As reported on Medscape, global phase 3 clinical trial suggests that veligrotug, an investigational monoclonal antibody targeting the insulin-like growth factor‑1 receptor (IGF‑1R), may offer fast and lasting improvement for patients with moderate-to-severe active thyroid eye disease (TED). Administered as five intravenous infusions over a 12-week course, the therapy demonstrated meaningful reductions in proptosis, improvements in diplopia, and decreased disease activity, with many benefits persisting up to one year.
Study Design and Patient Population
The THRIVE trial was conducted across 29 centers spanning North America, Europe, and Australia. Investigators enrolled 113 adults with active TED of relatively recent onset (within 15 months), all of whom had clinically significant orbital involvement, including proptosis of at least 3 mm above normal and a clinical activity score (CAS) of 3 or higher.
Participants were randomized to receive either veligrotug at a dose of 10 mg/kg (75 patients) or placebo (38 patients). Treatment was delivered in five infusions spaced three weeks apart. The primary efficacy endpoint at 15 weeks differed slightly by geographic region: North American sites focused on reduction in proptosis, while European and Australian sites used a composite endpoint that combined proptosis improvement with reductions in inflammation as measured by CAS.
Rapid and Robust Clinical Response
By week 15, veligrotug demonstrated clear superiority over placebo across multiple measures. Approximately 70% of treated patients achieved a clinically meaningful reduction in proptosis, compared with only single-digit response rates in the placebo group. Imaging-based assessments using MRI or CT reinforced these findings, showing similarly strong differences between groups.
When broader response criteria were applied—including both structural improvement and reduced inflammatory activity—about two-thirds of patients receiving veligrotug met response thresholds, versus a small minority of placebo recipients.
Notably, clinical improvement was observed early in the treatment course. Some patients began to show benefit as soon as three weeks after the first infusion, with a median time to proptosis response of just over three weeks.
Impact on Diplopia and Disease Activity
Beyond proptosis, veligrotug also produced meaningful gains in other key manifestations of TED. Among patients experiencing diplopia at the start of the study, more than half showed improvement with treatment, and nearly half achieved complete resolution. This contrasted with substantially lower rates of improvement in the placebo cohort.
Disease activity also declined significantly. By week 15, nearly two-thirds of treated patients reached inactive disease status (defined as a CAS of 0 or 1), compared with fewer than one in five individuals receiving placebo.
Durability of Benefit
Follow-up data through week 52 indicated that the therapeutic effects were largely sustained. Among patients who had initial improvement in proptosis and remained in follow-up, about 70% maintained their response one year after starting therapy. This durability is especially relevant given the often chronic and relapsing nature of TED.
Safety Profile
Veligrotug was generally well tolerated. Only a small proportion of participants discontinued treatment due to adverse effects, and no serious safety signals attributed to the drug were observed. Reported side effects were typically mild and transient.
Clinical Implications
The findings from THRIVE point to veligrotug as a promising next-generation therapy for TED, targeting a key receptor involved in disease pathophysiology. Its rapid onset of action, combined with sustained efficacy across multiple clinical domains, may position it as a valuable addition to current treatment options.
The study was led by Dr. Michael T. Yen of Baylor College of Medicine and published online in Ophthalmology on June 1, 2026.
