A phase 1 trial demonstrated that the antibody N1006 has an acceptable safety profile in treating patients with transthyretin amyloid cardiomyopathy (ATTR-CM), according to a study published in The New England Journal of Medicine. 

In ATTR amyloidosis, misfolded ATTR proteins may deposit in the cardiac extracellular spaces; this infiltration can cause myocardial stiffening, diastolic dysfunction, conduction abnormalities, and arrhythmias. Ultimately, it can lead to cardiac failure and early death. 

Despite therapeutic advancements, there are currently no therapies that deplete ATTR from the heart and reverse cardiac dysfunction. N1006 is a recombinant human anti-ATTR monoclonal IgG1 antibody that selectively binds to amyloid conformations of TTR (both hereditary and wild type), while avoiding physiologically folded TTR. The authors of the study conducted a first-in-human study assessing the merits of this intravenous drug in treating patients with ATTR-CM. 

The phase 1, multicenter trial was double-blinded, placebo-controlled, and combined ascending-dose and multiple-ascending-dose. Patients with ATTR-CM and chronic heart failure (n=40) were randomly assigned in a 2:1 ratio to receive intravenous infusions of N1006 or the placebo every 4 weeks for 4 months. Patients were sequentially enrolled into 6 cohorts receiving ascending doses, ranging from 0.3 to 60 mg/kg body weight. After 4 infusions, an 8-month open-label extension phase began during which all patients, including those receiving placebo, were administered N1006 with stepwise increases in dosing. 

Read more about ATTR-CM etiology

The patients underwent various evaluations during the trial, including serial bisphosphonate scintigraphy/cardiac magnetic resonance imaging, as well as evaluations of N-terminal prohormone of brain natriuretic peptide and troponin T levels, at 4 and 12 months. Serial serum N1006 concentrations were obtained throughout the study via a validated assay. Dose escalation was guided by assessing the presence/frequency of adverse events. 

The researchers reported that N1006 use was not associated with any apparent serious adverse events. Most reports of adverse events were mild to moderate and were not dose-dependent. The most frequently reported adverse events were heart failure and arrhythmias, which were expected in this cohort of patients. 

“The results of this phase 1 trial show the safety profile of NI006 in patients with ATTR cardiomyopathy and support additional clinical investigation of NI006 for the treatment of patients with ATTR cardiomyopathy,” the authors concluded. 


Garcia-Pavia P, Aus dem Siepen F, Donal E, et al. Phase 1 trial of antibody NI006 for depletion of cardiac transthyretin amyloidN Engl J Med. Published online July 20, 2023. doi:10.1056/NEJMoa2303765