Veligrotug in Active Thyroid Eye Disease: THRIVE Phase 3 Trial

Key Takeaways

• Week 15 primary and secondary outcomes favored veligrotug over placebo, with reported comparisons meeting P < 0.001.
• Improvement was observed by week 3, and 70% of initial responders maintained proptosis response at week 52.
• Treatment was generally well tolerated, discontinuation occurred in 4% of patients, and no serious treatment-related adverse events were reported.

Veligrotug produced a week 15 proptosis responder rate of 70% compared with 5% for placebo in adults with active thyroid eye disease in the THRIVE phase 3 trial. The insulin-like growth factor-1 receptor antagonist antibody was evaluated in adults with moderate-to-severe active disease in a global, multicenter, randomized, double-masked, placebo-controlled study. A total of 113 patients received treatment during the randomized study period, and efficacy and safety were assessed through week 52, extending follow-up beyond the primary week 15 comparison.

Enrollment was limited to adults with moderate-to-severe active thyroid eye disease with disease onset within 15 months. Eligible participants also needed proptosis of at least 3 mm above normal and a clinical activity score of at least 3. Patients were randomized 2:1 to veligrotug or placebo, and baseline characteristics were balanced between groups. Veligrotug was given at 10 mg/kg every 3 weeks for a total of 5 IV infusions, described as 5 infusions over 12 weeks before the prespecified week 15 efficacy assessment.

The prespecified week 15 endpoint was the proptosis responder rate or overall responder rate, depending on geographic region. Among the 113 treated patients, 75 were assigned to veligrotug and 38 to placebo. Proptosis responder rates at week 15 were 70% versus 5% by Hertel and 71% versus 9% by MRI or CT, while the overall responder rate was 67% versus 5%. Mean proptosis reduction was 2.90 mm versus 0.48 mm by Hertel and 2.96 mm versus 0.58 mm by MRI or CT. Diplopia improvement was 59% versus 20%, and diplopia resolution was 49% versus 12%, with all reported week 15 primary and secondary comparisons favoring veligrotug at P < 0.001.

Improvement was observed as early as week 3, indicating measurable activity before the primary week 15 analysis. At week 52, 70% of initial responders maintained proptosis response through follow-up. Veligrotug was generally well tolerated, and treatment discontinuation occurred in 4% of patients during the study. Most adverse events were mild and resolved, with no serious treatment-related adverse events and no change in the safety profile through week 52.

The authors concluded that veligrotug may become a promising new treatment option, and the follow-up findings described durable response without a new safety signal.