Acoramidis boosts clinical outcomes in ATTR-CM

Treatment with the investigational agent acoramidis significantly reduced all-cause mortality (ACM) and recurrent cardiovascular-related hospitalizations (CVH) at 30 months for patients with transthyretin amyloid cardiomyopathy (ATTR-CM), according to a post hoc analysis of the phase III ATTRibute-CM trial presented at HFSA 2024.

Based on the negative binomial regression and Andersen-Gill analyses, acoramidis significantly reduced the risk of the composite outcome of ACM and recurrent CVH by 42 percent (p=0.0005) and 30.5 percent (hazard ratio [HR], 0.695; p=0.0008), respectively, at month 30 compared with placebo. [Judge, et al, HFSA 2024]

Additionally, patients treated with acoramidis had lower rates of ACM (19.3 percent vs 25.7 percent) and CVH (26.7 percent vs 42.6 percent) than those treated with placebo, resulting in fewer patients having ACM or CVH by month 30 in the acoramidis arm (36 percent vs 51 percent).

Acoramidis is an investigational, next-generation, orally administered, high-affinity transthyretin (TTR) stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90-percent stabilization across the dosing interval as measured ex vivo. [N Engl J Med 2024;390:132-142]

“This post hoc analysis provides further evidence that near-complete TTR stabilization with acoramidis can improve clinical outcomes for patients with ATTR-CM. The reduction of hospitalizations and ACM seen in ATTRibute-CM heightens the case for acoramidis as a first-line therapy given its potential to improve the overall quality of life for patients,” said lead author Dr Daniel Judge from the Medical University of South Carolina, Charleston, South Carolina, US, in a press release.

The study included 611 patients (mean age 77 years) with ATTR-CM who were randomized 2:1 to receive either acoramidis (n=409) or placebo (n=202). All baseline characteristics were similar in both groups.

In terms of safety, the incidence of serious treatment-emergent adverse events (TEAEs) was lower in the acoramidis arm than in the placebo arm (54.6 percent vs 64.9 percent). However, more treatment-related AEs were observed with acoramidis (11.9 percent vs 5.2 percent).

“As previously reported, no safety signals of potential clinical concern were identified in the ATTRibute-CM,” Judge noted.

In light of the positive results of the ATTRibute-CM trial, a new drug application has been submitted to the US FDA. Decision is expected in 2025.