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Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid
Quick Takes
- The use of the human anti-ATTR antibody NI006 in patients with ATTR cardiomyopathy and chronic heart failure was safe without serious adverse events.
- NI006 was associated with changes in extracellular volume on cardiac MRI and cardiac tracer uptake on scintigraphy, and changes in levels of cardiac biomarkers and functional measures.
- These findings warrant additional larger clinical studies of NI006 in patients with ATTR cardiomyopathy powered for hard clinical outcomes.
Study Questions:
What is the safety and side-effect profile of intravenous infusions of NI006 in patients with transthyretin amyloid (ATTR) cardiomyopathy?
Methods:
The investigators conducted a phase 1, double-blind trial, and 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/kg 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 immunoglobulin G antibody, and no antidrug antibodies were detected. At doses of ≥10 mg/kg, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac magnetic resonance imaging (MRI), 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:
The authors report that the use of NI006 was associated with no apparent drug-related serious adverse events in this phase 1 trial of NI006 for the treatment of patients with ATTR cardiomyopathy and heart failure.
Perspective:
This phase 1 trial reports the safety of the human anti-ATTR antibody NI006 in patients with ATTR cardiomyopathy and chronic heart failure. The use of NI006, particularly at doses of ≥10 mg/kg given every 4 weeks, was associated with changes in extracellular volume on cardiac MRI and cardiac tracer uptake on scintigraphy, two imaging-based surrogate markers of cardiac amyloid load. Furthermore, these imaging findings were accompanied by changes in levels of cardiac biomarkers and functional measures. These findings appear to support the proof-of-concept regarding the use of NI006 for the treatment of patients with ATTR cardiomyopathy and warrant additional larger clinical studies powered for hard outcomes.
Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Magnetic Resonance Imaging, Nuclear Imaging
Keywords: Amyloidosis, Biomarkers, Cardiomyopathies, Diagnostic Imaging, Heart Failure, Immunoglobulin G, Magnetic Resonance Imaging, Natriuretic Peptide, Brain, Prealbumin, Radionuclide Imaging, Troponin T
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