-achieved sTTR levels

To examine the effect of acoramidis on sTTR variability

Figure from Maurer MS, et al. J Am Coll Cardiol. 2025;85:1911-1923. https://www.jacc.org/doi/10.1016/j.jacc.2025.03.542 Creative Commons Attribution License (CC BY)

ATTR-CM, transthyretin amyloid cardiomyopathy; D, Day; M, Month; SE, standard error; sTTR, serum transthyretin; TTR, transthyretin.

1. Garcia-Pavia P, et al. Eur Heart J. 2021;42:1554-1568. 2. Ruberg FL, et al. JAMA. 2024;331:778-791. 3. Judge DP, et al. J Am Coll Cardiol. 2019;74:285-295.

BridgeBio Pharma, Inc. Prescribing Information, Attruby (acoramidis). FDA, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216540s000lbl.pdf.

Ji A, et al. J Cardiovasc Pharmacol. 2025;86:204-209. 6. Gillmore JD, et al. N Engl J Med. 2024;390:132-142. 7. Maurer MS, et al. J Am Coll Cardiol. 2025;85:1911-1923.

ATTRibute-CM compared acoramidis 800 mg HCl (n = 409) and placebo (n = 202) BID for 30 months (mITT populationa)

Tafamidis usage was allowed after Month 12

In this analysis, participants were included who:

Had ≥2 post-Day 28 sTTR values (between Day 28-Month 12) and were alive at Month 12 (N = 563/611) for landmark analysis

Had ≥2 post-Day 28 sTTR values between Day 28-Month 30 (N = 596/611) for treatment effect analysis

sTTR coefficient of variation (CVi)1 = standard deviation of sTTR concentration

mean sTTR concentration

A marker of within-participant sTTR variability

Lower sTTR CVi Less sTTR intraindividual

variability over time

aThe mITT population was the primary analysis population for efficacy endpoints in ATTRibute-CM and included randomized participants who had received ≥ 1 dose of study treatment, had ≥ 1 efficacy evaluation after baseline, and had a baseline eGFR of ≥ 30 mL/min/1.73 m2.

BID, twice daily; modified intention-to-treat; NT-proBNP, sTTR, serum transthyretin.

1. Gaba P, et al. J Am Coll Cardiol. 2025;85:550-553.

Baseline predictors of sTTR CVi evaluated using Chi-squared test, Welch's t-test, and Wilcoxon rank-sum test

Chi-squared tests to compare proportions of participants:

Maintaining sTTR levels ≥ thresholds (ranging from 15-40 mg/dL) between D28-M12 in acoramidis and placebo arms

Above/below sTTR thresholds between D28-M12 and subsequent mortality (M12-M30)

KM curves for 4 groups of mean achieved sTTR concentrations (above/below median) and sTTR CVi (above/below median), landmarked at 12 months

Multivariable-adjusted Cox regression landmark analysis at M12 to assess association between both sTTR CVi and mean-achieved sTTR levels with fatal outcomes

Adjusted for time-varying tafamidis initiation, 6MWD, age, sex, NYHA class, and BMI, while stratifying by treatment, genotype, eGFR, and NT-proBNP

Several sensitivity analyses assessing the robustness of CVi calculation and choice of landmark time

Treatment effect of acoramidis versus placebo on sTTR CVi D28-M30 using ANCOVA analysis

6MWD, 6-minute walk distance; ANCOVA, analysis of covariance; BMI, body mass index; eGFR, estimated glomerular filtration rate; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; sTTR, serum transthyretin; D, Day; M, Month

1. Gaba P, et al. J Am Coll Cardiol. 2025;85:550-553.

Baseline Characteristic

Low CVi (n = 282)

< population median

High CVi (n = 281)

> population median

p Value

Age, years, mean (SD)

76.9 (6.7)

77.1 (6.4)

0.654

Sex, male, n (%)

256 (90.8)

257 (91.5)

