**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Daniel P. Judge
Medical University of South Carolina
Charleston, SC

**Main Body of the Abstract**
Background: Acoramidis is a next-generation, oral, near-complete stabilizer of transthyretin (TTR) under development for transthyretin amyloid cardiomyopathy (ATTR-CM). The ATTRibute-CM study demonstrated robust clinical efficacy assessed by a 4-component hierarchical analysis including all-cause mortality (ACM) and cardiovascular hospitalization (CVH). Here we report a prespecified survival analysis of the composite endpoint of ACM and CVH.
Methods: In contrast to the Finkelstein-Schoenfeld (F-S) hierarchical method, the analysis here uses the more traditional Kaplan-Meier (KM) Time-to-First Event approach based on the composite endpoint of ACM and CVH. Of the 632 subjects randomized, 611 were included in the modified intent-to-treat efficacy analysis of this 30-month study. Analyses of combined ACM/CVH according to F-S method and Kaplan-Meier Time-to-First Event Analysis (Cox proportional hazards model) were performed.
Results: The composite of Time-to-First-Event ACM or CVH was reported in 147 (35.9%) and 102 (50.5%) of acoramidis and placebo-treated subjects, respectively, corresponding to a 14.6% absolute risk reduction, and a hazard ratio of 0.645 (p=0.0008), as shown in the figure. The 2-component (ACM/CVH) F-S method was significant (p=0.0182), with a win ratio of 1.5 (95% CI: 1.1-2.0).
Conclusions: The KM survival analysis of Time-to-First Event for ACM or CVH reinforces the conclusion that acoramidis improves these key clinical outcomes in ATTR-CM patients as previously shown based on the 4-component primary endpoint using the F-S hierarchical analysis.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Daniel P. Judge
Medical University of South Carolina
Charleston, SC

**Main Body of the Abstract**
**Background:** Acoramidis is a next-generation, oral, near-complete stabilizer of transthyretin (TTR) under development for transthyretin amyloid cardiomyopathy (ATTR-CM). The ATTRibute-CM study demonstrated robust clinical efficacy assessed by a 4-component hierarchical analysis including all-cause mortality (ACM) and cardiovascular hospitalization (CVH). Here we report a prespecified survival analysis of the composite endpoint of ACM and CVH.
**Methods:** In contrast to the Finkelstein-Schoenfeld (F-S) hierarchical method, the analysis here uses the more traditional Kaplan-Meier (KM) Time-to-First Event approach based on the composite endpoint of ACM and CVH. Of the 632 subjects randomized, 611 were included in the modified intent-to-treat efficacy analysis of this 30-month study. Analyses of combined ACM/CVH according to F-S method and Kaplan-Meier Time-to-First Event Analysis (Cox proportional hazards model) were performed.
**Results:** The composite of Time-to-First-Event ACM or CVH was reported in 147 (35.9%) and 102 (50.5%) of acoramidis and placebo-treated subjects, respectively, corresponding to a 14.6% absolute risk reduction, and a hazard ratio of 0.645 (p=0.0008), as shown in the figure. The 2-component (ACM/CVH) F-S method was significant (p=0.0182), with a win ratio of 1.5 (95% CI: 1.1-2.0).
**Conclusions:** The KM survival analysis of Time-to-First Event for ACM or CVH reinforces the conclusion that acoramidis improves these key clinical outcomes in ATTR-CM patients as previously shown based on the 4-component primary endpoint using the F-S hierarchical analysis.



Acoramidis Improves Clinical Outcomes in Transthyretin Amyloid Cardiomyopathy PC132 (#349)

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.