Acoramidis improves survival and functional status in ATTR-CM

Acoramidis demonstrated clinical and functional benefits over placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the ATTRibute-CM trial. The agent was well tolerated and survival rates in patients on acoramidis approached age-matched survival rates of individuals without ATTR-CM.

Acoramidis is an investigational, orally administered agent that aims to stabilise tetrameric transthyretin. The phase 3 ATTRIbute-CM study (NCT03860935) randomised 631 participants with ATRR-CM (median age 78 years; 10% women; 10% variant TTR carriers) 2:1 to 800 mg twice-daily acoramidis or placebo [1]. Tafamidis use was allowed after 12 months and the primary endpoint was a hierarchical analysis of all-cause mortality, cumulative frequency of cardiovascular hospitalisations, change from baseline NT-proBNP, and change from baseline in 6-minute walking distance (6MWD). Prof. Julian Gillmore (University College London, UK) presented the findings.

At 30 months, the win ratio was 1.77 (95% CI 1.42–2.22; P<0.0001; see Figure) in favour of the acoramidis group, meeting the primary endpoint. In addition, participants on acoramidis saw a relative risk reduction (RRR) in all-cause mortality of 25%. For cardiovascular mortality, the RRR was even higher, at 30%. Furthermore, the relative risk for cardiovascular hospitalisation in the acoramidis arm was 0.50 compared with the placebo arm (95% CI 0.36-0.70; P<0.0001). There were significant differences in the other individual components of the primary endpoint as well, namely the change in NT-proBNP (ratio of adjusted geometric mean fold-change 0.53; 95% CI 0.463–0.604; P<0.0001) and change in 6MWD (least squares mean difference of 39.64 m in favour of acoramidis; 95% CI 21.07–58.22; P<0.0001).

Figure: Primary outcome overall and by subgroups [1]



The rates of treatment-emergent adverse events (TEAEs) were comparable for the acoramidis group (98.1%) and the placebo group (97.6%). Serious TEAEs appeared to be somewhat more frequent in the placebo arm (54.6% vs 64.9%).

Prof. Gillmore concluded that the ATTRibute-CM trial showed that acoramidis was safe and efficacious in patients with ATTR-CM, delivering survival and functional benefits for this population.

1. 
   
   1. Gillmore JD, et al. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy: results of the ATTRibute-CM trial. Hot Line Session 5, ESC Congress 2023, 25–28 August, Amsterdam, the Netherlands.

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Posted on 30 October 202327 March 2024