Acoramidis improves health-related quality of life in wild-type and variant transthyretin amyloid cardiomyopathy: An EQ-5D-5L subgroup analysis from ATTRibute-CM

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, often fatal cardiomyopathy associated with declining health-related quality of life (HRQoL). It can occur due to an inherited mutation (variant, ATTRv-CM) or due to age (wild-type, ATTRwt-CM). The EQ-5D-5L is a patient-reported tool to evaluate HRQoL across dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and overall health state (EQ VAS). Acoramidis, an oral, approved therapy for ATTR-CM, achieves near-complete (≥90%) transthyretin stabilization. In the phase 3 ATTRibute-CM study (NCT03860935), acoramidis had a statistically significant and clinically meaningful benefit on the EQ-5D-5L index and EQ VAS scores vs placebo (least-squares mean [LSM] difference: 0.13 and 9.55, respectively; both p<0.0001). The differential effect of acoramidis on HRQoL in ATTRwt-CM and ATTRv-CM has not been established. Purpose To evaluate whether the effect of acoramidis on HRQoL differed between participants with ATTRwt-CM and ATTRv-CM. Methods Participants in ATTRibute-CM were randomized 2:1 to receive acoramidis HCl 800 mg or placebo twice daily for 30 months. Efficacy analyses were conducted in the modified intention-to-treat population. EQ-5D-5L index and EQ VAS scores (with higher scores equating to better health for both) were evaluated at baseline, 6, 9 and 12 months, and then every 6 months through Month 30. In this post hoc analysis, LSM changes from baseline to Month 30 in EQ-5D-5L index and EQ VAS scores were analysed using a mixed model for repeated measures in ATTRwt-CM and ATTRv-CM subgroups. The minimal clinically important difference in the index scores uses ranges from 0.037 to 0.069 for the EQ-5D-5L and from 6.5 to 8.2 for the EQ VAS. Results Of the 611 participants in the modified intention-to-treat population (acoramidis, n=409; placebo, n=202), 59 had ATTRv-CM (acoramidis, n=39; placebo, n=20) and 552 had ATTRwt-CM (acoramidis, n=370; placebo, n=182). At baseline, EQ-5D-5L and EQ VAS values were comparable across genotypes and treatment groups (Figures 1, 2). Consistent with the overall population, acoramidis significantly attenuated the decline in EQ-5D-5L index score from baseline to Month 30 vs placebo in participants with ATTRwt-CM (LSM difference: 0.11, p<0.0001) and ATTRv-CM (LSM difference: 0.24, p=0.005; Figure 1). This effect was also observed for EQ VAS score (ATTRwt-CM LSM difference: 8.65, p<0.0001; ATTRv-CM LSM difference: 17.38, p=0.0092; Figure 2). Differences vs placebo were numerically greater in participants with ATTRv-CM. Conclusions Treatment with acoramidis resulted in significant and clinically meaningful benefits in HRQoL in both ATTRwt-CM and ATTRv-CM. Greater impact on HRQoL vs placebo was observed in participants with ATTRv-CM.