Purpose

Veligrotug, an investigational full antagonist monoclonal antibody to IGF-1R, demonstrated statistically significant improvements in key TED domains in two phase 3 trials: THRIVE (NCT05176639, active TED) and THRIVE-2 (NCT06021054, chronic TED). This subgroup analysis assessed the robustness of veligrotug’s treatment effect across the spectrum of TED duration, baseline proptosis, and clinical activity.

---

Methods

Adults with moderate-to-severe TED were randomized to 5 IV infusions of veligrotug 10 mg/kg or placebo each administered once Q3W in THRIVE (active TED, onset ≤15 months, clinical activity score [CAS] ≥3) or THRIVE-2 (chronic TED, onset >15 months, any CAS). A key secondary efficacy endpoint in Europe was the proptosis responder rate at Week 15 (PRR, ≥2-mm reduction from baseline in the study eye without a ≥2-mm increase in the fellow eye), assessed by Hertel exophthalmometry. Subgroup analyses assessed treatment effect compared to placebo by TED duration, clinical activity, baseline proptosis, gender, age, and tobacco use.

---

Results

A total of 301 patients were randomized across THRIVE (75 veligrotug vs 38 placebo) and THRIVE-2 (125 veligrotug vs 63 placebo). Veligrotug met the primary and all key secondary endpoints in both studies at Week 15. PRR was significantly higher for veligrotug vs placebo in THRIVE (70% vs 5%, p<0.0001) and THRIVE-2 (56% vs 8%, p<0.0001) in the overall population, with consistently greater PRR for veligrotug than placebo across all evaluated subgroups in each study (nominal p<0.01). Discontinuation rates in the veligrotug arms were low (4% in THRIVE; 6% in THRIVE-2), and most AEs were mild.

---

Conclusion

Veligrotug has been evaluated in the largest phase 3 clinical program of IGF-1R inhibition in TED to date. A 12-week 5-infusion course of veligrotug was generally well tolerated and led to a significant treatment effect in both active and chronic TED across the spectrum of disease duration and baseline characteristics, including proptosis and clinical activity. Veligrotug may become a promising new treatment option for TED.

---

Additional Authors

First name	Last name	Base Hospital / Institution
Antonio Manuel	Garrido-Hermosilla	Hospital Universitario Virgen Macarena, Universidad de Sevilla
Michael	Schittkowski	Universitätsmedizin Göttingen
Vickie	Lee	Imperial College Healthcare NHS Trust – Western Eye Hospital
Edwina	Eade	University of Sydney, New South Wales, Australia
Marta	Pérez-López	Hospital Universitario y Politécnico La Fe, Valencia, Spain
Patrice	Rodien	Centre Hospitalier Universitaire d’Angers, Dept. of Endocrinology
Will	Conroy	Viridian Therapeutics, Inc.
Abhijit	Narvekar	Viridian Therapeutics, Inc.

↑ Back to top