Viridian Therapeutics has announced positive topline results from its Phase 3 THRIVE clinical trial, evaluating veligrotug (VRDN-001), an intravenously delivered anti-insulin-like growth factor-1 receptor (IGF-1R) antibody, for the treatment of active thyroid eye disease (TED). The study demonstrated statistically significant and clinically meaningful improvements across key disease endpoints at 15 weeks.
THRIVE Trial Results
The THRIVE trial (NCT05176639) enrolled 113 patients, with 75 receiving veligrotug and 38 receiving placebo. The study met both primary and all secondary endpoints at 15 weeks following five infusions of veligrotug. Notably, a rapid onset of action was observed, with 53% of veligrotug-treated patients achieving a proptosis response after just one infusion (3 weeks after therapy initiation).
Key findings include:
- Proptosis Responder Rate (PRR): 70% in the veligrotug group versus 5% in the placebo group (p < 0.0001), representing a 64% placebo-adjusted PRR.
- Proptosis Reduction: A mean reduction of 2.9 mm from baseline in the veligrotug group compared to a 0.5 mm reduction in the placebo group.
- Diplopia Resolution: Complete resolution in 54% of patients receiving veligrotug versus 12% receiving placebo. The diplopia response rate was 63% in the veligrotug group and 20% in the placebo group.
- Overall Response: 67% in the veligrotug group versus 5% in the placebo group.
Safety and Tolerability
Veligrotug was generally well-tolerated, with most adverse events (AEs) being mild. The discontinuation rate in the veligrotug arm was low (4%), and no treatment-related serious AEs were reported. Hearing impairment was observed in 16% of patients receiving veligrotug, compared to 10.5% in the placebo group.
Expert Commentary
Michael Yen, MD, an investigator in THRIVE and Professor of Oculoplastic Surgery and Ophthalmology at Baylor College of Medicine, noted the favorable safety profile of veligrotug, particularly regarding hearing impairment. He expressed excitement about the results and anticipation for the REVEAL clinical trials for VRDN-003.
Future Plans
The Phase 3 clinical trial arm of THRIVE-2, evaluating veligrotug in patients with chronic TED, is ongoing, with topline data expected by the end of 2024. Viridian plans to submit a Biologics License Application for veligrotug for the treatment of TED in the second half of 2025.
Steve Mahoney, President and CEO of Viridian, highlighted the rapid onset of clinically meaningful responses and the favorable safety profile of veligrotug. He emphasized the potential for a more convenient treatment option with a shorter infusion regimen compared to the current standard of care.
