BridgeBio Pharma : BBIO-Acoramidis-ESC-HF2026 MAIC

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

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

Anchored Matching-Adjusted Indirect Comparison of Acoramidis (ATTRibute-CM) vs Tafamidis (ATTR-ACT) for Risk of Cardiovascular-Related Hospitalization, All-Cause Mortality, and Safety in ATTR-CM

Emer Joyce,1,2Ahmad Masri,3Zubair Shah,4Kuangnan Xiong,5Stanimira Krotneva,6Irina Proskorovsky,6Anina Fraschke,7Maria Huelsebeck,7Liana Hennum,5Jean François Tamby,5Heather Falvey,5Antoine Jobbé-Duval,8and Kevin Alexander9

1Department of Cardiology, Mater Misericordiae University Hospital, Dublin, Ireland; 2School of Medicine, University College Dublin, Dublin, Ireland; 3Division of Cardiology, Oregon Health and Science University, Portland, OR, USA; 4Division of Cardiology, The University of Kansas Health System, Kansas City, KS, USA; 5BridgeBio Pharma, Inc.,

San Francisco, CA, USA; 6PPD Evidera Health Economics & Market Access, Thermo Fisher Scientific, Waltham, MA, USA; 7Bayer, Berlin, Germany; 8Department of Cardiology, Médipôle Hôpital Mutualiste, Villeurbanne, France; 9Stanford Amyloid Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA

CONCLUSIONS

To conduct a placebo-anchored, matching-adjusted indirect comparison (MAIC) to compare acoramidis with tafamidis 80 mg for the risk of cardiovascular-related hospitalization (CVH) and all-cause mortality (ACM) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM)

PURPOSE

BACKGROUND

METHODS

RESULTS

ATTR-CM is a progressive cardiomyopathy caused by deposition of destabilized, misfolded transthyretin (TTR) as amyloid fibrils in the heart1

Patients with ATTR-CM develop progressive heart failure, resulting in recurrent CVH, worsening functional status, and often death1,2

Acoramidis and tafamidis are TTR stabilizers approved for the treatment of adults with ATTR-CM in the USA, the European Union, and various other countries3-10

No head-to-head trials exist, and unadjusted indirect comparisons are not appropriate due to differences in enrolment criteria and imbalances between populations that can affect the response to treatment

Although the ATTRibute-CM and ATTR-ACT study designs were similar, ATTRibute-CM was conducted more recently (Table 1)

Due to improvements in supportive care and time to diagnosis, participants enrolled in ATTRibute-CM tended to have less-advanced disease than those enrolled in ATTR-ACT, potentially impacting efficacy outcomes relative to the placebo group11,12

An anchored MAIC can reduce bias from cross-trial heterogeneity by reweighting individual participant data (IPD) from the index trial to match aggregate data from the comparator trial, using placebo arms

In accordance with established methods and guidelines,13an anchored MAIC was conducted to estimate the comparative efficacy of acoramidis (ATTRibute-CM; index trial) versus tafamidis 80 mg (ATTR-ACT; comparator trial) (Figures 1 and 2)

Inclusion criteria matching of ATTRibute-CM to ATTR-ACT was done by excluding participants with NT-proBNP level < 600 pg/mL and/or eGFR < 25 mL/min/1.73 m2

Potential treatment effect modifiers (EMs) were pre-specified before data analysis based on published evidence and clinical expert input

EMs included age, TTR genotype (variant vs wild-type), New York Heart Association (NYHA) functional class, NT-proBNP level, and eGFR

Comparative efficacy was assessed for ACM and the annualized frequency of CVH over 30 months, using similar definitions for both trials

Data after initiation of concomitant tafamidis, which was allowed after Month 12 in ATTRibute-CM at the discretion of the investigator, were excluded to avoid potential confounding

To assess the robustness of the results, sensitivity analyses for CVH and ACM were conducted without censoring for concomitant tafamidis and with matching on baseline medication and pacemaker use

Matching resolved imbalances in treatment EMs. Post-matching baseline demographics and clinical characteristics in ATTRibute-CM and ATTR-ACT were well balanced (Table 2)

The post-matching effective sample size (ESS) was 209 for acoramidis and 89 for placebo in ATTRibute-CM (Table 2)

Placebo anchor validation: After matching, the Kaplan-Meier curves for ACM in the placebo arms overlapped between trials, demonstrating population alignment for the anchored comparison (Figure 3)

