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Veligrotug Achieves 70% Proptosis Response Rate Versus 5% With Placebo in Active Thyroid Eye Disease
In a phase 3 placebo-controlled trial, veligrotug — an anti-IGF-1R monoclonal antibody — produced a proptosis responder rate of 70% compared with 5% for placebo at week 15 (p < 0.001), with an overall responder rate of 67% versus 5% (p < 0.001). Responses were evident as early as week 3 and were maintained through week 52 in 70% of initial responders, supporting both a rapid onset and durable therapeutic effect.
What Was Studied
The THRIVE trial investigated whether veligrotug, a full antagonist monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), could meaningfully reduce proptosis and disease activity in patients with moderate-to-severe active thyroid eye disease (TED). The primary outcomes assessed at week 15 were the proptosis responder rate — defined as a reduction of at least 2 mm by Hertel exophthalmometry — and, in certain geographic regions, an overall responder rate that additionally required a minimum 2-point reduction in the clinical activity score (CAS).
How It Was Studied
THRIVE was a global, multicenter, randomized, double-masked, placebo-controlled phase 3 trial in which 113 adult patients with moderate-to-severe active TED were enrolled. Eligible patients had disease onset within 15 months, proptosis at least 3 mm above normal, and a CAS of 3 or higher. Participants were randomized 2:1 to receive either veligrotug at 10 mg/kg intravenously or matching placebo, administered every 3 weeks for a total of 5 infusions over 12 weeks. Efficacy and safety were evaluated through week 52, providing both a near-term and longer-term view of the treatment’s profile. The placebo arm comprised 38 patients and the veligrotug arm 75 patients, with baseline characteristics reported as balanced between the two groups.
What Was Observed
- Proptosis response at week 15 was dramatically higher with veligrotug than placebo. Seventy percent of veligrotug-treated patients achieved a clinically meaningful reduction in proptosis of at least 2 mm by Hertel exophthalmometry, compared with only 5% in the placebo group (p < 0.001). This large absolute difference of 65 percentage points was corroborated by imaging: 71% versus 9% achieved the same threshold when proptosis was measured by MRI or CT.
- Mean proptosis reduction was approximately six times greater with veligrotug. Across the treatment group, eye protrusion decreased by a mean of 2.90 mm by Hertel measurement and 2.96 mm by MRI or CT imaging, compared with 0.48 mm and 0.58 mm, respectively, in the placebo group — consistent reductions confirmed across two independent measurement modalities.
- Diplopia outcomes also favored veligrotug substantially. Among patients with pre-existing diplopia, 59% in the veligrotug arm showed improvement compared with 20% in the placebo arm; complete resolution of diplopia was achieved in 49% of veligrotug-treated patients versus 12% of those receiving placebo — a clinically meaningful difference in one of the most functionally disruptive manifestations of TED.
- Durable responses were observed through one year, and the safety profile was favorable. At week 52, 70% of initial proptosis responders maintained their response. The treatment discontinuation rate was 4%, most adverse events were mild and self-limiting, and no serious treatment-related adverse events were reported. The safety profile remained stable from the end of dosing through the end of the observation period.
Why This Matters
TED is characterized as a debilitating autoimmune disease with significant unmet treatment needs, and the THRIVE trial provides evidence that targeting the IGF-1R pathway with a full receptor antagonist can produce rapid, substantial, and sustained reductions in the cardinal features of active disease — proptosis, diplopia, and clinical activity. The 5-infusion regimen over 12 weeks, combined with response durability through week 52, suggests a potentially practical and time-limited dosing course. If corroborated in broader clinical use, veligrotug could represent a new mechanistic approach to TED management alongside existing options.
How to Read This Result
While the effect sizes observed in THRIVE are large and statistically compelling across multiple endpoints, the relatively small overall sample size of 113 patients, limited subgroup data, and the use of geographically variable primary endpoints introduce residual uncertainty that warrants confirmation in larger and more diverse study populations before the full benefit-risk profile can be considered definitively established.
Limitations
The abstract does not explicitly report study limitations.