Anti-ATTR Antibody NI006 Shows Cardiac Amyloid Depletion on Imaging in Phase 1 Trial
In this phase 1 trial of 40 patients with transthyretin amyloid cardiomyopathy, the recombinant human antibody NI006 administered intravenously every four weeks appeared safe with no drug-related serious adverse events. At doses of 10 mg/kg or higher, cardiac tracer uptake on scintigraphy and extracellular volume on MRI decreased over 12 months, accompanied by reductions in NT-proBNP and troponin T, suggesting the first evidence of active cardiac amyloid clearance by antibody therapy.
The original study
Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid.
- Authors
- Garcia-Pavia P, Aus dem Siepen F, Donal E, Lairez O, van der Meer P, Kristen AV, et al.
- Journal
- The New England journal of medicine
- Type
- Clinical Trial, Phase I, Randomized Controlled Trial, Journal Article
- PMID
- 37212440
Original abstract
BACKGROUND: Transthyretin 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. METHODS: In 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. RESULTS: The 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. CONCLUSIONS: In 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.).