Research Summary

Cliramitug Reduces Cardiac Amyloid Markers in ATTR-CM Extension

Anthony Calabro, MA

Key Highlights

  • Twenty-three participants with transthyretin amyloid cardiomyopathy continued cliramitug in the second open-label extension of NI006-101.
  • Cardiac MRI showed reduced extracellular volume in 12 of 13 participants with available data.
  • All 8 participants with available scintigraphy data had reduced cardiac tracer uptake.
  • No treatment-related serious adverse events or treatment discontinuations were reported.

Long-term treatment with cliramitug was associated with further reductions in imaging markers of cardiac amyloid burden among patients with transthyretin amyloid cardiomyopathy (ATTR-CM), according to findings from the NI006-101 trial published in Nature Medicine. Improvements were also observed in cardiac biomarkers, cardiac structure and function, and quality-of-life scores.

Cliramitug is an intravenous monoclonal antibody designed to bind misfolded and aggregated transthyretin and promote amyloid clearance. The second open-label extension, OLE2, evaluated its safety, tolerability, and exploratory efficacy beyond the first 12 months of the first-in-human, proof-of-concept trial.

Of 26 participants who completed 12 months in the original trial cohorts, 23 entered OLE2. All were men, their median age was 70 years, and 20 (87%) were receiving background tafamidis. Participants received 6 to 12 additional cliramitug infusions every 4 weeks. Thirteen participants with previous doses ≤10 mg/kg were titrated to 30 mg/kg.

Study Findings

Participants received a median of 10 additional infusions, increasing the maximum exposure to 24 infusions and extending median follow-up to 29.3 months. Treatment adherence was 98%.

Among 13 participants with cardiac MRI data at the end of OLE2, 12 (92%) had reductions in extracellular volume from baseline. The median absolute reduction was 10.5%, corresponding to a median relative reduction of 19.5%. All 8 participants with available scintigraphy data demonstrated reduced cardiac tracer uptake, with a median relative reduction of 36.1%.

N-terminal pro–B-type natriuretic peptide levels decreased from baseline in 17 of 21 participants, while troponin T levels decreased in 16 of 22. Improvements in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score occurred in 17 of 22 participants, including 13 with improvements of ≥5 points.

Seven participants (30%) experienced serious adverse events during OLE2, but none were considered related to cliramitug. No treatment-related serious adverse events, treatment-related discontinuations, or antidrug antibodies were reported.

Clinical Implications

According to the study authors, the findings support the therapeutic potential of directly depleting cardiac amyloid with cliramitug and support the dosing regimen being evaluated in the ongoing phase 3 DepleTTR-CM trial. That study is examining whether the observed changes in surrogate markers translate into reduced morbidity and improved survival.

The open-label extension was susceptible to bias, and its small sample and variable dosing limited definitive conclusions. Most participants also received background tafamidis, and follow-up remained insufficient to determine cliramitug’s effects on survival and other critical clinical outcomes.

Expert Commentary

“Cliramitug exhibited a favorable safety profile and encouraging reduction in surrogate markers of cardiac ATTR,” the researchers concluded.

Reference
Kahr PC, aus dem Siepen F, Lairez O, et al. Cliramitug for depletion of cardiac amyloid transthyretin: long-term follow-up of the NI006-101 trial. Nat Med. 2026;32:2639-2646. doi:10.1038/s41591-026-04487-3