Acoramidis Attenuates Decline in Heart Failure–Related Health Status in ATTR-CM

Acoramidis (Attruby; BridgeBio Pharma), an oral transthyretin (TTR) stabilizer approved for transthyretin amyloid cardiomyopathy (ATTR-CM), significantly slowed the decline in heart failure (HF)–related health status compared with placebo, according to a secondary analysis of the phase 3 ATTRibute-CM (NCT03860935) randomized clinical trial published online in JAMA Cardiology.¹

“In this secondary analysis of the ATTRibute-CM randomized clinical trial among patients with ATTR-CM, acoramidis attenuated the decline in patient-reported health status vs placebo, with sustained results that were consistent across prespecified subgroups,” wrote the researchers of the study.

ATTR-CM Drives Progressive Declines in Patient-Reported Health

ATTR-CM is a progressive, often fatal disease in which destabilized TTR tetramers misfold and deposit as amyloid fibrils in the myocardium, impairing cardiac function and driving progressive declines in patients' symptoms, function, and quality of life. Although acoramidis, which achieves near-complete (≥ 90%) TTR stabilization, was already known to reduce mortality and cardiovascular-related hospitalizations (CVH) in ATTRibute-CM, its effect on patient-reported health status had not been comprehensively described until now.^1,2

A Secondary Analysis of ATTRibute-CM Participants

Investigators evaluated 611 adults with symptomatic ATTR-CM in the modified intention-to-treat population, randomized 2:1 to oral acoramidis hydrochloride 800 mg twice daily or matching placebo for 30 months.¹ The prespecified secondary outcome was the least-squares mean (LSM) difference in the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS), a patient-reported measure of HF-related symptoms, function, and quality of life ranging from 0 to 100.

A 9.9-Point KCCQ-OS Gap Emerged Early and Widened Through Month 30

By month 30, the LSM change in KCCQ-OS from baseline was −11.5 with acoramidis vs −21.4 with placebo, an LSM difference of 9.9 points (95% CI, 6.0-13.9; P < .001) favoring acoramidis—a magnitude the authors characterize as a moderate clinically meaningful benefit. Differences between groups emerged within the first 3 months and became statistically significant after month 9.

Additionally, using integrated survival and health-status categories, 46.6% of acoramidis recipients were classified as "alive and not worse" (KCCQ-OS decrease of less than 5 points) at month 30 compared with 29.8% of placebo recipients (OR, 2.1; 95% CI, 1.4-3.1; P < .001; number needed to treat [NNT] = 6). Similarly, 45.8% of acoramidis recipients were "alive and well, per KCCQ-OS score greater than 60, with less than a 10-point decrease, vs 31.4% on placebo (OR, 1.9; 95% CI, 1.3-2.8; P < .001; NNT = 7), and 25.3% were "alive and better" who had more than a 5-point improvement vs 13.8% on placebo (OR, 2.1; 95% CI, 1.3-3.4; P = .002; NNT = 9). Benefits were consistent across prespecified subgroups, including TTR genotype, age, sex, and New York Heart Association class, with no evidence of heterogeneity in treatment effect.

The benefits extended across individual KCCQ domains as well. Acoramidis showed numerically greater preservation of physical limitation, social limitation, symptom burden, and quality of life scores relative to placebo, with the authors noting particularly pronounced differences in quality-of-life and self-efficacy domains. A prespecified sensitivity analysis excluding participants who received concomitant tafamidis after month 12 showed a similarly moderate and meaningful benefit favoring acoramidis alone (LSM difference, 9.7 points; 95% CI, 5.3-14.1; P < .001), suggesting the health status benefit was not driven by crossover treatment.

However, the researchers noted some limitations, including that ATTRibute-CM's eligibility criteria may limit generalizability; that KCCQ-OS assessments were added via protocol amendment, so not all participants had a month-3 reading; and that the trial enrolled relatively few women and patients with variant ATTR-CM, populations in which health-status trajectories may differ.

A Patient-Centered Case Amid a $18,759 Monthly Price Tag

The findings arrive as payers continue to refine utilization management for ATTR-CM therapies. Acoramidis carries a list price of $18,759 per month, and coverage typically requires documentation of a pathogenic TTR mutation or biopsy-confirmed amyloid deposits before initial authorization. ³ For managed care decision makers, a durable, patient-centered benefit, not just reduced mortality and hospitalization, may factor into value assessments and formulary discussions, particularly as it reinforces the rationale for earlier diagnosis and timely treatment initiation in a disease where the primary policy goal is preserving function and quality of life for as long as possible.¹

“These findings demonstrate that the survival and CVH benefits of acoramidis are accompanied by meaningful stabilization of patient-reported health status in ATTR-CM,” wrote the researchers.

References

1. Sherrod CF IV, Fontana M, Gillmore JD, et al. Effect of acoramidis on heart failure–related health status: a secondary analysis of the ATTRibute-CM randomized clinical trial. JAMA Cardiol. Publilshed online July 29 2026. doi:10.1001/jamacardio.2026.2413
2. Gillmore JD, Judge DP, Cappelli F, et al. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. N Engl J Med. 2024;390(2):132-142. doi:10.1056/NEJMoa2305434
3. FDA approves Attruby for heart failure indication. Managed Healthcare Executive.^® November 25, 2024. Accessed July 27, 2026. https://www.managedhealthcareexecutive.com/view/fda-approves-attruby-for-hearth-failure-indication