**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.**
Mathew S. Maurer
Columbia University
New York, NY

**Main Body of the Abstract**
Background: Acoramidis is a novel, high-affinity stabilizer that achieves ≥90% transthyretin (TTR) stabilization. The phase 3 study, ATTRibute-CM, met its primary hierarchical efficacy endpoint with mortality, morbidity, and function components (p<0.0001). Acoramidis treatment resulted in a 25% relative risk reduction (RRR) in all-cause mortality (ACM) and 30% RRR in cardiovascular mortality. We report results of acoramidis-mediated change in serum TTR, an in vivo measure of TTR stabilization, and its relationship to ACM.
Methods: Modeling and simulation analyses described acoramidis population pharmacokinetics. Exposure-response relationships were modeled for ACM versus serum TTR (prealbumin).
Results: Serum TTR levels on day 28 of dosing predicted survival in univariate analysis (Figure; p=0.00161). A Kaplan-Meier plot of overall survival stratified by quartile of serum TTR change at day 28 showed significant differences by the log-rank test (p=0.0055). In multivariate analysis, after adjusting for baseline demographic variables, diuretics, New York Heart Association functional classification, baseline serum TTR, TTR variant vs wild-type, and National Amyloidosis Centre stage, the change in serum TTR remained an independent predictor of ACM (p=0.02257).
Conclusion: Statistical modeling demonstrates that acoramidis-mediated increase in serum TTR at day 28 is an independent predictor of survival.



**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.**
Mathew S. Maurer
Columbia University
New York, NY

**Main Body of the Abstract**
**Background:** Acoramidis is a novel, high-affinity stabilizer that achieves ≥90% transthyretin (TTR) stabilization. The phase 3 study, ATTRibute-CM, met its primary hierarchical efficacy endpoint with mortality, morbidity, and function components (p<0.0001). Acoramidis treatment resulted in a 25% relative risk reduction (RRR) in all-cause mortality (ACM) and 30% RRR in cardiovascular mortality. We report results of acoramidis-mediated change in serum TTR, an in vivo measure of TTR stabilization, and its relationship to ACM.
**Methods:** Modeling and simulation analyses described acoramidis population pharmacokinetics. Exposure-response relationships were modeled for ACM versus serum TTR (prealbumin).
**Results:** Serum TTR levels on day 28 of dosing predicted survival in univariate analysis (Figure; p=0.00161). A Kaplan-Meier plot of overall survival stratified by quartile of serum TTR change at day 28 showed significant differences by the log-rank test (p=0.0055). In multivariate analysis, after adjusting for baseline demographic variables, diuretics, New York Heart Association functional classification, baseline serum TTR, TTR variant vs wild-type, and National Amyloidosis Centre stage, the change in serum TTR remained an independent predictor of ACM (p=0.02257).
**Conclusion:** Statistical modeling demonstrates that acoramidis-mediated increase in serum TTR at day 28 is an independent predictor of survival.



Early Increase in Serum Transthyretin Level is an Independent Predictor of Improved Survival in ATTR Cardiomyopathy: Insights From Acoramidis Phase 3 Study ATTRibute-CM PC130 (#321)

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.