Week 12 Data From a Phase 1/2 Proof-of-Concept Study of Subcutaneous Lonigutamab (Anti-IGF-1R) in Patients With Thyroid Eye Disease

Document Type

Conference Proceeding

Publication Date

2-2026

Publication Title

Clinical and Experimental Ophthalmology

Abstract

Purpose: Thyroid eye disease (TED) is a chronic, vision-threatening condition centrally mediated by aberrant stimulation of the insulin-like growth factor 1 receptor (IGF-1R) pathway. Despite treatment advances, opportunity exists for durable multifaceted responses and improved safety to reduce treatment-limiting side effects seen with competitive anti–IGF-1Rs. This phase 1/2 dose-ranging study evaluated subcutaneous lonigutamab, a high-affinity, noncompetitive, anti-IGF-1R monoclonal antibody, for the treatment of active TED (NCT05683496). Methods: Patients received lonigutamab 40 mg or placebo every three weeks (two doses; 40 mg-Q3W), lonigutamab 50 mg every four weeks (three doses; 50 mg-Q4W), or lonigutamab 50 mg (loading dose) and 25 mg weekly (11 doses; 50 mg-load/25 mg-QW). Results: Eight patients were enrolled in each cohort (40 mg-Q3W: lonigutamab, n = 6; placebo, n = 2 [1 evaluable]). At week 12, 50% of patients in 40 mg-Q3W (vs. 0% in placebo), 25% in 50 mg-Q4W, and 63% in 50 mg-load/25 mg-QW cohorts had a proptosis response; 25% (vs. 0%), 60% and 50%, respectively, had a diplopia response; and 100% (vs. 0%), 63% and 100%, respectively, had a ≥ 2-point improvement in Clinical Activity Score. Lonigutamab also improved Graves’ Ophthalmopathy Quality of Life scores. Most treatment-emergent adverse events were mild, with no serious treatment-emergent adverse events. Tinnitus occurred in four lonigutamab-treated patients (all mild, no changes on audiogram). Conclusion: Evaluation of multiple dosing regimens showed that lonigutamab was well tolerated and demonstrated proof-of-concept for preliminary activity in TED. Data suggest that optimal clinical efficacy across TED manifestations was achieved when exposure was maintained above receptor saturation.

Volume

54

Issue

S1

First Page

28

Comments

RANZCO (Royal Australian and New Zealand College of Ophthalmologists) 56th Annual Congress, November 14-17, 2025, Melbourne, Australia

Last Page

28

DOI

10.1111/ceo.70049

Link to Full Text

Share

COinS