A Review on the Pharmacology and Therapeutic Applications of Veligrotug-vvze for the Treatment of Thyroid Eye Disease

Review Article

Abstract

Thyroid eye disease is a debilitating autoimmune disorder of the orbit characterized by soft-tissue expansion, proptosis, diplopia, and progressive tissue remodeling. The pathogenesis is driven by an autoimmune interaction involving the insulin-like growth factor-1 receptor and thyroid-stimulating hormone receptor complex on orbital fibroblasts, initiating intracellular signaling cascades that promote hyaluronan accumulation, adipogenesis, and interstitial edema. Traditional interventions, consisting primarily of high-dose systemic corticosteroids, external orbital irradiation, and rehabilitative surgical decompression, show variable clinical responses and frequently fail to alter underlying tissue expansion or long-term fibrotic sequelae. Veligrotug-vvze is a targeted humanized immunoglobulin G1 kappa monoclonal antibody designed as a full antagonist of the insulin-like growth factor-1 receptor. Through selective receptor occupancy, veligrotug-vvze blocks ligand autophosphorylation and disrupts downstream phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase signaling cascades, terminating fibroblast differentiation and extracellular matrix expansion. The clinical development program, evaluated across pivotal phase III clinical trials including THRIVE and THRIVE-2, established therapeutic efficacy across both active and chronic disease states. Administered as a condensed regimen of five intravenous infusions at three-week intervals, veligrotug-vvze achieves clinically meaningful reductions in proptosis, improvements in diplopia, and attenuation of inflammatory indices. Adverse events require clinical vigilance, particularly regarding glycemic control, otologic monitoring for auditory disturbances, and screening for inflammatory bowel disease. Veligrotug-vvze is a refined, targeted biological paradigm that alters orbital tissue dynamics across distinct stages of thyroid eye disease