BridgeBio Pharma : BBIO-Acoramidis-ESC-HF2026 NT-proBNP-subgroups

Published: 2026-05-11 11:07:11 ET BBIO

Published on 05/11/2026 at 11:07 am EDT

Acoramidis Treatment Attenuates the Rise in N-Terminal Pro-B-Type Natriuretic Peptide From Baseline to Month 30 Compared With Placebo Across Participant Subgroups in ATTRibute-CM

Prem Soman,1Nitasha Sarswat,2Ahmad Masri,3Kunal Bhatt,4 Marianna Fontana,5Pablo Garcia-Pavia,6,7Olakunle Akinboboye,8Richard K. Cheng,9Chris Chen,10Jean-François Tamby,10Jonathan C. Fox,10Julian D. Gillmore,5Daniel P. Judge,11James L. Januzzi Jr,12and Michel G. Khouri13

1Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2University of Chicago Medicine, Chicago, IL, USA; 3Division of Cardiology, Oregon Health and Science University, Portland, OR, USA; 4Emory University, School of Medicine, Atlanta, GA, USA; 5National Amyloidosis Centre, University College London, Royal Free Hospital, London, UK; 6Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain; 7Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; 8Laurelton Heart Specialists PC, Rosedale, NY, USA; 9University of Washington, Seattle, WA, USA; 10BridgeBio Pharma, Inc., San Francisco, CA, USA; 11Division of Cardiology, Medical University of South Carolina, Charleston, SC, USA; 12Division of Cardiology, Massachusetts General Hospital, Baim Institute for Clinical Research, Boston, MA, USA; 13Duke University School of Medicine, Durham, NC, USA

CONCLUSIONS

To evaluate the effect of acoramidis on N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration across participant subgroups in a post hoc analysis of the ATTRibute-CM study (NCT03860935)

PURPOSE

In ATTRibute-CM, acoramidis consistently blunted the 30-month increase in NT-proBNP concentrations by approximately 50% across all participant subgroups assessed, including those with advanced disease, compared with placebo

These data demonstrate the robust efficacy of acoramidis on NT-proBNP, a key marker of ATTR-CM disease progression

Furthermore, the efficacy of acoramidis on NT-proBNP concentrations, compared with placebo, was demonstrated independently of concomitant tafamidis use

BACKGROUND

RESULTS

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative, restrictive,

life-threatening, and progressive disease caused by destabilized transthyretin (TTR) tetramers and subsequent accumulation of amyloid fibrils in the interstitial space of the myocardium1-6

Overall, 611 participants were included in the mITT population; baseline demographics and characteristics were generally well balanced between the treatment groups (Table 1)

Baseline NT-proBNP concentrations for each subgroup are shown in Table 2

NT-proBNP is a biomarker of disease progression, and a progressive rise in its concentration is associated with increased mortality7

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-CM8-13

In the 30-month, phase 3 ATTRibute-CM study,14acoramidis treatment significantly attenuated the rise in NT-proBNP concentrations compared with placebo (p< 0.0001)

Additionally, at Month 30, 45% of acoramidis recipients who had NT-proBNP data available at both baseline and Month 30 experienced a net decrease from baseline in their NT-proBNP concentrations, compared with 9% of those receiving placebo

The effect of acoramidis on the rise in NT-proBNP concentrations across different patient subgroups has not been fully elucidated

In total, 595 randomized participants (acoramidis, n = 397; placebo, n = 198) were included in the Month 30 analysis

p Value for Treatment Effect

METHODS

The ATTRibute-CM study design has been described previously14

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 of NT-proBNP concentrations were assessed in the modified intention-to-treat (mITT) population, which included all randomized participants who received at least one dose of acoramidis or placebo, had at least one efficacy evaluation after baseline, and had a baseline estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2

The adjusted geometric mean (AGM) fold change from baseline to Month 30 in NT-proBNP concentrations was analysed in the acoramidis and placebo treatment groups using a mixed effects model for repeated measures after log transformation of NT-proBNP concentrations

Missing measurements due to early discontinuation of study drug were imputed using the jump to reference method. Missing measurements due to death were imputed by sampling with replacement from the worst 5% of observed values

The AGM fold change ratio (acoramidis vs placebo) was calculated for the following

pre-specified participant subgroups: ATTR-CM genotype (wild-type vs variant), 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)

The change from baseline to Month 30 in NT-proBNP concentrations in participants who completed the study and who received acoramidis alone or placebo alone (i.e. did not receive open-label concomitant tafamidis during the study) was also assessed

aTTR genotype was reported at randomization.

Participants included in the Month 30 analysis, n

NT-proBNP Concentration, pg/mL, Mean (SD)

Acoramidis (n = 409)

Placebo (n = 202)

397

198

ATTR-CM genotypeb

ATTRv-CM

2775.4 (1971.3)

2788.8 (1964.7)

ATTRwt-CM

2874.8 (2169.8)

2634.9 (1897.1)

NT-proBNP

≤ 3000 pg/mL

1714.2 (955.7)

1597.9 (937.8)

> 3000 pg/mL

5053.3 (2089.8)

4678.3 (1618.1)

eGFR

< 45 mL/min/1.73 m2

4063.2 (2350.3)

3693.1 (2273.4)

≥ 45 mL/min/1.73 m2

2639.0 (2035.4)

2475.3 (1777.9)

Age

< 78 years

2617.0 (1988.3)

2344.3 (1767.6)

≥ 78 years

3098.4 (2270.8)

2955.9 (1984.7)

Country

USA

2991.1 (2434.4)

2750.9 (1850.9)

Rest of world

2836.2 (2081.0)

2623.7 (1916.8)

NYHA functional class

I or II

2724.5 (2104.3)

2520.7 (1845.1)

III

3547.5 (2250.0)

3422.4 (2065.7)

aData shown here are for participants included in the Month 30 analysis (N = 595). bTTR genotype was reported at randomization.

