Acoramidis, ATTR-CM, & Tafamidis: ATTRibute-CM Insights, with Daniel Judge, MD

Data from an analysis of the pivotal ATTRibute-CM trial offer further insight into the effects of acoramidis (Attruby) on outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).

Approved by the US Food and Drug Administration for ATTR-CM in November 2024, the latest info presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions demonstrate the benefits of acoramidis on the trial’s efficacy endpoint were consistent regardless of concomitant tafamidis (Vyndamax) use.1,2

“One of the questions that came up about the clinical trial is: did tafamidis play a role in in our endpoints? One of the things I was glad to show was that when we analyzed by 2 different methods to exclude patients with tafamidis… In both of those statistical analyzes that were prespecified, we showed that the effect of acoramidis was completely independent of tafamidis,” explained lead investigator Daniel Judge, MD, the Edwin W. and Teresa H. Rogers Endowed Chair for Cardiovascular Research at the Medical University of South Carolina, in an interview with HCPLive.

In the ATTRibute-CM trial, the investigational transthyretin stabilizer acoramidis met its 4-part primary efficacy endpoint, which included all-cause mortality, cardiovascular-related hospitalization, change in NT-proBNP, and 6-minute walk distance compared to placebo (P <.0001). As the trial permitted concomitant use of tafamidis (TAF), a pre-specified analysis was conducted to evaluate its potential impact on the primary efficacy endpoint.1,2

The ACC.25 analysis included 611 participants assessed at Month 30 using the Finkelstein-Schoenfeld (F-S) test. Investigators performed a pair of sensitivity analyses: the first excluded patients who received tafamidis and another disregarding observations after tafamidis initiation.1

Initial analysis indicated a lower proportion of patients in the acoramidis group (14.9%) received concurrent tafamidis compared to the placebo group (22.8%) and median tafamidis exposure was similar between groups, (11.6 and 10.5 months for acoramidis and placebo, respectively). Further analysis suggested the primary efficacy endpoint remained highly statistically significant in both sensitivity analyses (P <.0001 for both). Safety data detailed a consistent safety profile regardless of concurrent tafamidis use.1

For more on this study and the evolving landscape of ATTR-CM management, check out our interview with Judge from ACC.25:

Relevant disclosures for Judge include ADRx, Alleviant Medical, Astra Zeneca, BridgeBio, Capricor, Cytokinetics, Pfizer, Novo Nordisk, Tenaya Therapeutics, and others.

References:

1. Judge DP, Obi L, Mitter SS, et al. PRIMARY ENDPOINT EFFICACY RESULTS IN THE ATTRIBUTE-CM STUDY: PRE-SPECIFIED SENSITIVITY ANALYSES ADDRESSED TAFAMIDIS USE. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

2. BridgeBio. AttrubyTM (acoramidis), a Near Complete TTR Stabilizer (≥90%), approved by FDA to Reduce Cardiovascular Death and Cardiovascular-related Hospitalization in ATTR-CM Patients - BridgeBio. BridgeBio. Published November 23, 2024. Accessed April 1, 2025. https://bridgebio.com/news/attruby-acoramidis-a-near-complete-ttr-stabilizer-%E2%89%A590-approved-by-fda-to-reduce-cardiovascular-death-and-cardiovascular-related-hospitalization-in-attr-cm-patients/.