Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: Acoramidis (ACOR), an investigational drug for ATTR-CM, achieves near-complete (≥90%) TTR stabilization at the dose under development. The Phase 3 ATTRibute-CM trial of ACOR vs placebo (PBO) met its primary hierarchical endpoint of ACM, CVH, change in NT-proBNP, and change in 6-minute walk distance at month (M) 30 (p<0.0001).
We report clinical outcomes following 36 and 42 months of treatment from the ongoing OLE.
Study Design and Methods: Participants who completed ATTRibute-CM were invited to enroll in the OLE. All OLE participants receive 800mg ACOR HCl BID.
Sample Size and Population Studied: Participants in the ATTRibute-CM OLE.
Intervention(s): 800 mg ACORAMIDIS (ACOR) HCl BID.
Power Calculations: Time-to-first event analyses using the Cox proportional hazards model were conducted at M36 and M42 for ACM, the composite of ACM or first CVH, and first CVH, and an Andersen-Gill (AG) analysis of instances of ACM and CVH as recurrent events was conducted at M36 and M42.
Primary Endpoint: Safety.
Secondary Endpoints: ACM, CVH.
Outcomes: Compared to those previously treated with placebo (PBO), for those who received ACOR through M36 and M42, respectively, the risk of ACM was significantly reduced by 35.7% (hazard ratio [HR], 95% CI: 0.64, 0.46-0.64; p=0.009) and 33.7% (HR, 95% CI: 0.64, 0.47-0.88; p=0.006; Fig. 1A), composite ACM/first CVH by 34.3% (HR, 95% CI: 0.59, 0.46-0.75; p<0.0001) and 33.9% (HR, 95% CI: 0.57, 0.46-0.57; p<0.0001; Fig. 1B), and first CVH by 40.5% (HR, 95% CI: 0.56, 0.42-0.73; p<0.0001) and 41.0% (HR, 95% CI: 0.53, 0.41-0.69; p<0.0001; Fig. 1C). By an AG analysis at M36 and M42, respectively, ACM and recurrent CVH were reduced by 34% (HR, 95% CI: 0.66, 0.56-0.79) and 39% (HR, 95% CI: 0.61, 0.52, 0.72, both p<0.0001). Treatment effects of ACOR in the prior PBO arm demonstrate a trend of improved survival (Figure 1A, extrapolated vs observed curves from M30). The overall safety profile of ACOR remains consistent with the parent study. ACOR has statistically significant long-term benefits on ACM, ACM or first CVH, and first CVH at both M36 and M42 of the ongoing OLE, consistent with the ATTRibute-CM study.