Preliminary Safety, Efficacy, and Quality of Life Outcomes of Subcutaneous Lonigutamab (Anti–Insulin-Like Growth Factor 1 Receptor [IGF-1R]) from a Phase 1/2 Proof of Concept Study in Patients with Thyroid Eye Disease (TED)
Author: Jwu Jin Khong
Base Hospital / Institution: Centre for Eye Research Australia
Rapid fire oral presentation
Abstract ID: 24-330
Purpose
To evaluate subcutaneous (SC) lonigutamab (Loni; anti–IGF-1R) in patients (pts) with active TED (NCT05683496).
Methods
Eligible pts have proptosis ≥3 mm above normal range in the study eye and a Clinical Activity Score (CAS) ≥4. Cohort 1 (completed) received Loni 40 mg or placebo (pbo) every 3 wk (2 doses); wk 6 and 12 data are shown. Cohort 2 (ongoing) received Loni 50 mg (loading dose) and 25 mg weekly (11 doses); wk 6 data are shown.
Results
Cohort 1 enrolled 8 pts (Loni, n=6; pbo, n=2 [1 with evaluable post-baseline (BL) data]). At wk 6 and 12, 3/6 (50%) Loni pts and 0% of pbo pts had a proptosis response. Among pts with BL diplopia, 1/4 (25%) Loni pts and 0% of pbo pts had a diplopia response at wk 6 and 12. In the Loni group, 6/6 (100%) pts achieved a clinically meaningful reduction (≥2 points) in CAS in the study eye at wk 6 and 12 vs 0% of pbo pts. Mean (SD) overall Graves’ Ophthalmopathy Quality of Life (GO-QoL) change from BL was 12.9 (13.9) and 12.3 (9.7) at wk 6 and 12 with Loni (vs −15.6 at wk 6 and 12 for 1 pbo pt; higher scores indicate better health). Treatment-emergent adverse events (TEAEs) occurred in 4/6 (67%) Loni and 2/2 (100%) pbo pts; all were grade 1–2 (1 grade 2), with no serious AEs (SAEs). In the Loni group, 3 pts had AEs of special interest (AESIs; all tinnitus, no changes on audiogram).
In cohort 2, at wk 6, 4/6 (67%) pts had a proptosis response. In pts with BL diplopia, 2/5 (40%) had a diplopia response. At wk 6, 5/6 (83%) pts achieved a ≥2-point reduction in CAS in the study eye. Mean (SD) overall GO-QoL change was 21.1 (15.0). TEAEs were reported in 5/6 (83%) pts; all were grade 1–2 with no AESIs or SAEs.
Conclusion
These findings are the first reported proof-of-concept results of a SC anti–IGF-1R in pts with TED (cohort 1). Pts achieved early clinical responses that were maintained over the time points evaluated, including at wk 12 (off treatment), supporting the potential for longer dosing intervals. Evidence from cohort 1 suggests Loni was well tolerated and displayed clinical efficacy and QoL responses, which is further substantiated by cohort 2 data.
Additional Authors
| First name | Last name | Base Hospital / Institution |
|---|---|---|
| David | Kostick | Florida Eye Specialists |
| Jane | Spadaro | Department of Ophthalmology, Corewell Health William Beaumont University Hospital and Kahana Oculoplastic and Orbital Surgery |
| Anita | Grover | ACELYRIN, INC. |
| So Jung | Imm | ACELYRIN, INC. |
| Sarah | Chesler | ACELYRIN, INC. |
| Shephard | Mpofu | ACELYRIN, INC. |
| Shoaib | Ugradar | Department of Orbital and Oculoplastic Surgery, Thrive Health |
