Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid

This first-in-human phase 1 trial evaluated NI006, a recombinant human monoclonal antibody designed to selectively bind and clear misfolded transthyretin (TTR) amyloid from cardiac tissue in patients with ATTR cardiomyopathy and heart failure. Forty patients (33 with wild-type ATTR, 36 on tafamidis) were randomized 2:1 to receive ascending doses of NI006 (0.3–60 mg/kg) or placebo via IV infusion every 4 weeks for 4 months, followed by an 8-month open-label extension. NI006 was well tolerated, with no drug-related serious adverse events or antidrug antibodies. Imaging markers, including cardiac tracer uptake on scintigraphy and extracellular volume on cardiac MRI, showed apparent reductions at ≥10 mg/kg. Cardiac biomarkers (NT-proBNP and troponin T) also declined, and exploratory quality-of-life and functional assessments (KCCQ-OS, 6-minute walk distance) indicated potential improvement. Arthralgias and mild cytokine release were noted at higher doses. Overall, results support further investigation into NI006’s safety and efficacy for cardiac ATTR amyloid depletion.

This first-in-human phase 1 trial evaluated NI006, a recombinant human monoclonal antibody designed to selectively bind and clear misfolded transthyretin (TTR) amyloid from cardiac tissue in patients with ATTR cardiomyopathy and heart failure. Forty patients (33 with wild-type ATTR, 36 on tafamidis) were randomized 2:1 to receive ascending doses of NI006 (0.3–60 mg/kg) or placebo via IV infusion every 4 weeks for 4 months, followed by an 8-month open-label extension. NI006 was well tolerated, with no drug-related serious adverse events or antidrug antibodies. Imaging markers, including cardiac tracer uptake on scintigraphy and extracellular volume on cardiac MRI, showed apparent reductions at ≥10 mg/kg. Cardiac biomarkers (NT-proBNP and troponin T) also declined, and exploratory quality-of-life and functional assessments (KCCQ-OS, 6-minute walk distance) indicated potential improvement. Arthralgias and mild cytokine release were noted at higher doses. Overall, results support further investigation into NI006’s safety and efficacy for cardiac ATTR amyloid depletion.