Title: THRIVE Phase 3 Trial of Veligrotug in Active Thyroid Eye Disease (TED): Efficacy, Safety, and Quality of Life at 15 Weeks

Purpose:

Thyroid eye disease (TED) is a debilitating autoimmune condition that not only impairs visual function but also significantly affects daily life. Veligrotug, a full antagonist humanized monoclonal antibody targeting the IGF-1 receptor, is being evaluated for TED. Here, we report efficacy, safety, and Graves Ophthalmopathy Quality of Life (GO-QOL) outcomes from the phase 3 THRIVE randomized controlled trial of veligrotug in active TED (NCT05176639).

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 10 mg/kg veligrotug or placebo, each administered once every 3 weeks for a total of 5 IV infusions. Efficacy, treatment-emergent adverse events (AEs), and mean change from baseline (CFB) in GO-QOL scores (exploratory endpoint) were assessed through Week 15.

Results:

A total of 113 patients received veligrotug (n=75) or placebo (n=38). Veligrotug resulted in improvements in TED signs/symptoms as early as Week 3, with statistically significant improvements vs placebo at Week 15 for all primary and secondary outcomes (p<0.0001 for all) including: overall responder rate by Hertel (67% vs 5%), proptosis responder rate by Hertel (70% vs 5%), mean CAS reduction (3.4 vs 1.7), diplopia response (63% vs 20%), and diplopia resolution (54% vs 12%). These significant improvements translated into rapid and clinically meaningful improvements in GO-QOL, exceeding the minimal clinically important difference (8 points) over baseline at Week 15 for veligrotug vs placebo. The GO-QOL overall score mean CFB was 17.3 vs 2.9, with 16.5 vs 2.3 for the visual functioning subscale and 18.1 vs 3.6 for the appearance subscale (nominal p<0.001 for all). Most AEs were mild and there were no treatment-related serious AEs.  

Conclusions:

Veligrotug was generally well tolerated and led to rapid and statistically significant improvements in proptosis, CAS, and diplopia, and clinically meaningful improvement in quality-of-life outcomes in patients with active TED. A 12-week, 5-infusion treatment regimen of veligrotug may become a potential treatment option for TED.