Impact of acoramidis on clinical stability in transthyretin amyloid cardiomyopathy: observations from ATTRibute-CM

AIMS: Acoramidis is an oral transthyretin (TTR) stabilizer that achieves near-complete (≥90%) TTR stabilization. This post-hoc analysis evaluated response categories based on NT-proBNP concentration and 6-minute walk distance (6MWD) changes among participants with transthyretin amyloid cardiomyopathy (ATTR-CM) in the phase 3 ATTRibute-CM trial. METHODS AND RESULTS: Clinically meaningful improvement (CMI) was defined as a decrease from baseline to Month 30 in NT-proBNP of >700 ng/L and >30%, and separately, a 6MWD increase of >35 m. Data from 611 participants were analysed (409: acoramidis; 202: placebo). Median baseline NT-proBNP and 6MWD values were 2273 ng/L and 365 m in the acoramidis group and 2274 ng/L and 352 m in the placebo group, respectively. A significantly higher proportion of participants in the acoramidis group reached CMI in NT-proBNP or 6MWD (22.7%) compared with the placebo group (8.9%; OR 3.0, 95% CI 1.8-5.1; p < 0.001). CONCLUSION: Acoramidis led to CMI from baseline in NT-proBNP concentration or 6MWD in a considerable proportion of participants with ATTR-CM. These findings suggest that the treatment paradigm of ATTR-CM may evolve from slowing disease progression to achieving improvement.