Adjusting for all potential EMs and excluding concomitant tafamidis use, acoramidis was associated with a statistically significant 34% relative risk reduction in the cumulative frequency of CVH versus tafamidis 80 mg (relative risk ratio [RRR]: 0.66; 95% confidence interval [CI]: 0.46-0.95) (Figure 4)

For ACM, after matching, results showed a non-statistically significant 28% hazard reduction versus tafamidis 80 mg (hazard ratio [HR]: 0.72; 95% CI: 0.41-1.26) (Figures 3 and 4)

Across the pre-specified sensitivity analyses, findings were consistent with the base-case MAIC analysis (Table 3)

Safety was comparable between treatments

as the common anchor, and resulting in a matched population that balances important differences in baseline characteristics (Figure 1)

For safety, no EMs were identified. Naive Bucher indirect treatment comparisons were conducted with and without censoring for concomitant tafamidis

0.719 (0.409-1.264)

Unadjusted Populations

Eligibility Matched Populations

MAIC-Weighted Populations

IPD

Aggregate data

MAIC

Acoramidis

Tafamidis 80 mg

IPD from ATTRibute-CM

weighted to match published aggregate data for ATTR-ACT

Placebo

Age, years

ATTRibute-CM (Matched) ATTR-ACT

Acoramidis (ESS = 209)

Placebo (ESS = 89)

Tafamidis 80 mg

(n = 176)

Placebo (n = 177)

Median (min, max)

76 (50, 88)

75 (55, 89)

76 (46, 88)

74 (51, 89)

< 65, %

9.1

8.5

9.1

8.5

≥ 65, %

90.9

91.5

90.9

91.5

ATTR-CM genotype, %

Variant

23.9

24.3

23.9

24.3

Wild-type

76.1

75.7

76.1

75.7

NYHA functional class, %

9.1

7.3

9.1

7.3

59.7

57.1

59.7

57.1

III

31.2

35.6

31.2

35.6

NT-proBNP, pg/mL

Mean (SD)

3900 (2100)

3800 (1600)

3900 (3100)

3800 (3000)

Median (min, max)

3100 (400, 15 700)

3200 (500, 8800)

3100 (400, 22 000)

3200 (300, 16 800)

Published aggregate data from ATTR-ACT

ATTRibute-CM

Acoramidis

ATTR-ACT

Tafamidis 80 mg

ATTRibute-CM

Acoramidis

ATTR-ACT

Tafamidis 80 mg

ATTRibute-CM

Acoramidis

ATTR-ACT

Tafamidis 80 mg

n = 421

n = 176

n = 377

n = 176

ESS = 209

n = 176

Placebo

n = 211

n = 177

n = 184

n = 177

ESS = 89

n = 177

0 0.5

1.0

1.5

2.0

*Bold indicates statistical significance. Values < 1 indicate a lower risk for acoramidis versus tafamidis 80 mg.

Placebo used as common anchor

Acoramidis (ATTRibute-CM) - Adjusted Placebo (ATTRibute-CM) - Adjusted Tafamidis 80 mg (ATTR-ACT) Placebo (ATTR-ACT)

1.0

0.9

IPD

Aggregate data

IPD

Aggregate data

Survival Probability

0.8

ClinicalTrial.gov identifier

ATTRibute-CM: Index Trial

ATTR-ACT: Comparator Trial

NCT03860935

NCT01994889

Study design

Phase 3, randomized, double-blind, placebo-controlled

Study period

April 2019 through May 2023

December 2013 through February 2018

Randomization

2:1 to acoramidis HCl 800 mg or matching placebo

1:1 to tafamidis 80 mgaor matching placebo

Study duration

30 months

Key eligibility criteria

Age, years

18-90

6MWD,bm

≥ 150

> 100

NT-proBNP,bpg/mL

≥ 300 to < 8500

≥ 600

eGFR,bmL/min/1.73 m2

≥ 15c

≥ 25

Primary efficacy endpoint

Composite of ACM, CVH, change from baseline in NT-proBNP level, and change from baseline in 6MWD

Hierarchical assessment of ACM and CVH

ITT population

Acoramidis, n = 421 Placebo, n = 211

Tafamidis 80 mg,an = 176 Placebo, n = 177

Unadjusted Placebo Arms

IPD

Survival

Aggregated

Time

Adjusted Placebo Arms

Placebo Anchor

Comparing anchored arms

(i.e. placebo) from different studies before and after adjustment is used to demonstrate that balance is achieved between populations after matching

