Acoramidis 356mg tablets

Abstract Background: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is the most common form of restrictive cardiomyopathy. Emerging pharmacological therapies aim to alter the natural history of disease and delay its advancement. However, data directly comparing the efficacy of different drug classes versus placebo remain limited. Objectives: This systematic review assessed the efficacy of TTR stabilizers and silencers compared with placebo on all-cause mortality, hospitalizations, functional outcomes, and serum levels of the biomarker NT-proBNP in patients with ATTR-CM. Methods: A comprehensive search of PubMed, Embase, and Cochrane databases was conducted for randomized controlled trials (RCTs) published through April 2025. Eligible studies compared patisiran, tafamidis, inotersen, revusiran, acoramidis, or vutrisiran to placebo in patients with ATTR-CM. Analyses were stratified by drug class, and statistical significance was set at p<0.05. Results: Seven RCTs involving 2,526 participants were included; 42.5% received TTR stabilizers and 57.5% received TTR silencers. Compared with placebo, TTR stabilizers significantly reduced all-cause mortality (RR: 0.71; 95% CI 0.59-0.87; p=0.0006) and hospitalizations (RR: 0.81; 95% CI 0.73-0.89; p<0,0001). TTR silencers did not significantly reduce mortality (RR: 0.79; 95% CI 0.37-1.68; p=0.54) or hospitalizations (RR: 1.11; 95% CI 0.83-1.48; p=0.48). Both therapies were associated with improvements in 6-minute walk distance, quality of life, and reductions in serum NT-proBNP levels. Conclusion: TTR stabilizers significantly reduced all-cause mortality and hospitalizations in patients with ATTR-CM compared with placebo. These benefits were not observed with TTR silencers, potentially due to shorter follow-up durations in the studies evaluated. Both therapies improved functional status and serum levels of NT-proBNP.

Abstract licence: CC BY

Abstract Aims Transthyretin cardiac amyloidosis (ATTR-CA) is an important cause of heart failure (HF). Several therapies demonstrated an efficacy in reducing hard and surrogate endpoints. We compared the relative efficacy of therapies evaluated in completed phase III trials. Methods and results We conducted a network meta-analysis using data from ATTR-ACT, ATTRIBUTE-CM, APOLLO-B, and HELIOS-B. The primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Secondary endpoints were changes in the 6-minute walk distance (6MWD) and Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) scores. For the primary endpoint, tafamidis and vutrisiran demonstrated a significant survival benefit over placebo; acoramidis approached significance. In indirect comparisons, there was no clear evidence of a larger absolute risk reduction for any drug. Tafamidis was associated with the lowest risk for the primary endpoint (surface under the cumulative ranking, SUCRA 82%), followed by vutrisiran monotherapy (70%). Regarding changes in 6MWD, tafamidis and acoramidis had the highest SUCRA curve values (97% and 69%, respectively). For KCCQ-OS changes, tafamidis also had the highest SUCRA (87%), followed by acoramidis (79%) and vutrisiran monotherapy (67%). When the ATTR-ACT trial was excluded from the analysis, vutrisiran monotherapy consistently showed the highest probability of being ranked better than other treatments in terms of primary end-point. Conclusion Although differences in trial design and study populations complicate direct efficacy comparisons, tafamidis demonstrated the highest efficacy in improving survival, reducing cardiovascular hospitalizations, and enhancing functional capacity and quality of life in patients with ATTR-CA, but also vutrisiran and acoramidis emerged as viable options.

Abstract licence: CC BY-NC 4.0

Plain Language SummaryWhat is this plain language review about?This plain language review describes the results of a study called ATTRibute-CM. This study looked at how well a drug called acoramidis worked to treat people with transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-CM is a type of heart disease that occurs when a protein called transthyretin (TTR) breaks down, changes shape (misfolds), and forms harmful amyloid fibrils (clumps of misfolded proteins). These amyloid fibrils then accumulate in the heart muscle, leading to thickening and stiffening of the heart walls, thereby reducing its ability to pump blood effectively. Symptoms of ATTR-CM include shortness of breath, swelling in the lower legs, and irregular heart beat.What is ATTRibute-CM?ATTRibute-CM is a study that recruited 632 participants with ATTR-CM who either took acoramidis HCl (the salt form of acoramidis) 800 mg or a placebo (a pill that looked like acoramidis, but did not contain any medicine) twice a day by mouth for 30 months.What were the results and what do they mean?Compared to participants in the placebo group, participants in the acoramidis group had better results on efficacy measures (measures of how well a treatment works) that included death due to any cause, being admitted to a hospital for a heart problem, change in NT-proBNP level (a type of protein that indicates worsening heart failure), and change in 6-minute walking distance. Common side effects included diarrhea and gout. Acoramidis showed clinical benefit in people with ATTR-CM compared with placebo.Clinical trial number: NCT03860935

Abstract licence: CC BY-NC-ND 4.0