Rationale and Design of ACO-REAL: A Real-World Non-Interventional Study of Acoramidis in Routine Clinical Practice

Abstract

Acoramidis, an oral transthyretin stabilizer that achieves near-complete stabilization, is approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on the phase 3 study, ATTRibute-CM (NCT03860935). To complement trial data, ACO-REAL (NCT07235462) was designed to generate real-world evidence on acoramidis use in ATTR-CM. This article describes the rationale and design of ACO-REAL. ACO-REAL is an ongoing, prospective, non-interventional, multicenter study planned in approximately 2000 adults with ATTR-CM (wild-type or variant) initiating treatment with acoramidis in real-world settings across 21 European countries. The primary objective of ACO-REAL is to assess the characteristics and treatment patterns of participants with ATTR-CM receiving acoramidis during an observational period of around 12 months. The primary objective is to assess demographics (including age and sex), disease characteristics, and treatment patterns of participants treated with acoramidis. Disease characteristics include type, diagnosis, and manifestations of ATTR-CM, and ATTR-CM-relevant comorbidities. Treatment patterns include adherence, persistence, and reasons for treatment modifications, including switching from a different ATTR-CM medication to acoramidis. The secondary objective is to describe the safety profile of acoramidis. The clinical course of ATTR-CM in participants initiating acoramidis is also being evaluated through measuring cardiac function, functional capacity and health status (New York Heart Association classification and 6-min walk distance), and health-related quality of life (Kansas City Cardiomyopathy Questionnaire and EuroQol 5-Dimension 5-Level questionnaire). Healthcare resource utilization is also being evaluated. Statistical analyses will be exploratory and descriptive. Categorical variables will be presented as frequencies and continuous variables as sample statistics. ACO-REAL is the first multinational observational study to collect regular, prospective, real-world data in participants with ATTR-CM treated with acoramidis. This study aims to provide insights into ATTR-CM treatment using real-world evidence from European healthcare systems and may help to guide decision-making in clinical practice. Graphical abstract available for this article. ClinicalTrials.gov identifier, NCT07235462 Acoramidis is an oral drug that was approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), a type of heart disease, based on positive results from the ATTRibute-CM study (NCT03860935). This manuscript describes a new study, ACO-REAL (NCT07235462), that aims to provide information about acoramidis in patients in the real world. ACO-REAL is an ongoing study that is collecting data from participants over the course of 12 months who are receiving acoramidis to treat ATTR-CM. The study will include around 2000 participants from 21 European countries, and will focus on participant characteristics, treatments, reasons for any changes in treatment, and side effects. The study will assess participants’ heart function, how the ATTR-CM disease changes over time, as well as participants’ overall health and ability to function normally. The study will also assess quality of life and use of healthcare resources (such as hospital and emergency room visits). By analyzing data in a broad European population, this study should improve understanding of acoramidis use in patients with ATTR-CM in the real world, adding to data obtained from controlled clinical trials.