Novel Biologics Including FcRn Inhibitors and IGF-1R Blockers Transforming Treatment of Graves' Ophthalmopathy
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A 2025 review of the rapidly expanding pharmacological landscape for Graves' ophthalmopathy highlights how new biologics, including teprotumumab, batoclimab, and IGF-1R inhibitors, are dramatically improving outcomes for patients with thyroid eye disease. These agents target the underlying immune pathways driving orbital inflammation and proptosis rather than merely managing symptoms. For patients who previously had few treatment options beyond steroids and surgery, this new class of drugs represents a major shift in what is possible for preserving vision and quality of life.
Abstract
Graves' ophthalmopathy (GO), also known as thyroid eye disease (TED), is the most common extrathyroidal manifestation of Graves' disease, causing orbital inflammation, expansion of extraocular muscles, proptosis, diplopia, and in severe cases, compressive optic neuropathy with vision loss. For decades, treatment was largely limited to intravenous glucocorticoids, orbital decompression surgery, and radiation, with limited efficacy in the chronic phase.
This review summarizes recent advances in the pharmacological treatment of active GO, focusing on novel immunomodulators and biological agents. Teprotumumab, an anti-IGF-1R monoclonal antibody approved by the FDA in 2020, has revolutionized the management of moderate-to-severe active TED by demonstrating significant proptosis reduction and functional improvement in phase 3 trials. FcRn inhibitors such as batoclimab reduce circulating pathogenic IgG levels including TRAb and total IgG, and have shown marked antibody reduction in proof-of-concept trials, with multicenter phase 3 studies ongoing.
Emerging investigational agents include veligrotug, lonigutamab, and VRDN-003, all targeting IGF-1R through subcutaneous or intravenous routes, with multiple phase 3 trials reporting or pending results. Additional approaches including anti-CD20 therapy with rituximab, tocilizumab targeting IL-6, and novel oral agents also show activity in active GO. The authors identify active inflammatory disease, TSH receptor antibody status, and prior steroid response as key factors for optimal treatment selection among available and emerging options.