0.777

Wild-type ATTR-CM, n (%)

257 (91.1)

254 (90.4)

0.761

NAC stage, n (%)

0.001

195 (69.1)

150 (53.4)

68 (24.1)

105 (37.4)

III

19 (6.7)

26 (9.3)

6MWD, m, mean (SD)

374 (101)

356 (97)

0.033

BMI, kg/m2, mean (SD)

27.1 (3.7)

0.985

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

2030 (1068-3052)

2427 (1308-4115)

0.001

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

64 (17)

62 (18)

0.101

sTTR, mg/dL, mean (SD)

23.9 (4.9)

22.9 (6.2)

0.036

Number of sTTR measurements, median (Q1-Q3)

4 (4-5)

0.192

p values for categorical variables are based on the chi-square test; continuous variables are reported as mean (SD) with p values based on Welch's t-test, except for NT-proBNP (reported as median [Q1-Q3]), with the p value obtained using Wilcoxon rank sum test. Low CVi refers to CVi of post-D28 sTTR by M12 at or below the overall population median. High CVi refers to CVi of post-D28 sTTR by M12 above the overall population median. CVi Population median = 7.94%

6MWD, 6-minute walk distance; ATTR-CM, transthyretin amyloid cardiomyopathy; BMI, body mass index; CVi, intraindividual coefficient of variation; D, Day; eGFR, estimated glomerular filtration rate; M, Month; NAC, National Amyloidosis Centre; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; Q, quartile; SD, standard deviation; sTTR, serum transthyretin.

Mean sTTR Concentrations Through Month 30 by Treatment Group in ATTRibute-CM

Individual sTTR Concentrations by Treatment Arm and Tafamidis Initiation

aMean observed sTTR concentrations through Month 30 by treatment group in ATTRibute-CM.

M, Month; SE, standard error; sTTR, serum transthyretin; TTR, transthyretin. 6

Proportion of Participants Whose sTTR Stayed Equal to or Above Given

Thresholds (D28-M12) for Acoramidis Versus

Placebo

sTTR

Threshold

mg/dL

Acoramidis n = 378

n (%)

Placebo n = 185 n (%)

p Value

363 (96)

138 (75)

< 0.001

362 (96)

129 (70)

< 0.001

351 (93)

104 (56)

< 0.001

320 (85)

75 (41)

< 0.001

291 (77)

51 (28)

< 0.001

230 (61)

26 (14)

< 0.001

D, Day; M, Month; sTTR, serum transthyretin.

Proportion of Participants Surviving (M12-M30), as a Function of Whether sTTR Concentrations Always Stayed Equal to or Above Versus Ever Dropped Below Given Thresholds (D28-M12)a

sTTR

Threshold

mg/dL

Ever Dropped Below

n/N (%)

Equal to or Above n/N (%)

p Value

35/62 (56)

437/501 (87)

< 0.001

41/72 (57)

431/491 (88)

< 0.001

71/108 (66)

401/455 (88)

< 0.001

117/168 (70)

355/395 (90)

< 0.001

164/221 (74)

308/342 (90)

< 0.001

234/307 (76)

238/256 (93)

< 0.001

aParticipants surviving were also free of heart transplantation and implantation of a cardiac mechanical assist device. D, Day; M, Month; sTTR, serum transthyretin.

Landmark Analysis of ACM (M12-M30) by Mean sTTR Concentration and sTTR CVi

Groups (D28-M12) for the Overall Population

Data are for the overall modified intention-to-treat population. Participants were divided into those above (high) vs at/below (low) population median values of sTTR mean and CVi between D28-M12. ACM, all-cause mortality; CVi, intraindividual coefficient of variation; D, Day; M, Month; sTTR, serum transthyretin.

Summary of ACM or CVM (M12-30) by sTTR Mean Concentration and sTTR CVi Groups (D28-M12)

ACM, all-cause mortality; CVi, intraindividual coefficient of variation; CVM, cardiovascular-related mortality; D, Day; M, Month; sTTR, serum transthyretin.

