Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial.

Autor:	Judge DP; Division of Cardiology, Medical University of South Carolina, Charleston, SC., Gillmore JD; National Amyloidosis Centre, University College London, Royal Free Hospital, London, UK., Alexander KM; Division of Cardiovascular Medicine, Department of Medicine, Stanford Center for Clinical Research, Stanford University School of Medicine, Palo Alto, CA., Ambardekar AV; Department of Medicine, Division of Cardiology, Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO., Cappelli F; Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy., Fontana M; National Amyloidosis Centre, University College London, Royal Free Hospital, London, UK., García-Pavía P; Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Grodin JL; Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX., Grogan M; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN., Hanna M; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH., Masri A; Division of Cardiology, Oregon Health & Science University, Portland, OR., Nativi-Nicolau J; Department of Transplant, Mayo Clinic, Jacksonville, FL., Obici L; Amyloidosis Research and Treatment Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Hvitfeldt Poulsen S; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark, DENMARK., Sarswat N; Division of Cardiovascular Medicine, University of Chicago Medicine, Chicago, IL., Shah K; Pauley Heart Center, Department of Cardiology, Virginia Commonwealth University, Richmond, VA., Soman P; Division of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA., Lystig T; BridgeBio Pharma, Inc., San Francisco, CA., Cao X; BridgeBio Pharma, Inc., San Francisco, CA., Wang K; BridgeBio Pharma, Inc., San Francisco, CA., Pecoraro ML; BridgeBio Pharma, Inc., San Francisco, CA., Tamby JF; BridgeBio Pharma, Inc., San Francisco, CA., Katz L; BridgeBio Pharma, Inc., San Francisco, CA., Sinha U; BridgeBio Pharma, Inc., San Francisco, CA., Fox JC; BridgeBio Pharma, Inc., San Francisco, CA., Maurer MS; Department of Medicine, Columbia University Irving Medical Center, New York, NY.
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2024 Nov 18. Date of Electronic Publication: 2024 Nov 18.
DOI:	10.1161/CIRCULATIONAHA.124.072771
Abstrakt:	Background: In the phase 3 randomized controlled study, ATTRibute-CM, acoramidis, a transthyretin (TTR) stabilizer, demonstrated significant efficacy on the primary endpoint. Participants with transthyretin amyloid cardiomyopathy (ATTR-CM) who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report 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 (M30) in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through M30 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 (M42) 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 N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), serum TTR, and the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS). Safety outcomes were analyzed through M42. Results: Overall, 438 of 632 participants in ATTRibute-CM completed treatment and 389 enrolled in the ongoing OLE (263 continuous acoramidis, 126 placebo to acoramidis). The hazard ratio (HR) (95% CI) for ACM or first CVH was 0.57 (0.46, 0.72) at M42 based on a stratified Cox proportional hazards model ( P -value < 0.0001) favoring continuous acoramidis. Similar analyses were performed on ACM alone and first CVH alone, with HRs (95% CI) of 0.64 (0.47, 0.88) and 0.53 (0.41, 0.69), respectively, at M42. Treatment effects for NT-proBNP and 6MWD also favored continuous acoramidis. Upon initiation of open-label acoramidis in the placebo-to-acoramidis arm there was a prompt increase in serum TTR. Quality of life assessed by KCCQ-OS 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 M42 of the ongoing OLE study was associated with sustained clinical benefits in a contemporary ATTR-CM cohort, with no clinically important safety issues newly identified.
Databáze:	MEDLINE
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