THRIVE-2 Phase 3 Study in Chronic Thyroid Eye Disease (TED): 15-Week Efficacy and Safety Results of Veligrotug (VRDN-001), a Full Antagonist Humanized Monoclonal Antibody to IGF-1 Receptor
Author: Anja Eckstein
Base Hospital / Institution: University Duisburg Essen
Rapid fire oral presentation
Abstract ID: 25-286
Purpose
Clinical and preclinical evidence indicate a central role for IGF-1R antagonism in reducing TED-related inflammation and proptosis. Veligrotug is being assessed in 2 ongoing phase 3 RCTs, THRIVE (active TED) and THRIVE-2 (chronic TED). Here we present 15-week efficacy and safety results from THRIVE-2 (NCT06021054).
Methods
Adults with moderate-to-severe chronic TED (onset >15 months, proptosis ≥3 mm, and any clinical activity score [CAS]) were randomized to 5 IV infusions Q3W of 10 mg/kg veligrotug or placebo. Efficacy outcomes and treatment-emergent AEs were assessed through 15 weeks (primary timepoint).
Results
188 patients received veligrotug (n=125) or placebo (n=63). Baseline (BL) values for veligrotug vs placebo were balanced, including diplopia in 52% vs 59% and CAS ≥3 in 57% vs 52%. Veligrotug improved TED symptoms as early as 3 weeks after first infusion. 15-week results for veligrotug vs placebo were as follows: overall responder rate (proptosis responder rate [PRR], ≥2-mm reduction vs BL by MRI/CT and no worsening of CAS vs BL), 48% vs 3% (p<0.0001); PRR by MRI/CT, 48% vs 3% (p<0.0001), with a mean reduction of 2.07 mm vs 0.36 mm; PRR by Hertel exophthalmometry, 56% vs 8% (p<0.0001), with a mean reduction of 2.34 mm vs 0.46 mm (p<0.0001). In patients reporting diplopia on the Gorman subjective diplopia scale at BL, improvement was reported in 56% vs 25% (p=0.0006) and complete resolution in 32% vs 14% (p=0.0152) at 15 weeks. Exploratory analysis was nominally significant for achievement of CAS 0/1 at 15 weeks in patients with CAS ≥3 at BL (54% vs 24%; p=0.0060). Most AEs were mild; most common was muscle spasms (36% vs 6%). Hearing impairment AEs occurred in 13% vs 3% and serious AEs in 2% vs 3% (1 per treatment-related/group).
Conclusion
The THRIVE-2 study of veligrotug in chronic TED clearly shows disease duration is not a limiting parameter. A 5-dose treatment regimen led to rapid and significant improvements not only in proptosis but also in diplopia, with a generally well-tolerated safety profile. Follow-up through 52 weeks is ongoing, with future analyses and studies aiming to support optimal patient selection.
Additional Authors
| First name | Last name | Base Hospital / Institution |
|---|---|---|
| Antonio Manuel Garrido | Hermosilla | Hospital Universitario Virgen Macarena |
| Michael | Schittkowski | Universitätsmedizin Göttingen |
| Onur | Konuk | Gazi University Medical School, Dept. of Ophthalmology, Ankara |
| Adrienne | Csutak | Dept. of Ophthalmology, University of Pécs Medical School |
| Edwina | Eade | University of Sydney |
| Patrice | Rodien | Centre Hospitalier Universitaire d’Angers, Dept. of Endocrinology |
| Jimmy | Uddin | Moorsfields Eye Hospital London |
| Vickie | Lee | Imperial College Healthcare NHS Trust – Western Eye Hospital, London |
| Marco | Sales Sanz | Hospital Universitario Ramón y Cajal, Madrid |
| Will | Conroy | Viridian Therapeutics, Inc., Waltham, MA, USA |
| Abhijit | Narvekar | Viridian Therapeutics, Inc., Waltham, MA, USA |
| on behalf of THRIVE-2 Study Group |
