Amyloid transthyretin cardiomyopathy (ATTR-CM) is an underdiagnosed, systemic condition that leads to progressive heart failure and high rate of fatality within four years from diagnosis.
Progressive ATTR amyloid depositions characterize the disease, causing heart failure and death. Despite recent advances and approved therapies, there remains significant unmet medical need in treating moderate to severe ATTR-CM and amyloid depletion may constitute an important new mechanism to achieve further effectiveness.
NI006 has been designed to target the pathology of ATTR-CM by enabling depletion of amyloid fibrils in the heart. This phase 1 study investigated safety, tolerability, pharmacology, and efficacy at 12 months of NI006 treatment in ascending doses.
Results indicate that the safety profile of NI006 is favorable up to the highest dose tested. No apparent dose-limiting toxic effects or drug-related serious adverse reactions were observed.
The pharmacokinetic profile was consistent with that of an IgG antibody, and no antidrug antibodies were detected. At doses of at least 10 mg per kilogram, cardiac amyloid deposition, detected by either scintigraphy or cardiac magnetic resonance imaging, was substantially reduced over a period of 12 months.
Reductions were also seen in levels of biomarkers measuring cardiac stress and cardiomyocyte death, N-terminal pro-B-type natriuretic peptide and troponin T.
"The depletion of the cardiac ATTR deposits is a rational therapeutic target to revert disease pathology and restore organ function,” said Dr. Pablo Garcia-Pavia from the Hospital Universitario Puerta de Hierro and CNIC in Madrid, Spain, and principal investigator of the study.
“The results of this study are very promising and show initial evidence that NI006 acts as a depleter of cardiac amyloid load with potential to improve cardiac structure, function and outcomes in ATTR cardiomyopathy.”