Sensitivity analyses showed consistent results after accounting for the following:

Excluding participants with only 2 sTTR measurements

Adjusting for number of sTTR measurements in the full model

Adjusting for the change from baseline in sTTR at Day 28 in the full model

Shifting the landmark time from Month 12 to Month 6 in the full model

Model

sTTR Mean (High vs Low)

sTTR CVi (Low vs High)

HR (95% CI)

p Value

HR (95% CI)

p Value

Baseline sTTR

+ sTTR mean

0.42

(0.23, 0.77)

0.005

Baseline sTTR

+ sTTR CVi

0.59

(0.37, 0.94)

0.025

Baseline sTTR

+ sTTR mean + sTTR CVi

0.43

(0.23, 0.78)

0.006

0.61

(0.38, 0.96)

0.033

Full model*

0.46

(0.24, 0.85)

0.014

0.56

(0.35, 0.89)

0.014

*Full model additionally adjusted for time-varying tafamidis initiation, 6MWD, age, sex, NYHA class, and BMI; and stratified by treatment, genotype, baseline NT-proBNP levels, and baseline eGFR

aSequential landmark analyses with multivariable-adjusted Cox proportional hazards models. For sTTR mean concentration (D28-M12) and sTTR CVi (D28-M12), high vs low was defined as > vs ≤ the median, respectively. The Cox proportional hazards model was stratified by treatment group and the 3 randomization stratification factors (genotype, baseline NT-proBNP levels, and baseline eGFR). Tafamidis initiation status was set as a time-varying covariate.

6MWD, 6-minute walk distance; ACM, all-cause-mortality; BMI, body mass index; CI, confidence interval; CVi, intraindividual coefficient of variation; D, Day; eGFR, estimated glomerular filtration rate; HR, hazard ratio; M, Month; N/A, not applicable; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; sTTR, serum transthyretin.

Distribution of sTTR CVi by Treatment Group

p < 0.001

Results were consistent from Day 28 through Month 12 (before tafamidis initiation allowed)

Reducing sTTR variability accounted for 20% of the acoramidis effect on ACM

Percentage reduction in CVi (95% CI) for acoramidis vs placebo is shown for the overall population and by subgroups of age, sex, race, genotype, NT-proBNP, eGFR, NAC stage, and NYHA class.

CI, confidence interval; CVi, intraindividual coefficient of variation; eGFR, estimated glomerular filtration rate; NAC, National Amyloidosis Centre; no., number; NT-proBNP, N-terminal pro-B-type

natriuretic peptide; NYHA, New York Heart Association; sTTR, serum transthyretin. 13

Higher intraindividual sTTR variability (CVi) was associated with higher-risk clinical features

Maintaining sTTR levels above physiologic thresholds was associated with reduced ACM risk

Having both low sTTR variability (CVi) and high sTTR levels was independently associated with the lowest risk for fatal events

Results consistent after comprehensive multivariable adjustment including baseline sTTR levels and change in sTTR

Acoramidis significantly decreased sTTR variability compared with placebo

Consistency observed across all pre-specified trial subgroups

Limitations: Landmark analysis required survival to Month 12; residual confounding

ACM, all-cause mortality; ATTR-CM, transthyretin amyloid cardiomyopathy; sTTR, serum transthyretin; TTR, transthyretin.

The authors would like to thank the patients who participated in the ATTRibute-CM trial and their families

The authors would also like to thank the ATTRibute-CM investigators

This study was funded by BridgeBio Pharma, Inc.

Under the guidance of the authors, medical writing assistance was provided by Benjamin Levine PhD of Oxford PharmaGenesis, and was funded by BridgeBio Pharma, Inc.

Editorial support and critical review were provided by Souhiela Fawaz PhD of BridgeBio Pharma, Inc.

Disclaimer

BridgeBio Pharma Inc. published this content on May 11, 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.