{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:36:10Z","timestamp":1792859770507,"version":"4.5.0"},"reference-count":14,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novo Nordisk A\/S","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,1,27]]},"abstract":"\n BACKGROUND:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n 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).<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n 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 (\u201348% [95% CI, \u201365% to \u201322%];\n P<\/jats:italic>\n =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.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n REGISTRATION:<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: NCT05442047.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.125.077304","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T20:00:10Z","timestamp":1762804810000},"page":"214-225","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Coramitug, a Humanized Monoclonal Antibody for the Treatment of Transthyretin Amyloid Cardiomyopathy: A Phase 2, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9233-9831","authenticated-orcid":true,"given":"Marianna","family":"Fontana","sequence":"first","affiliation":[{"name":"National Amyloidosis Centre, University College London (Royal Free Campus), United Kingdom (M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-2257","authenticated-orcid":true,"given":"Pablo","family":"Garc\u00eda-Pav\u00eda","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Puerta de Hierro de Majadahonda, Health Research Institute of the Puerta de Hierro Majadahonda-Segovia de Arana, Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Cardiovasculares (CIBER-CV),and Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (P.G.-P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2541-4440","authenticated-orcid":true,"given":"Martha","family":"Grogan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Mayo Clinic, Rochester, MN (M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-8201","authenticated-orcid":true,"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (S.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads D.M.","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (M.D.M.E, G.K.H., M.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Kees","family":"Hovingh","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (M.D.M.E, G.K.H., M.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnt V.","family":"Kristen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, and Pneumology, Medical University of Heidelberg, Germany (A.V.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-2931","authenticated-orcid":true,"given":"Michelle Z.","family":"Lim-Watson","sequence":"additional","affiliation":[{"name":"Novo Nordisk US Research & Development, Lexington, MA (M.L.-W., B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8570-4327","authenticated-orcid":true,"given":"Brian","family":"Malling","sequence":"additional","affiliation":[{"name":"Novo Nordisk US Research & Development, Lexington, MA (M.L.-W., B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1701-0347","authenticated-orcid":true,"given":"Soumitra","family":"Kar","sequence":"additional","affiliation":[{"name":"Novo Nordisk Service Centre Pvt Ltd, Bangalore, India (S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjunatha","family":"Revanna","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (M.D.M.E, G.K.H., M.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0233-7881","authenticated-orcid":true,"given":"Nitasha","family":"Sarswat","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, University of Chicago Medicine, IL (N.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-259X","authenticated-orcid":true,"given":"Kenichi","family":"Tsujita","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan (K.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4024-3691","authenticated-orcid":true,"given":"Kevin M.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Stanford Amyloid Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (K.M.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-5008","authenticated-orcid":true,"given":"Mathew S.","family":"Maurer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.0442"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2409134"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2305434"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805689"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2303765"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2024.2420809"},{"key":"e_1_3_3_8_2","unstructured":"World Medical Association. 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