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)

Pre-specified subgroups

ATTR-CM genotype,an (%)

ATTRv-CM

39 (9.5)

20 (9.9)

ATTRwt-CM

370 (90.5)

182 (90.1)

NT-proBNP, n (%)

≤ 3000 pg/mL

268 (65.5)

133 (65.8)

> 3000 pg/mL

141 (34.5)

69 (34.2)

eGFR, n (%)

< 45 mL/min/1.73 m2

65 (15.9)

29 (14.4)

≥ 45 mL/min/1.73 m2

344 (84.1)

173 (85.6)

Age, n (%)

< 78 years

198 (48.4)

101 (50.0)

≥ 78 years

211 (51.6)

101 (50.0)

Country, n (%)

USA

77 (18.8)

42 (20.8)

Rest of world

332 (81.2)

160 (79.2)

NYHA functional class, n (%)

I or II

339 (82.9)

173 (85.6)

III

70 (17.1)

29 (14.4)

In all participant subgroups assessed, the NT-proBNP AGM fold change ratio from baseline to Month 30 favoured acoramidis over placebo (all p< 0.001), with minimal heterogeneity of treatment effect noted among subgroups ( Figure 1)

During the study, 348 participants received acoramidis alone and 156 received placebo alone; data on NT-proBNP concentrations at Month 30 were available for 232 of those receiving acoramidis and for 98 of those receiving placebo

In participants who completed the study and who received acoramidis alone, the median (Q1, Q3) change from baseline in NT-proBNP concentrations at Month 30 was 86 (−431, 617) pg/mL, compared with 1135 (440, 2634) pg/mL in those who received placebo alone (Figure 2)

595 (100.0)

ATTRv-CM ATTRwt-CM

≤ 3000 pg/mL

> 3000 pg/mL

59 (9.9)

536 (90.1)

0.6070

388 (65.2)

207 (34.8)

0.9729

< 45 mL/min/1.73 m294 (15.8)

≥ 45 mL/min/1.73 m2501 (84.2)

0.1296

< 78 years

≥ 78 years Country USA

Rest of world

I or II III

290 (48.7)

305 (51.3)

0.5079

116 (19.5)

479 (80.5)

0.7777

497 (83.5)

98 (16.5)

0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2

Acoramidis Alone

(n = 232)

Placebo Alone

(n = 98)

3000

2500

2000

1500

1000

500

0

−500

−1000

aData are shown for participants who did not receive concomitant tafamidis after Month 12 and had data available at baseline and Month 30 (N = 330).

REFERENCES: 1. Rapezzi C, et al. Nat Rev Cardiol. 2010;7(7):398-408. 2. Ruberg FL, et al. JAMA. 2024;331(9):778-791. 3. Lane T, et al. Circulation. 2019;140(1):16-26. 4. Ruberg FL, et al. J Am Coll Cardiol. 2019;73(22):2872-2891. 5. Grogan M, et al. J Am Coll Cardiol. 2016;68(10):1014-1020.

6. Jain A, Zahra F. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2023. Transthyretin Amyloid Cardiomyopathy (ATTR-CM) [Updated 27 April 2023]. Accessed 12 March 2026. https://www.ncbi.nlm.nih.gov/books/NBK574531/. 7. Garcia-Pavia P, et al. Eur J Heart Fail. 2021;23(6):895-905.

8. Judge DP, et al. J Am Coll Cardiol. 2019;74(3):285-295. 9. BridgeBio Pharma, Inc. Prescribing Information, Attruby (acoramidis). FDA, 2024. Accessed 12 March 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216540s000lbl.pdf. 10. BridgeBio Europe B.V. SmPC, Beyonttra (acoramidis).

EMA, 2025. Accessed 12 March 2026. https://www.ema.europa.eu/en/documents/product-information/beyonttra-epar-product-information_en.pdf.

11. Alexion. SmPC, Beyonttra (acoramidis). MHLW Japan, 2025. Accessed 12 March 2026. https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ ResultDataSetPDF/870056_2190048F1029_1_01. 12. Bayer plc. SmPC, Beyonttra (acoramidis). MHRA UK, 2025. Accessed 02 April 2026. https://mhraproducts4853.blob.core.windows.net/docs/65cdc303a1411fa20142875b65739fad8ac72058. 13. Bayer (Switzerland) AG. Approval summary, Beyonttra (acoramidis). Swissmedic, 2025. Accessed 12 March 2026. https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/ authorisations/new-medicines/beyonttra-filmtabletten-acoramidisum.html. 14. Gillmore JD, et al. N Engl J Med. 2024;390(2):132-142. FUNDING: This study was sponsored by BridgeBio Pharma, Inc., San Francisco, CA, USA.

Oxford PharmaGenesis and was funded by BridgeBio Pharma, Inc. Editorial support and critical review were provided by Souhiela Fawaz, PhD, and Shweta Rane, PhD, CMPP, BCMAS, of BridgeBio Pharma, Inc.

Disclaimer

BridgeBio Pharma Inc. published this content on May 10, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 11, 2026 at 15:06 UTC.