Kevin M. Alexander
Stanford University School of Medicine
Palo Alto, CA

Main Body of the Abstract
Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by inexorable disease progression resulting in substantial cardiovascular morbidity and mortality. Acoramidis – a novel, potent, near-complete transthyretin (TTR) oral stabilizer that increases serum TTR (aka prealbumin) – is under development for the treatment of ATTR-CM. The phase 3 ATTRibute-CM trial of acoramidis was a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of acoramidis in symptomatic ATTR-CM patients that met its primary hierarchical efficacy endpoint with mortality, morbidity, and function components (p<0.0001). The trial demonstrated improved clinical outcomes in ATTR-CM patients including a 50% reduction in the risk of cardiovascular hospitalizations (CVHs) compared to placebo over 30 months.
Methods: We report a prespecified time-to-first-event analysis for the composite of cardiovascular mortality (CVM) or CVH, based on adjudicated data, using the Cox Proportional Hazards model.
Results: In ATTRibute-CM, the mean (±SD) age of the patients was 77±6.6 years, 90.2% were men, and 90.3% had wild-type TTR. The composite of time to first event (CVM or CVH) was reported in 136/409 (33.3%) and 98/202 (48.5%) of acoramidis and placebo-treated patients, respectively, corresponding to a 15.2% absolute risk reduction, (number need to treat: 7), and a 38.2% hazard reduction (p=0.0003). As shown in the figure, the Kaplan-Meier curves separate early, at month 3, and steadily diverge through month 30.
Conclusion: Acoramidis treatment resulted in an early and profound reduction in the composite endpoint of cardiovascular death or hospitalization in ATTR-CM patients.

Kevin M. Alexander
Stanford University School of Medicine
Palo Alto, CA

**Main Body of the Abstract**
**Background**: Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by inexorable disease progression resulting in substantial cardiovascular morbidity and mortality. Acoramidis – a novel, potent, near-complete transthyretin (TTR) oral stabilizer that increases serum TTR (aka prealbumin) – is under development for the treatment of ATTR-CM. The phase 3 ATTRibute-CM trial of acoramidis was a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of acoramidis in symptomatic ATTR-CM patients that met its primary hierarchical efficacy endpoint with mortality, morbidity, and function components (p<0.0001). The trial demonstrated improved clinical outcomes in ATTR-CM patients including a 50% reduction in the risk of cardiovascular hospitalizations (CVHs) compared to placebo over 30 months.
**Methods**: We report a prespecified time-to-first-event analysis for the composite of cardiovascular mortality (CVM) or CVH, based on adjudicated data, using the Cox Proportional Hazards model.
**Results**: In ATTRibute-CM, the mean (±SD) age of the patients was 77±6.6 years, 90.2% were men, and 90.3% had wild-type TTR. The composite of time to first event (CVM or CVH) was reported in 136/409 (33.3%) and 98/202 (48.5%) of acoramidis and placebo-treated patients, respectively, corresponding to a 15.2% absolute risk reduction, (number need to treat: 7), and a 38.2% hazard reduction (p=0.0003). As shown in the figure, the Kaplan-Meier curves separate early, at month 3, and steadily diverge through month 30.
**Conclusion:** Acoramidis treatment resulted in an early and profound reduction in the composite endpoint of cardiovascular death or hospitalization in ATTR-CM patients.

Acoramidis Achieves Early Reduction in Cardiovascular Death or Hospitalization in Transthyretin Amyloid Cardiomyopathy (ATTR-CM): Results from the ATTRibute-CM Clinical Trial OC7 (#281)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.