Coramitug, a humanized monoclonal antibody for the treatment of transthyretin amyloid cardiomyopathy: a phase 2, randomized, multicenter, double-blind, placebo-controlled trial
BACKGROUND: Transthyretin amyloidosis with cardiomyopathy is a progressive disease caused by the - deposition of transthyretin (TTR) as amyloid in the myocardium. Current therapies - may slow disease progression but do not clear existing deposits. Coramitug is a humanized - monoclonal antibody that...
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| Auteurs principaux: | , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Langue: | anglais |
| Publié: |
27 January 2026
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| In: |
Circulation
Year: 2026, Volume: 153, Numéro: 4, Pages: 214-225 |
| ISSN: | 1524-4539 |
| Accès en ligne: | Verlag, lizenzpflichtig, Volltext: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.077304
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| Notes sur l'auteur: | Marianna Fontana, MD, Pablo García-Pavía, MD, Martha Grogan, MD, Sanjiv J. Shah, MD, Mads D.M. Engelmann, MD, G. Kees Hovingh, MD, Arnt V. Kristen, MD, Michelle Z. Lim-Watson, PhD, Brian Malling, MD, Soumitra Kar, MSc, Manjunatha Revanna, MD, Nitasha Sarswat, MD, Kenichi Tsujita, MD, Kevin M. Alexander, MD, and Mathew S. Maurer, MD |
| Résumé: | BACKGROUND: Transthyretin amyloidosis with cardiomyopathy is a progressive disease caused by the - deposition of transthyretin (TTR) as amyloid in the myocardium. Current therapies - may slow disease progression but do not clear existing deposits. Coramitug is a humanized - monoclonal antibody that targets misfolded transthyretin, designed to promote clearance - of transthyretin amyloid through antibody-mediated phagocytosis. METHODS: This phase 2, double-blind, placebo-controlled trial randomized participants with - transthyretin amyloidosis with cardiomyopathy to receive infusions every 4 weeks of - either coramitug at 2 dosages (10 mg/kg or 60 mg/kg) or placebo in a 1:1:1 ratio for - 52 weeks. The primary end points were the change from baseline to week 52 in the 6-minute - walk test and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Safety - was assessed for up to 64 weeks by assessing treatment-emergent adverse events, all-cause - mortality, and number of cardiovascular events (comprising hospitalization caused - by cardiovascular events or urgent heart failure visits). RESULTS: In total, 104 participants (median age, 77 years; 93% men; 84% New York Heart Association - class II; 13% with variant transthyretin amyloidosis with cardiomyopathy) were randomized - and dosed: 34 to 10 mg/kg of coramitug, 35 to 60 mg/kg of coramitug, and 35 to placebo. - Median NT-proBNP was 1985 pg/mL (interquartile range, 1224, 3406). In total, 90% of - participants were receiving disease-modifying therapy; 84% were treated with tafamidis - and 7 (6.7%) with transthyretin silencers (patisiran, n=4; vutrisiran, n=3). From - baseline to week 52, 60 mg/kg of coramitug significantly reduced NT-proBNP levels - compared with placebo (-48% [95% CI, -65% to -22%]; P=0.0017). The change in 6-minute walk test from baseline to week 52 was not statistically - different from placebo with either dose. Coramitug (60 mg/kg) was associated with - improved functional echocardiographic parameters and was well tolerated. CONCLUSIONS: This phase 2 trial showed that coramitug, an antibody targeting misfolded transthyretin - in transthyretin amyloidosis with cardiomyopathy, was well tolerated and, at a dose - of 60 mg/kg, resulted in a statistically significant reduction in NT-proBNP, a validated - marker of disease progression, with no statistically significant effect on 6-minute - walk test within 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05442047. |
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| Description: | Gesehen am 05.06.2026 |
| Description matérielle: | Online Resource |
| ISSN: | 1524-4539 |