OR31-07 THRIVE-2 Phase 3 Trial of Veligrotug (VRDN-001) in Chronic Thyroid Eye Disease (TED): Efficacy and Safety at 15 Weeks

Abstract Disclosure: A. Patel Jain: Viridian Therapeutics, Inc., Amgen Inc. K. Cockerham: Viridian Therapeutics, Inc., Amgen Inc, Lassen Therapeutics LLC, Roche Pharmaceuticals, Immunovant, Tourmaline. J. Abrams: Viridian Therapeutics, Inc., Amgen Inc. J. Mandeville: Viridian Therapeutics, Inc. M. Al Khudari: Viridian Therapeutics, Inc. S. Leibowitz: Viridian Therapeutics, Inc., Amgen Inc, Lassen Therapeutics LLC. D. Lemor: Viridian Therapeutics, Inc. R.E. Turbin: Viridian Therapeutics, Inc., Amgen Inc, Medtronic. R.E. Turbin: Viridian Therapeutics, Inc., Amgen Inc, Medtronic. A. Kossler: Viridian Therapeutics, Inc., Amgen Inc, Sling Therapeutics, Lassen Therapeutics LLC, Immunovant, Genentech, Inc., Argenx, Acelyrin. W. Conroy: Viridian Therapeutics, Inc. A. Narvekar: Viridian Therapeutics, Inc. T.A. Ciulla: Viridian Therapeutics, Inc. R. Tang: Viridian Therapeutics, Inc., Amgen Inc, Alexion Pharmaceuticals, Inc., EMD Serono. Introduction: TED remains a condition with significant unmet needs, particularly in the chronic phase, where treatment options are limited. IGF-1R antagonism has emerged as a key therapeutic approach, addressing inflammation and proptosis. Veligrotug (veli), a full antagonist humanized monoclonal antibody targeting IGF-1R, previously demonstrated positive results in the ongoing phase 3 THRIVE trial for active TED. Here, we present efficacy and safety data from the ongoing phase 3 THRIVE-2 trial (NCT06021054) of veli in chronic TED at the primary timepoint of 15 weeks. Methods: Adults with moderate-to-severe chronic TED (onset >15 months, proptosis ≥3 mm, with any clinical activity score [CAS]) were randomized (2:1) to 5 IV infusions 3 weeks apart of either 10 mg/kg veli or placebo. The following were assessed through 15 weeks: proptosis responder rate (PRR), defined as ≥2-mm reduction vs baseline by Hertel exophthalmometry; overall responder rate (ORR; PRR and no worsening in CAS); PRR by MRI/CT; mean change from baseline in proptosis; Gorman diplopia responder rate (DRR) and complete resolution; and treatment-emergent adverse events (TEAEs). Results: 188 patients were randomized to veli (n=125) or placebo (n=63) and included in the intent-to-treat population. Baseline values for veli vs placebo were balanced including mean proptosis, 24.3 mm vs 23.8 mm; presence of diplopia, 52% vs 59%; CAS ≥3, 57% vs 52%. 15-week results for veli vs placebo were as follows: Hertel PRR, 56% vs 8% (p<0.0001), with a mean reduction of 2.34 mm vs 0.46 mm (p<0.0001); MRI/CT PRR, 48% vs 3% (p<0.0001); ORR, 56% vs 7% (p<0.0001). In patients with diplopia at baseline, DRR was 56% vs 25% (p=0.0006); complete resolution occurred in 32% vs 14% (p=0.0152). In patients with CAS ≥3 at baseline, CAS 0/1 (exploratory endpoint) was achieved in 54% vs 24% (nominal p=0.0060). Most TEAEs were mild, with most common being muscle spasms (36% vs 6%) and menstrual disorders (33% vs 10% for menstruating women). Hearing impairment was 13% vs 3%. Serious TEAEs were 2% vs 3% (1 related to treatment in each group). Conclusions: THRIVE-2, which assessed 5 IV infusions of veli vs placebo, is the first RCT in chronic TED to show statistically significant improvement not only in proptosis, but also in subjective diplopia, with a generally well-tolerated safety profile. Results suggest the promising potential of veli in chronic TED. Follow-up through 52 weeks is ongoing. Presentation: Monday, July 14, 2025