Breaking Down Acoramidis OLE Data from HFSA 2023, with Ahmad Masri, MD, MS


Ahmad Masri, MD, MS, discusses long-term data from the open-label extension period of the phase 2 AG10-201 trial examining acoramidis in patients with ATTR-CM.

New long-term safety and tolerability data from a phase 2 trial examining acoramidis is providing clinicians additional insight into the effects of the next-generation TTR stabilizer in patients with symptomatic transthyretin amyloid cardiomyopathy (ATTR-CM).

Presented by Ahmad Masri, MD, director of the Cardiomyopathy Center at Oregon Health and Science University, at the Heart Failure Society of America (HFSA) 2023 Annual Scientific Meeting, results of the open-label extension period of the AG10-201 study provide an overview of the effects of acoramidis out to 4 years of treatment, with at least 53% of the enrolled population serving for a median of 4.6 years with acoramidis.1

“I think it’s important to always understand when you have a novel therapy the primary data that come out of the clinical trial have a purpose, but then if you want to understand how the drug works from a safety, and potential efficacy, standpoint using a surrogate endpoint over time you want to have long-term extension studies, and this is essentially what we have here,” explained Masri, in an interview with HCPLive Cardiology at HFSA 2023.

Published in 2019, the AG10-201 study was a randomized, double-blind, placebo-controlled study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of AG10 in ATTR-CM patients with symptomatic, chronic heart failure. The trial enrolled 49 patients and randomized them in a 1:1:1 ratio to AG10 400 mg, AG10 800 mg, or placebo twice daily for 28 days, with a primary endpoint of TTR stability assessed by changes in serum TTR.2

Results of the trial suggested treatment with acoramidis was well-tolerated, achieved target plasma concentrations and demonstrated near-complete stabilization of TTR. Investigators pointed out TTR stabilization was more complete and less variable at the higher dose with stabilization by fluorescent probe exclusion of 92% (Standard deviation [SD], 10%) at trough and 96% (SD, 9%) at peak (both p < 10-12 vs. placebo).2

At HFSA 2023, the open-label extension data presented by Masri included 47 patients from the original trial. The primary endpoint for the HFSA 2023 analysis of long-term data was the long-term safety and tolerability of acoramidis. Investigators also included multiple secondary endpoints related to pharmacokinetic and pharmacodynamic assessment of TTR stabilization.1

Among the 47 patients who entered the long-term open-label extension portion of the trial, 25 remained as of January 06, 2023. Among this cohort, the median time since phase 2 enrollment was 55 months. Investigators found acoramidis was generally well-tolerated and the observed adverse events were consistent with disease severity, concurrent illness, and/or age. Additional analysis revealed the median (25th, 75th percentiles) change from baseline to month 45 in NT-proBNP among this cohort was -11 (-643, 242) pg/mL.1

For more on the long-term follow-up data on acoramidis in ATTR-CM, check out our interview with Masri from the floor at HFSA 2023.

Masri reports having received funding for consulting or research grants from Cytokinetics, Lexicon, Pfizer, Ionis, Bristol Myers Squibb, and more.


  1. Masri A, Aras M, Falk RH, et al. Long-term Safety And Tolerability Of Acoramidis (AG10) In Symptomatic Transthyretin Amyloid Cardiomyopathy: 4-year Update From An Ongoing, Phase 2, Open-label Extension Study. Paper presented at: Heart Failure Society of America 2023 Annual Scientific Meeting; October 6 - 9; Cleveland, OH. Accessed October 9, 2023.
  2. Judge DP, Heitner SB, Falk RH, et al. Transthyretin Stabilization by AG10 in Symptomatic Transthyretin Amyloid Cardiomyopathy. J Am Coll Cardiol. 2019;74(3):285-295. doi:10.1016/j.jacc.2019.03.012
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