Survival

Time

0.7

IPD

Aggregated

0.6

0.5

0.4

Base-case MAIC analysis

Acoramidis ESS

Placebo ESS

Acoramidis vs Tafamidis 80 mg

CVH RRR (95% CI)

ACM HR (95% CI)

209

0.663 (0.463-0.948)

0.719 (0.409-1.264)

+ RAS

186

0.695 (0.480-1.005)

0.762 (0.422-1.377)

+ Diuretics

147

0.631 (0.419-0.950)

0.652 (0.351-1.211)

+ RAS

+ Diuretics

137

0.634 (0.417-0.965)

0.690 (0.366-1.302)

+ RAS

+ Diuretics

+ Beta blockers

+ Antithrombotic agents

0.653 (0.387-1.104)

0.773 (0.366-1.634)

Without censoring for concomitant tafamidis

209

0.696 (0.494-0.981)

0.681 (0.395-1.174)

0 3 6 9 12 15 18 21 24 27 30 33

Time (Months)

aTafamidis 80 mg is the approved dose. The study also included an arm with tafamidis 20 mg, which was matched to placebo 1:2. bAt screening.

cStudy enrolment criteria cut-off. The primary analysis for efficacy was conducted in participants with eGFR ≥ 30 L/min/1.73 m2.

The figure uses colour to indicate inclusion status relative to aligned inclusion/exclusion criteria and icon size to reflect weighting. Blue represents participants aligned with ATTR-ACT inclusion/exclusion criteria and included in the anchored comparison. 'X' denotes ATTRibute-CM participants who were excluded during matching. In the MAIC-weighted populations panel, icon size reflects analytic weight, and the total contribution of the weighted population corresponds to the ESS. The curves in the schematic illustrate the concept of placebo anchoring and do not represent actual data from the trials.

Participants Remaining at Risk (Cumulative Events)

CORRESPONDING AND PRESENTING AUTHOR: Emer Joyce, [email protected]

REFERENCES: 1. Ruberg FL, et al. JAMA. 2024;331(9):778-791. 2. Lane T, et al. Circulation. 2019;140(1):16-26. 3. BridgeBio Pharma, Inc. Prescribing Information, Attruby (acoramidis). FDA, 2024. Accessed 27 February 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216540s000lbl.pdf.

4. Pfizer, Inc. Prescribing Information, Vyndaqel/Vyndamax (tafamidis). FDA, 2019. Accessed 27 February 2026. https://www.accessdata.fda.gov/drugsatfda_docs/ label/2019/211996s000,212161s000lbl.pdf. 5. Bayer, AG. Summary of Product Characteristics, Beyonttra (acoramidis). EMA, 2025. Accessed 27 February 2026. https://www.ema.europa.eu/en/documents/product-information/beyonttra-epar-product-information_en.pdf. 6. Pfizer Europe. Summary of Product

Characteristics Vyndaqel (tafamidis). EMA, 2016. Accessed 27 February 2026. https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar-product-information_en.pdf. 7. Bayer (Switzerland) AG. Approval summary, Beyonttra (acoramidis). Swissmedic, 2025. Accessed 24 February 2026. https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/authorisations/new-medicines/beyonttra-filmtabletten-acoramidisum.html.

8. Gillmore JD, et al. N Engl J Med. 2024;390(2):132-142. 9. Judge DP, et al. J Am Coll Cardiol. 2025;85(10):1003-1014. 10. Maurer MS, et al. N Engl J Med.

2018;379(11):1007-1016. 11. Fontana M, et al. Circ Heart Fail. 2025;18(8):e012112. 12. Ioannou A, et al. Circulation. 2022;146(22):1657-1670.

13. Tanaka S, et al. Value Health. 2024;27(9):1179-1190.

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; CVH, cardiovascular-related hospitalization; eGFR, estimated glomerular filtration rate; EM, effect modifier; ESS, effective sample size; HR, hazard ratio;

IPD, individual participant data; ITT, intention-to-treat; MAIC, matching-adjusted indirect comparison; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; RAS, renin-angiotensin system-acting agent; RRR, relative risk ratio; SD, standard deviation; TTR, transthyretin.

ACKNOWLEDGEMENTS: Under the direction of the authors, medical writing assistance was provided by Anja Becher, PhD, of Oxford PharmaGenesis and was funded by BridgeBio Pharma, Inc. Editorial support and critical review were provided by Jocelyn Hybiske, PhD, 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.