The following is a summary of “Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid,” published in the July 2023 issue of Cardiology by Garcia-Pavia et al.
In the retrospective study, researchers aimed to assess the safety and pharmacokinetic profiles of a recombinant human anti-ATTR antibody, NI006, developed to promote ATTR removal via phagocytic immune cells in ATTR cardiomyopathy and chronic heart failure. Transthyretin amyloid (ATTR) cardiomyopathy is a deadly disease caused by misfolded transthyretin, and no current treatment is available to remove ATTR from the heart for cardiac dysfunction improvement.
Phase 1 randomly enrolled 40 patients with wild-type or variant ATTR cardiomyopathy and chronic heart failure assigned in a ratio 2:1 to receive NI006 or placebo through intravenous infusions every 4 weeks over 4 months. Patients were categorized into six groups, each receiving increasing doses (ranging from 0.3 to 60 mg per kilogram of body weight). After four infusions of NI006, patients were moved to the next phase, an open-label extension phase, where patients had eight times more infusions of NI006 with increased doses.
Patients enrolled in the study didn’t show any severe adverse effects. A consistent pharmacokinetic profile of NI006 was observed with an IgG antibody, and there were no signs of developing anti-drug antibodies. Additionally, about 10 mg/kg dose of NI006 has shown positive impacts on cardiac amyloid load by reduced cardiac tracer uptake on scintigraphy and reduced extracellular volume on cardiac magnetic resonance imaging over 12 months. Additionally, median levels of N-terminal pro–B-type natriuretic peptide and troponin T also showed lessening, indicating potential improvements in cardiac function.
The study concluded that a recombinant human antibody demonstrated a favorable safety profile with no apparent drug-related serious adverse events in patients with ATTR cardiomyopathy and heart failure.