Positive Safety, Pharmacokinetic Profile Observed for NI006 in ATTR Cardiomyopathy Trial


Data from a phase 1, first-in-human trial of NI006 suggests the agent could have a potential role in the management of transthyretin amyloid cardiomyopathy.

Pablo Garcia-Pavia, MD, PhD | Credit: Twitter

Pablo Garcia-Pavia, MD, PhD
Credit: Twitter

Data from a phase 1 proof-of-concept study provides insight into the safety, tolerability, and pharmacology of NI006 in patients with transthyretin amyloid (ATTR) cardiomyopathy.

Funded by Neurimmune AG, results of the study suggest use of NI006, a recombinant human antibody designed to deplete amyloid deposits in ATTR cardiomyopathy, was associated with possible reductions in NT-proBNP and troponin T levels without the presence of drug-related serious adverse events at 12 months among patients with wild-type or variant ATTR cardiomyopathy and chronic heart failure.1

“The depletion of the cardiac ATTR deposits is a rational therapeutic target to revert disease pathology and restore organ function”, said principal investigator Pablo Garcia-Pavia, MD, PhD, head of the Inherited Cardiac Diseases and Heart Failure Unit at the Hospital Universitario Puerta de Hierro and the Spanish National Cardiovascular Research Institute in Madrid, Spain.2 “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.”

A first-in-human investigation, the phase 1 trial consisting of 2 parts, the NI006-101 trial was designed with a 4-month, double-blind, placebo-controlled, international, multicenter, combined single-ascending-dose phase and an 8-month, multiple-ascending-dose, randomized clinical trial with an open-label extension phase. Led by Garcia-Pavia, the trial enrolled adult patients with ATTR cardiomyopathy between February 2020 through April 2022 from 6 specialized amyloidosis centers in 4 European countries.1

For inclusion in the trial, patients needed to have a confirmed diagnosis of ATTR cardiomyopathy, a left ventricular wall thickness of at least 14 mm, a left ventricular ejection fraction of at least 40%, meet criteria for New York Heart Association class I, II, or III heart failure, an eGFR of more than 30 ml/min/1.73 m2, and an NT-proBNP level of 600 to 6000 pg/mL.1

Overall, 40 patients were enrolled in the trial. Of these, 27 were randomized to NI006 and 13 were randomized to placebo. This cohort had a median age 72 (range, 28 to 87) years, 39 were male, 33 had wild-type ATTR cardiomyopathy, and 36 had been receiving treatment with tafamadis, with a median treatment duration of . Investigators noted those randomized to NI006 appeared to have more advanced disease than those randomized to placebo therapy.1

Per trial protocol, patients were randomized in a 2:1 ratio to receive intravenous infusions of NI006 or placebo therapy every 4 weeks for 4 months. For the purpose of analysis, patients were sequentially enrolled in 6 cohorts receiving ascending doses ranging from 0.3 to 60 mg per kg of body weight. Following this 4-month period, all patients received NI006 with stepwise increases dose for the 8-month open-label extension period.1

Initial analysis revealed high levels of adherence to trial protocol, with 34 patients received all four scheduled infusions and 34 of 35 patients completing the 4-month, double-blind portion of the trial subsequently enrolled in the 8-month, open-label phase.1

Analysis of the safety profile from the trial revealed there were no apparent drug-related serious adverse events with use of NI006. Overall, 37 patients had at least one adverse event during the trial. Investigators noted most of these adverse events were considered to be mild or moderate in intensity. Additionally, the most frequently observed adverse events were heart failure and arrhythmia, which investigators suggested are common in this patient population.1

Investigators pointed out there was an apparent increase in the number of musculoskeletal events when using ascending doses of NI006. This apparent increase was present among those using NI006 in the double-blind phase, but also in those who switched to NI006 in the open-label phase. Investigators underlined the majority of these events were mild and were treated with nonsteroidal antiinflammatory drugs or low-dose glucocorticoids, with the course tapered off during continued treatment with NI006.1

Analysis of the pharmacokinetic profile of NI006 revealed the profile was consistent with that of an IgG antibody and no antidrug antibodies were detected by investigators. Further analysis indicated NI006, at doses of at least 10 mg/kg, were associated with an apparent reduction in cardiac tracer uptake on scintigraphy and extracellular volume on cardiac magnetic resonance imaging at 12 months. Investigators also highlighted apparent reductions in NT-proBNP and troponin T levels during the trial.1


  1. Garcia-Pavia P, Aus dem Siepen F, Donal E, et al. Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid. N Engl J Med. 2023;389(3):239-250. doi:10.1056/NEJMoa2303765
  2. Promising phase 1 results for antibody NI006 in ATTR cardiomyopathy published in the New England Journal of Medicine. Neurimmune. May 20, 2023. Accessed July 25, 2023. https://www.neurimmune.com/news/ni006phase1.
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