THRIVE Phase 3 Study in Active Thyroid Eye Disease (TED): 15-Week Efficacy and Safety of Veligrotug (VRDN-001), a Full Antagonist Humanized Monoclonal Antibody to IGF-1 Receptor
Author: Antonio Manuel Garrido Hermosilla
Base Hospital / Institution: Andalusian Referral Unit for Thyroid Eye Disease (Andalusian Public Health System), Oculoplastics-Orbit and Ocular Oncology Units, Department of Ophthalmology, Virgen Macarena University Hospital. Associate Professor of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Seville, Seville, Spain
Rapid fire oral presentation
Abstract ID: 25-242
Purpose
Clinical and preclinical evidence indicate a central role for IGF-1R receptor (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 efficacy and safety of veligrotug at 15 weeks from THRIVE (NCT05176639).
Methods
Adults with moderate-to-severe active TED (onset ≤15 months, proptosis ≥3 mm, and clinical activity score [CAS] ≥3) were randomized to 5 IV infusions Q3W of 10 mg/kg veligrotug or placebo. Efficacy outcomes and treatment-emergent adverse events (AEs) were assessed through 15 weeks (primary timepoint).
Results
113 patients received veligrotug (n=75) or placebo (n=38). Baseline (BL) values for veligrotug vs placebo were balanced, including mean proptosis of 23.2 mm in each group, mean CAS of 4.5 vs 4.8, and diplopia in 67% vs 68%. 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 Hertel exophthalmometry and ≥2-point improvement in CAS vs BL), 67% vs 5% (p<0.0001); PRR by Hertel, 70% vs 5% (p<0.0001), with a mean reduction of 2.9 mm vs 0.5 mm (p<0.0001); PRR by MRI/CT, 69% vs 9% (p<0.0001), with a mean reduction of 2.9 mm vs 0.6 mm (p<0.0001); and mean CAS decrease, 3.4 vs 1.7 (p<0.0001). In patients reporting diplopia on the Gorman subjective diplopia scale at BL, improvement was reported in 63% vs 20% (p<0.0001) and complete resolution in 54% vs 12% (p<0.0001) at 15 weeks. Most AEs were mild; most common was muscle spasms (43% vs 5%). Hearing impairment AEs occurred in 16% vs 11% and serious AEs in 4 patients (veligrotug, all unrelated to treatment).
Conclusion
Primary results from THRIVE in active TED show 5 IV infusions of 10 mg/kg veligrotug were generally well tolerated, with rapid onset and significant and clinically meaningful improvements in proptosis, diplopia, and CAS. Results suggest the promising potential of veligrotug in active TED. Additional follow-up through 52 weeks is ongoing.
Additional Authors
| First name | Last name | Base Hospital / Institution |
|---|---|---|
| Michael | Schittkowski | Universitätsmedizin Göttingen, Göttingen, Germany |
| Vickie | Lee | Imperial College Healthcare NHS Trust – Western Eye Hospital, London, United Kingdom |
| Julian | Bermúdez Pío-Rendón | Metavisión Arruzafa (Hospital La Arruzafa), Cordoba, Spain |
| Eckart | Bertelmann | Department of Ophthalmology, Charité University Medicine Berlin, Berlin, Germany |
| Edwina | Eade | North Shore Private Hospital, New South Wales, Australia |
| Marta | Pérez-López | Hospital Universitario Y Politécnico La Fe, Valencia, Spain |
| Marco | Sales Sanz | Hospital Universitario Ramón y Cajal, Madrid, Spain |
| Patrice | Rodien | Centre Hospitalier Universitaire d’Angers, Dept. of Endocrinology, Angers, France |
| Ashley | Pajak | Viridian Therapeutics, Inc., Waltham, MA, USA |
| Abhijit | Narvekar | Viridian Therapeutics, Inc., Waltham, MA, USA |
| Peerooz | Saeed | Amsterdam UMC location AMC, Amsterdam, The Netherlands |
| THRIVE Study Group |
