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TOPLINE:

Veligrotug, a full antagonist monoclonal antibody targeting the insulin-like growth factor‑1 receptor, administered as five intravenous (IV) infusions over 12 weeks, demonstrated rapid and durable improvements in proptosis, diplopia, and disease activity in patients with moderate-to-severe active thyroid eye disease (TED). Most patients who had reduced proptosis at week 15 maintained that improvement through week 52. 

METHODOLOGY:

• Researchers conducted THRIVE, a global, multicenter, phase 3 trial across 29 sites in North America, Europe, and Australia to evaluate the efficacy and safety of veligrotug in patients with moderate-to-severe active TED.
• A total of 113 adult patients with moderate-to-severe active TED — with disease onset within 15 months, proptosis at least 3 mm above normal, and a clinical activity score of 3 or more — were randomly assigned to receive either 10 mg/kg of veligrotug (n = 75) or placebo (n = 38), delivered as five IV infusions every 3 weeks over a 12-week period.
• Primary endpoints varied by region and were assessed at week 15: In North America, the primary endpoint was the proptosis responder rate (reduction of ≥ 2 mm in proptosis in the study eye without a ≥ 2 mm increase in the fellow eye). In Europe and Australia, the primary endpoint was the overall responder rate (proptosis responder criteria and having a reduction of two points or more in the clinical activity score in the study eye without an increase of two points or more in the fellow eye).
• Proptosis was measured using standardized ophthalmologic tests (Hertel exophthalmometry) and MRI or CT scans.
• Efficacy and safety were assessed through week 52; the durability of proptosis response was analyzed only in patients who responded at week 15 and had follow-up data at week 52.

TAKEAWAY:

• At week 15, use of veligrotug was associated with a significantly greater response than placebo in the proptosis responder rate by Hertel exophthalmometry (70% vs 5%; P < .001) and by MRI/CT (71% vs 9%; P < .001), as well as in the overall responder rate (67% vs 5%; P < .001); among initial proptosis responders who had data at week 52, 70% maintained their response.
• By week 15, among patients who had diplopia at baseline, 59% of those treated with veligrotug showed improvement, and 49% had complete resolution vs 20% improvement and 12% resolution with placebo; disease inactivation, defined as a clinical activity score of 0 or 1, was achieved in 65% of patients receiving veligrotug vs 18% receiving placebo.
• Rapid improvements across multiple endpoints appeared as early as week 3 after the first infusion, and the median time to proptosis response with veligrotug was 3.5 weeks.
• Veligrotug was generally well tolerated, with a 4% treatment discontinuation rate and no serious treatment-related adverse events; most adverse events were mild and transient.

IN PRACTICE:

“These results support veligrotug’s potential to advance TED management by offering a next-generation therapy that targets the underlying pathophysiologic features and its clinical manifestations,” the researchers reported.

SOURCE:

The study was led by Michael T. Yen, MD, of the Alkek Eye Center at Baylor College of Medicine in Houston. It was published online on June 1, 2026, in Ophthalmology.

LIMITATIONS:

The Gorman score used to assess diplopia is a subjective, patient-reported measure. The study assessed patients through week 52, but longer-term follow-up is needed to determine how long those benefits persist. A separate study is needed to assess the role of veligrotug in chronic TED, as the current study focused on active disease.

DISCLOSURES:

Viridian Therapeutics, Inc., funded the study. Three authors declared being equity owners and employees of the funding agency. Many other authors received consulting fees, advisory or lecture payments, research support, and other ties with Viridian Therapeutics and other companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.