ATTRibute-CM: acoramidis (AG10) in patients with transthyretin amyloid cardiomyopathy

Presented at the ESC Congress 2023 by: Julian Gillmore, MD, PhD - London, UK

Introduction and methods

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of HF. This progressive and fatal disease is characterized by the deposit of TTR amyloid, which consists of misfolded TTR aggregates, in the heart. A potential therapeutic agent is acoramidis, a highly selective, potent, oral stabilizer of the TTR protein.

The ATTRibute-CM trial was an international, double-blind, placebo-controlled, phase 3 RCT in which 632 patients with symptomatic ATTR-CM (wild-type or variant) and NYHA class I–III HF symptoms were randomized in a 2:1 ratio to oral acoramidis 800 mg twice daily or placebo for 30 months. Patients who completed the 30-month ATTRibute-CM study could participate in an open-label extension study of acoramidis.

The primary endpoint was determined through a hierarchical analysis using the Finkelstein-Schoenfeld method of all-cause mortality, CV hospitalizations, change from baseline in NT-proBNP level (reflecting HF severity), and change from baseline in 6-minute walk distance (reflecting effort tolerance), all at 30 months. Secondary endpoints included the components of the primary endpoint, the Kansas City Cardiomyopathy Questionnaire Overall Summary score (reflecting quality of life), and serum TTR levels.

Main results

• The hierarchical primary endpoint analysis showed a win ratio in favor of acoramidis of 1.772 (95%CI: 1.417–2.217; P<0.0001), with 58% of the win ratio ties broken by all-cause mortality and CV hospitalizations.
• The results were consistent across subgroups, such as ATTR-CM genotype, NT-proBNP level, and age.
• Positive treatment effects were also seen for the secondary endpoints, with a better preservation of effort tolerance and quality of life and a reduced progressive rise in NT-proBNP level.
• The frequency of adverse events was balanced between both study arms, and the rate of serious adverse events favored acoramidis.

Conclusion

In ATTR-CM patients, treatment with acoramidis had a beneficial effect on the hierarchical composite outcome of all-cause mortality, CV hospitalizations, change in HF severity, or change in effort tolerance compared with placebo. Overall, acoramidis was safe and well tolerated.

- Our reporting is based on the information provided at the ESC Congress -