• Pablo Garcia-Pavia, Fabian Aus dem Siepen, Erwan Donal, Olivier Lairez, Peter van der Meer, Arnt V Kristen, Michele F Mercuri, Aubin Michalon, FrostRobert J ARJAFrom Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares, Madrid, and Universidad Francisco de Vitoria, Pozuelo de Alarcón - all in Spain (P.G.-P.); the Departme, Jan Grimm, Roger M Nitsch, Christoph Hock, Peter C Kahr, and Thibaud Damy.
• From Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares, Madrid, and Universidad Francisco de Vitoria, Pozuelo de Alarcón - all in Spain (P.G.-P.); the Department of Cardiology, University Hospital Heidelberg, Heidelberg (F.S.), and Cardiovascular Center Darmstadt, Darmstadt (A.V.K.) - both in Germany; the Department of Cardiology, University of Rennes, Centre Hospitalier Universitaire (CHU) de Rennes, INSERM, LTSI-UMR 1099, Rennes (E.D.), Service de Cardiologie, CHU de Toulouse-Hôpital Rangueil, Toulouse (O.L.), and the Cardiology Department and French National Reference Center for Cardiac Amyloidosis, Hôpitaux Universitaires Henri Mondor, Assistance Publique-Hôpitaux de Paris, and Institut Mondor de Recherche Biomédicale, INSERM, Université Paris Est Créteil, Créteil (T.D.) - all in France; the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.M.); Alexion-AstraZeneca Rare Disease, Boston (M.F.M.); and Neurimmune (A.M., R.J.A.F., J.G., R.M.N., C.H., P.C.K.) and the Institute for Regenerative Medicine (R.M.N., C.H.) and the Center for Molecular Cardiology (P.C.K.), University of Zurich - all in Schlieren, Switzerland.
• N. Engl. J. Med. 2023 Jul 20; 389 (3): 239250239-250.

BackgroundTransthyretin amyloid (ATTR) cardiomyopathy is a progressive and fatal disease caused by misfolded transthyretin. Despite advances in slowing disease progression, there is no available treatment that depletes ATTR from the heart for the amelioration of cardiac dysfunction. NI006 is a recombinant human anti-ATTR antibody that was developed for the removal of ATTR by phagocytic immune cells.MethodsIn this phase 1, double-blind trial, we randomly assigned (in a 2:1 ratio) 40 patients with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive intravenous infusions of either NI006 or placebo every 4 weeks for 4 months. Patients were sequentially enrolled in six cohorts that received ascending doses (ranging from 0.3 to 60 mg per kilogram of body weight). After four infusions, patients were enrolled in an open-label extension phase in which they received eight infusions of NI006 with stepwise increases in the dose. The safety and pharmacokinetic profiles of NI006 were assessed, and cardiac imaging studies were performed.ResultsThe use of NI006 was associated with no apparent drug-related serious adverse events. The pharmacokinetic profile of NI006 was consistent with that of an IgG antibody, and no antidrug antibodies were detected. At doses of at least 10 mg per kilogram, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac magnetic resonance imaging, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over a period of 12 months. The median N-terminal pro-B-type natriuretic peptide and troponin T levels also seemed to be reduced.ConclusionsIn this phase 1 trial of the recombinant human antibody NI006 for the treatment of patients with ATTR cardiomyopathy and heart failure, the use of NI006 was associated with no apparent drug-related serious adverse events. (Funded by Neurimmune; NI006-101 ClinicalTrials.gov number, NCT04360434.).Copyright © 2023 Massachusetts Medical Society.

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