Introduction: Primary results from the ongoing Phase 3 THRIVE study (NCT05176639) in active Thyroid Orbitopathy (TO) showed that veligrotug (veli) resulted in rapid onset and significant improvement of TO symptoms. Here, we focus on the primary results of veli in chronic TO from the ongoing THRIVE-2 study (NCT06021054).

Methods: In THRIVE-2, adults with moderate-to-severe chronic OT (onset > 15 months and any clinical activity score [CAS]) were randomly assigned to receive five IV infusions every 3 weeks of 10 mg/kg veli or placebo (pbo). Efficacy outcomes and treatment AEs were assessed through 15 weeks.

Results: 188 patients received Veli (n = 125) or Pbo (n = 63), with balanced baseline values. Veli improved symptoms from week 3. At week 15, the overall response rate (reduction in proptosis #1 2 mm by MRI/CT and absence of worsening of TO from baseline) was 48 vs. 3% (p < 0.0001). In patients who reported diplopia on the Gorman Subjective Diplopia Scale at baseline, improvement was observed in 56 vs. 25% (p = 0.0006) and complete resolution in 32 vs. 14% (p = 0.0152) at 15 weeks. Most AEs were mild; the most common was muscle spasms (36 vs. 6%). There were auditory AEs in 13 vs. 3% and severe AEs in 2 vs. 3% (1 related by MRI/CT and no worsening of OT compared to baseline).

Conclusions: Veli was generally well tolerated and produced a statistically significant treatment effect across all primary and secondary endpoints in both THRIVE and THRIVE-2. With a 5-dose treatment regimen, rapid onset, and an effect on diplopia, Veli may represent a promising new treatment for both active and chronic TO. Follow-up is ongoing for up to 52 weeks.

Presentado en el Congreso COPHy 2025.