Viridian Therapeutics announced positive topline results from its Phase III THRIVE trial, demonstrating that veligrotug (VRDN-001) met all primary and secondary endpoints in patients with active thyroid eye disease (TED). The study's success marks a significant step forward in the treatment of this debilitating autoimmune condition, offering a potentially more effective and well-tolerated option for patients.
The THRIVE trial (NCT05176639) evaluated the efficacy and safety of veligrotug, an intravenously delivered anti-insulin-like growth factor-1 receptor (IGF-1R) antibody, in patients with active TED, also known as Graves’ disease. The results, announced on September 10, 2024, led to a 32% surge in Viridian Therapeutics' stock price.
Key Findings from the THRIVE Trial
After 15 weeks of treatment, patients receiving veligrotug showed highly statistically significant improvements across all measured signs and symptoms of TED. The trial's primary and secondary endpoints were met with notable efficacy and a favorable safety profile.
- Proptosis Response: The veligrotug treatment group achieved a 70% proptosis responder rate (PRR) compared to 5% in the placebo arm. Additionally, there was a 2.9mm mean reduction in proptosis from baseline in patients receiving veligrotug, compared with a 0.5mm reduction in patients receiving a placebo.
- Diplopia Resolution: 54% of patients treated with veligrotug experienced complete resolution of diplopia, compared to 12% of patients receiving a placebo. The diplopia response rate was 63% in the treatment group versus 20% in the placebo group.
- Overall Response Rate (ORR): Veligrotug demonstrated an ORR of 67% compared to 5% in the placebo group. ORR was defined as achieving a proptosis response and a reduction in clinical activity score (CAS).
- Rapid Onset of Action: More than half of the veligrotug-treated patients achieved a proptosis response after just one infusion, indicating a rapid onset of action.
- Safety Profile: Veligrotug was generally well-tolerated, with most adverse events (AEs) being mild. Notably, there were no treatment-related serious AEs reported.
Management Commentary
Steve Mahoney, President and CEO of Viridian Therapeutics, expressed his enthusiasm for the results, stating, “We were particularly pleased to observe the rapid onset of clinically meaningful responses across all endpoints, and veligrotug’s safety profile exceeded our expectations.”
Next Steps for Veligrotug
Viridian Therapeutics is currently conducting the THRIVE-2 study (NCT06021054) to evaluate veligrotug in patients with chronic TED, with topline data expected before the end of this year. The company plans to submit a biologics license application to the US Food and Drug Administration (FDA) in the second half of 2025.
Broader Pipeline Development
In addition to veligrotug, Viridian has initiated two Phase III trials, REVEAL-1 and REVEAL-2, for VRDN-003, a subcutaneous, half-life-extended anti-IGF-1R antibody with the same binding domain as veligrotug. This highlights Viridian's commitment to developing multiple options for treating TED.
Current Treatment Landscape
TED is an autoimmune condition characterized by inflammation and damage to tissues around the eyes. The current standard of care includes Amgen’s Tepezza (teprotumumab-trbw). The emergence of veligrotug as a potential treatment offers a new option with a promising profile.
