Cliramitug for depletion of cardiac amyloid transthyretin: long-term follow-up of the NI006-101 trial
Abstract
In a first-in-human trial (NI006-101), the monoclonal antibody cliramitug, targeting misfolded transthyretin, demonstrated a favorable safety profile and time- and dose-dependent reductions in surrogate markers of cardiac amyloid burden over the course of 12 months in patients with amyloid transthyretin cardiomyopathy (ATTR-CM). Here we evaluate the long-term safety and efficacy of cliramitug in a subgroup of participants of the NI006-101 trial who continued treatment in a second open-label extension (OLE2) and further explore dose- and time-dependent effects on amyloid depletion, cardiac biomarkers and cardiac structure and function. Twenty-three participants (20 receiving background treatment with tafamidis, all male) entered OLE2 and received a median of 10 additional infusions, increasing the maximum total exposure to 24 infusions and extending the median follow-up to 29.3 months. Thirteen participants initially treated with ≤10 mg kg-1 were up-titrated to 30 mg kg-1 during OLE2. Treatment adherence was high (98%), with no treatment-related serious adverse events or discontinuations. Continued treatment and up-titration in participants with lower prior exposure led to further reductions in cardiac extracellular volume on MRI and tracer uptake on bisphosphonate scintigraphy. Improvements were also observed in NT-proBNP and troponin T levels, left ventricular relaxation, filling pressures and wall thickness. Increases in Kansas City Cardiomyopathy Questionnaire scores suggested potential quality-of-life benefits. Consistent with results from the original trial, cliramitug showed favorable long-term safety and further reductions in cardiac amyloid burden following up-titration to 30 mg kg-1. These time- and dose-dependent improvements across structural, functional and biomarker endpoints support the therapeutic potential of amyloid-depleting therapy with cliramitug in ATTR-CM. ClinicalTrials.gov: NCT04360434 .
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BibTeX
@article{kahr2026cliramitug,
title = {{Cliramitug for depletion of cardiac amyloid transthyretin: long-term follow-up of the NI006-101 trial}},
author = {Peter C. Kahr and Fabian Aus Dem Siepen and Olivier Lairez and Erwan Donal and Thibaud Damy and Arnt V. Kristen and Cristina C. Quarta and Michele F. Mercuri and Sarah Keppner-Witter and Eva Herrmann-Keiner and Mia Tichy and Aubin Michalon and Jan Grimm and Roger M. Nitsch and Christoph Hock and Pablo Garcia-Pavia and Peter van der Meer},
journal = {Nature Medicine},
year = {2026},
month = oct,
doi = {10.1038/s41591-026-04487-3},
url = {https://hal.science/hal-05825700v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Cliramitug for depletion of cardiac amyloid transthyretin: long-term follow-up of the NI006-101 trial
AU - Peter C. Kahr
AU - Fabian Aus Dem Siepen
AU - Olivier Lairez
AU - Erwan Donal
AU - Thibaud Damy
AU - Arnt V. Kristen
AU - Cristina C. Quarta
AU - Michele F. Mercuri
AU - Sarah Keppner-Witter
AU - Eva Herrmann-Keiner
AU - Mia Tichy
AU - Aubin Michalon
AU - Jan Grimm
AU - Roger M. Nitsch
AU - Christoph Hock
AU - Pablo Garcia-Pavia
AU - Peter van der Meer
PY - 2026
DA - 2026/10/20
JO - Nature Medicine
DO - 10.1038/s41591-026-04487-3
UR - https://hal.science/hal-05825700v1
AB - In a first-in-human trial (NI006-101), the monoclonal antibody cliramitug, targeting misfolded transthyretin, demonstrated a favorable safety profile and time- and dose-dependent reductions in surrogate markers of cardiac amyloid burden over the course of 12 months in patients with amyloid transthyretin cardiomyopathy (ATTR-CM). Here we evaluate the long-term safety and efficacy of cliramitug in a subgroup of participants of the NI006-101 trial who continued treatment in a second open-label extension (OLE2) and further explore dose- and time-dependent effects on amyloid depletion, cardiac biomarkers and cardiac structure and function. Twenty-three participants (20 receiving background treatment with tafamidis, all male) entered OLE2 and received a median of 10 additional infusions, increasing the maximum total exposure to 24 infusions and extending the median follow-up to 29.3 months. Thirteen participants initially treated with ≤10 mg kg-1 were up-titrated to 30 mg kg-1 during OLE2. Treatment adherence was high (98%), with no treatment-related serious adverse events or discontinuations. Continued treatment and up-titration in participants with lower prior exposure led to further reductions in cardiac extracellular volume on MRI and tracer uptake on bisphosphonate scintigraphy. Improvements were also observed in NT-proBNP and troponin T levels, left ventricular relaxation, filling pressures and wall thickness. Increases in Kansas City Cardiomyopathy Questionnaire scores suggested potential quality-of-life benefits. Consistent with results from the original trial, cliramitug showed favorable long-term safety and further reductions in cardiac amyloid burden following up-titration to 30 mg kg-1. These time- and dose-dependent improvements across structural, functional and biomarker endpoints support the therapeutic potential of amyloid-depleting therapy with cliramitug in ATTR-CM. ClinicalTrials.gov: NCT04360434 .
SN - 1078-8956
SN - 1744-7933
ER -