Acoramidis Reduces Total Cardiovascular Events By Nearly 50% in ATTR-CM

Additional data from an exploratory analysis of the ATTRibute-CM trial suggests acoramidis (Attruby) treatment over 30 months significantly reduced the risk of cumulative cardiovascular events by 49%.

Presented by Ahmad Masri, MD, MS, director of the Knight Cardiovascular Institute Cardiac Amyloidosis Program at Oregon Health & Sciences University, during the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025, data from the trial further contextualize the potential benefit of acoradmis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).

“The association between early and robust (≥90%) TTR stabilization with acoramidis and the observed early reduction in CV event burden warrants further investigation,” wrote investigators.

An oral, twice-daily medication, acoramidis received approval from the US Food and Drug Administration in November 2024 for treatment of wild-type or variant ATTR-CM to reduce death and hospitalization related to heart problems based on data from the ATTRibute-CM trial. At the time of approval, acoramidis became the second agent to receive an indication for the condition. The other approved agent, tafamidis, is also a TTR protein stabilizer, though BridgeBio bills acoramidis as a next-generation TTR protein stabilizer.

The pivotal ATTRibute-CM study was a multicenter, international, randomized, double-blind, placebo-controlled study examining the safety and efficacy of acoramidis relative to placebo among 611 adult patients. The trial met its primary endpoint of all-cause mortality and cumulative frequency of cardiovascular-related hospitalizations over 30 months, with the acoramidis arm experiencing a 42% reduction relative to placebo at month 30. Patients who completed the trial were invited to take part in an open-label extension period, which could last up to 42 months total.

The HFSA 2025 study evaluated participants from the modified intention-to-treat population who received either continuous acoramidis or placebo for 30 months before entering the OLE. Baseline characteristics were well balanced between groups, with approximately 90% of the study population having wild-type ATTR-CM and 89.6% male.

At 30 months, results suggested treatment with acoramidis was associated with a 49% reduction in the cumulative risk of cardiovascular mortality or recurrent CV hospitalization versus placebo (Hazard Ratio [HR], 0.51; 95% Confidence Interval [CI], 0.43–0.62; P <.0001), with differences emerging as early as month 1.

This translated to 53 fewer cardiovascular events per 100 participants treated over the study period, reinforcing the importance of early therapy initiation in ATTR-CM (95% CI, 29–79). Recurrent cardiovascular hospitalizations alone was reduced by 50% over 30 months, demonstrating the drug’s ability to not just delay the first event but prevent subsequent ones (Relative Risk Reduction, 0.50; 95% CI, 0.35–0.69; P <.0001).

Investigators also highlighted continuous acoramidis use through the open-label extension period was associated with a 45% reduction in the risk of cardiovascular mortality at 42 months compared with participants who transitioned from placebo to acoramidis after month 30 (HR, 0.55; 95% CI, 0.39–0.79; P = .0011). According to investigators, this finding suggests a time-dependent benefit and supports the value of initiating therapy promptly upon diagnosis to maximize event reduction.

“These exploratory findings suggest that cumulative event burden may occur early, highlighting the importance of timely evaluation and diagnosis in ATTR-CM,” wrote investigators in the simultaneously published JACC manuscript.

References:
  1. Masri A. Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis from ATTRibute-CM. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.
  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 September 28, 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/

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