**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.**
Pablo Garcia-Pavia
Hospital Universitario Puerta de Hierro Majadahonda
Madrid, Spain

**Main Body of the Abstract**
Background: Two outcomes trials demonstrate efficacy and safety of transthyretin protein (TTR) stabilizers in patients with established ATTR-CM. Acoramidis mimics the stabilizing effects of the T119M TTR variant, which is known to be protective in patients harboring the pathogenic V30M variant. Asymptomatic carriers of a pathogenic TTR variant represent a group in whom ATTR amyloidosis may be subclinical but risk for disease development is high. Trends in surveillance of asymptomatic TTR variant carriers suggest that individuals at higher risk for incident near-term disease can be identified. The ACT-EARLY trial aims to test the hypothesis that prophylactic treatment with next-generation TTR stabilizer acoramidis can prevent or delay development of ATTR amyloidosis in asymptomatic pathogenic TTR variant carriers.
Methods: ACT-EARLY is a prospective, multinational, randomized, double-blind, placebo-controlled study evaluating treatment with acoramidis in asymptomatic carriers of a pathogenic TTR variant. Eligible participants are aged 18-75 years with a known pathogenic TTR variant who are within 10 years of predicted age of disease onset for their specific variant. Approximately 500 participants will be randomized 1:1 to receive acoramidis or placebo for up to 5 years (Figure). Primary efficacy endpoint is time to development of ATTR amyloidosis (cardiomyopathy and/or polyneuropathy). Additional endpoints include safety and tolerability of acoramidis and its effects on cardiac imaging parameters, plasma TTR concentration, nerve conduction, and neurofilament light chain.
Results: See Figure: ACT-EARLY Study Schematic.
Conclusion: ACT-EARLY is the first phase 3 trial to evaluate prophylactic therapy for the prevention of ATTR amyloidosis. Enrollment will begin in 2024.



**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.**
Pablo Garcia-Pavia
Hospital Universitario Puerta de Hierro Majadahonda
Madrid, Spain

**Main Body of the Abstract**
**Background**: Two outcomes trials demonstrate efficacy and safety of transthyretin protein (TTR) stabilizers in patients with established ATTR-CM. Acoramidis mimics the stabilizing effects of the T119M TTR variant, which is known to be protective in patients harboring the pathogenic V30M variant. Asymptomatic carriers of a pathogenic TTR variant represent a group in whom ATTR amyloidosis may be subclinical but risk for disease development is high. Trends in surveillance of asymptomatic TTR variant carriers suggest that individuals at higher risk for incident near-term disease can be identified. The ACT-EARLY trial aims to test the hypothesis that prophylactic treatment with next-generation TTR stabilizer acoramidis can prevent or delay development of ATTR amyloidosis in asymptomatic pathogenic TTR variant carriers.
**Methods**: ACT-EARLY is a prospective, multinational, randomized, double-blind, placebo-controlled study evaluating treatment with acoramidis in asymptomatic carriers of a pathogenic TTR variant. Eligible participants are aged 18-75 years with a known pathogenic TTR variant who are within 10 years of predicted age of disease onset for their specific variant. Approximately 500 participants will be randomized 1:1 to receive acoramidis or placebo for up to 5 years (Figure). Primary efficacy endpoint is time to development of ATTR amyloidosis (cardiomyopathy and/or polyneuropathy). Additional endpoints include safety and tolerability of acoramidis and its effects on cardiac imaging parameters, plasma TTR concentration, nerve conduction, and neurofilament light chain.
**Results**: See Figure: ACT-EARLY Study Schematic.
**Conclusion**: ACT-EARLY is the first phase 3 trial to evaluate prophylactic therapy for the prevention of ATTR amyloidosis. Enrollment will begin in 2024.



Rationale and Design of ACT-EARLY, the Acoramidis Transthyretin Amyloidosis Prevention Trial PC110 (#190)

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.