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Thyroid Biology and Disease

ORF49-04 - Characterization of Proptosis Response in the THRIVE Phase 3 Trial of Veligrotug for Active Thyroid Eye Disease (TED)

Monday, June 15, 2026
2:00 PM - 2:15 PM CT
Location: Room W184ABC
Disclosure(s):
Madhura Tamhankar, MD: Amgen: Advisory Board (), Consultant (), Speakers' Bureau (); Argenx: Advisory Board (), Consultant (); Dompe: Advisory Board (); Genentech: Advisory Board (), Consultant (); UpToDate: Royalty for chapter (); Viridian: Advisory Board (), Consultant ()



Introduction:
TED is a debilitating autoimmune condition that causes orbital inflammation and tissue expansion. Veligrotug, an investigational full antagonist monoclonal antibody to the IGF-1 receptor, demonstrated statistically significant improvement across key clinical domains in the phase 3 THRIVE trial in patients with active TED (NCT05176639). This analysis further characterizes the magnitude of proptosis response at the individual-patient level, enhancing understanding of veligrotug’s effect across the population.

Methods:
Adults with moderate-to-severe active TED (onset ≤15 months, proptosis ≥3 mm above normal, and clinical activity score [CAS] ≥3) were randomized to receive veligrotug (10 mg/kg) or placebo, each administered once every 3 weeks for a total of 5 IV infusions. Proptosis was assessed by Hertel exophthalmometry through Week 15. Proptosis responders were defined as patients who had ≥2 mm reduction in the study eye without a corresponding increase of ≥2 mm in the fellow eye.

Results:
Among 113 patients (veligrotug, n=75; placebo, n=38) in the intent-to-treat population, proptosis was significantly improved in the veligrotug vs the placebo group at Week 15, with a mean reduction of 2.9 mm vs 0.5 mm (p < 0.0001). Of 107 patients (veligrotug, n=69; placebo, n=38) with both baseline and Week 15 proptosis measurements, 71% vs 5% of veligrotug vs placebo patients were proptosis responders. Proptosis reduction of ≥3 mm occurred in 55% vs 3% and reduction of ≥4 mm occurred in 23% vs 0% of veligrotug vs placebo patients. Proptosis increased in 21% of placebo-treated but in none of the veligrotug-treated patients. Individual-patient proptosis reduction will be shown across the whole population in presentation. Among veligrotug responders, proptosis reduction (mean ± SD) was observed as early as Week 3 (2.4 ± 1.2 mm) and continued through Week 15 (3.7 ± 1.4 mm). Veligrotug was generally well tolerated, with mostly mild adverse events, no serious treatment-related adverse events, and a low treatment discontinuation rate.

Conclusion:
A 12-week 5-infusion treatment regimen of 10 mg/kg veligrotug was generally well tolerated and led to significant improvement in proptosis among patients with active TED. No increase in proptosis was observed in veligrotug-treated patients, and among the 71% who were responders, a substantial proptosis reduction (mean 3.7 mm) was observed at Week 15. Assessing proptosis reduction at the individual‑patient level may better inform treatment expectations.