Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial
Daniel P. JudgeJulian D. GillmoreKevin AlexanderAmrut V. AmbardekarFrancesco CappelliMarianna FontanaPablo García‐PavíaJustin L. GrodinMartha GroganAhmad MasriJosé Nativi-NicolauLaura ObiciSteen Hvitfeldt PoulsenNitasha SarswatKeyur ShahPrem SomanTed LystigXiaofan CaoKevin WangM. PecoraroJean‐François TambyLeonid KatzUma SinhaJonathan C. FoxMathew S. Maurer
Key result
Continuous acoramidis cuts all-cause mortality ~36% vs. delayed initiation through 42 months.
- HR 0.64
- 95% CI 0.47-0.88
Why the study?
Does early and continuous use of acoramidis improve clinical outcomes in patients with transthyretin amyloid cardiomyopathy compared to delayed initiation?
Study Design
Type
RCT
Blinding
Open-label
Structured PICO
Does early and continuous use of acoramidis improve clinical outcomes in patients with transthyretin amyloid cardiomyopathy compared to delayed initiation?
P
Population
Participants with transthyretin amyloid cardiomyopathy who completed the ATTRibute-CM trial, followed through month 42.
I
Intervention
Continuous acoramidis (received acoramidis through month 30 in ATTRibute-CM and continued in the open-label extension).
C
Comparator
Placebo to acoramidis (received placebo through month 30 in ATTRibute-CM and switched to acoramidis in the open-label extension).
O
Outcome
Time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) through month 42.composite
Main Result
Hazard Ratio: 0.64 (95% CI 0.47–0.88)
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Continuous acoramidis efficacy data up to 42 months now underscore the importance, and this is true of all therapies, of early diagnosis and prompt initiation of treatment to improve outcomes in ATTR-CM.”
“Having a new first-line treatment option which provides excellent TTR stabilization and improves outcomes in this disease gives patients more options. Encouraging data suggest Attruby reduces all-cause mortality and cardiovascular hospitalization as early as 3 months after initiation of therapy. With continued advances in therapy, this previously fatal disease is becoming a manageable chronic cardiovascular condition.”
Implication
Early and continuous use of acoramidis in ATTR-CM provides sustained clinical benefits, including reduced mortality and cardiovascular hospitalizations, compared to delayed initiation.
Abstract
BACKGROUND: In the phase 3 randomized controlled study ATTRibute-CM (Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy), acoramidis, a transthyretin stabilizer, demonstrated significant efficacy on the primary end point. Participants with transthyretin amyloid cardiomyopathy who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report the efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE. METHODS: Participants who previously received acoramidis through month 30 in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through month 30 were switched to acoramidis (placebo to acoramidis). Participants who received concomitant tafamidis in ATTRibute-CM were required to discontinue it to be eligible to enroll in the OLE. Clinical efficacy outcomes analyzed through month 42 included time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH), ACM alone, first CVH alone, ACM or recurrent CVH, change from baseline in NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, serum transthyretin, and Kansas City Cardiomyopathy Questionnaire Overall Summary score. Safety outcomes were analyzed through month 42. Similar analyses were performed on ACM alone and first CVH alone, with hazard ratios of 0.64 (95% CI, 0.47-0.88) and 0.53 (95% CI, 0.41-0.69), respectively, at month 42. Treatment effects for NT-proBNP and 6-minute walk distance also favored continuous acoramidis. On initiation of open-label acoramidis in the placebo-to-acoramidis arm, there was a prompt increase in serum transthyretin. Quality of life assessed by Kansas City Cardiomyopathy Questionnaire Overall Summary score was well preserved in continuous-acoramidis participants compared with the placebo-to-acoramidis participants. No new clinically important safety issues were identified in this long-term evaluation. CONCLUSIONS: Early initiation and continuous use of acoramidis in the ATTRibute-CM study through month 42 of the ongoing OLE study were associated with sustained clinical benefits in a contemporary transthyretin amyloid cardiomyopathy cohort, with no clinically important safety issues newly identified. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04988386.
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Cite This Study
Judge et al. (2024) conducted an RCT in transthyretin amyloid cardiomyopathy. Acoramidis vs. Placebo switched to acoramidis was evaluated on all-cause mortality (ACM) alone (HR 0.64, 95% CI 0.47-0.88). Continuous use of acoramidis through month 42 reduced all-cause mortality (HR 0.64; 95% CI 0.47-0.88) and first cardiovascular hospitalization (HR 0.53; 95% CI 0.41-0.69) vs delayed initiation.