OR31-04 Efficacy and Safety of Veligrotug (VRDN-001), a Full Antagonist Monoclonal Antibody to IGF-1 Receptor, in Active Thyroid Eye Disease (TED): THRIVE Phase 3 Topline Results

Abstract Disclosure: R. Mudumbai: Viridian Therapeutics, Inc., Nicox Ophthalmics, Stoke Pharmaceuticals. S. Leibowitz: Viridian Therapeutics, Inc., Lassen Therapeutics LLC, Amgen. Y. Michael T.: Viridian Therapeutics, Inc., Ipsen Innovations, Sling Therapeutics. K. Cockerham: Viridian Therapeutics, Inc., Horizon Therapeutics, Immunovant, Lassen Therapeutics LLC, Tourmaline, Roche. J. Abrams: Viridian Therapeutics, Inc., Horizon Therapeutics. R.E. Turbin: Viridian Therapeutics, Inc., Horizon Therapeutics, Medtronic. N. Nijhawan: Viridian Therapeutics, Inc. S. Zhang-Nunes: Viridian Therapeutics, Inc., Amgen, Tarsus. A. Kossler: Viridian Therapeutics, Inc., Horizon Therapeutics, Sling Therapeutics, Lassen Therapeutics LLC, Immunovant, Genetech, Argenx, Acelyrin. C. Michalsky: Viridian Therapeutics, Inc. A. Narvekar: Viridian Therapeutics, Inc. T. Ciulla: Viridian Therapeutics, Inc.. Introduction: Veligrotug, a full antagonist humanized monoclonal antibody to the IGF-1 receptor (IGF-1R), is an investigational treatment for thyroid eye disease (TED). Clinical and preclinical evidence indicate a central role for IGF-1R antagonism in reducing the inflammation and proptosis that occur in TED. We assessed topline efficacy and safety results at 15 weeks from an ongoing phase 3 randomized double-masked placebo-controlled trial of veligrotug vs placebo in patients with active TED (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 3 weeks apart of either 10 mg/kg veligrotug or placebo. The primary endpoint in North America (proptosis responder rate [PRR], defined as ≥2-mm reduction vs baseline by Hertel exophthalmometry), PRR by MRI/CT, complete resolution of diplopia, mean changes from baseline in proptosis and CAS, and treatment-emergent adverse events (AEs) were assessed through 15 weeks, with follow-up ongoing through 52 weeks. Results: A total of 113 patients were randomized to veligrotug (n=75) or placebo (n=38) and included in the intention-to-treat population. At baseline, mean proptosis was 23.2 mm in each group; CAS was 4.5 vs 4.8 and diplopia was present in 67% vs 68% of patients for veligrotug vs placebo. At 15 weeks, PRR by Hertel was 70% vs 5% (p<0.0001) for veligrotug vs placebo, with a mean reduction of 2.9 mm vs 0.5 mm (p<0.0001). PRR by MRI/CT was 69% vs 9% (p<0.0001) for veligrotug vs placebo, with a mean reduction of 2.9 mm vs 0.6 mm (p<0.0001). Mean CAS decreased by 3.4 vs 1.7 (p<0.0001) for veligrotug vs placebo. In patients with diplopia, complete resolution of diplopia occurred in 54% (27/50) vs 12% (3/26) (p<0.0001) for veligrotug vs placebo. AEs occurred for 66 (88%) veligrotug vs 24 (63%) placebo patients, and most were mild; 4 patients (veligrotug) had serious AEs (all unrelated to treatment). Hearing impairment AEs were reported for 12 (16%) veligrotug vs 4 (11%) placebo patients. Conclusions: Topline results from the THRIVE phase 3 trial show 5 IV infusions of 10 mg/kg veligrotug were well tolerated and led to significant and clinically meaningful improvements in proptosis, CAS, and diplopia at 15 weeks. Additional follow-up through 52 weeks is ongoing. Presentation: Monday, July 14, 2025