Viridian Therapeutics' veligrotug (VRDN-001) has demonstrated positive topline results in the THRIVE-2 Phase 3 clinical trial for patients with chronic thyroid eye disease (TED). The study, a randomized, double-masked, placebo-controlled trial, evaluated the efficacy and safety of veligrotug, an intravenously delivered anti-insulin-like growth factor-1 receptor (IGF-1R) antibody. The results, announced December 16, 2024, indicate that veligrotug met all primary and secondary endpoints, marking a significant step forward in the treatment of this debilitating autoimmune condition.
The THRIVE-2 trial enrolled 188 patients with chronic TED, randomizing 125 to veligrotug and 63 to placebo. Patients received five infusions of veligrotug, with efficacy assessments conducted at 15 weeks. The study's primary endpoints included proptosis responder rate (PRR), diplopia response, and changes in clinical activity score (CAS).
Key Efficacy Outcomes
Veligrotug demonstrated statistically significant improvements across all measured signs and symptoms of TED. Key findings include:
- Proptosis Responder Rate (PRR): 56% in veligrotug patients compared to 8% in placebo patients (p < 0.0001). The proptosis responder rate was statistically significant at all time points, including as early as 3 weeks after just one infusion.
- Diplopia Response: 56% of veligrotug patients achieved a diplopia response, compared with 25% of placebo patients (p = 0.0006). Rapid onset was observed as early as 6 weeks after just two infusions.
- Clinical Activity Score (CAS): 54% of veligrotug patients achieved maximal or near-maximal therapeutic effect on CAS, compared with 24% of placebo patients (p = 0.006).
According to Steve Mahoney, Viridian’s President and CEO, the THRIVE-2 results, combined with data from the THRIVE study, confirm veligrotug's potential to be the treatment-of-choice for all forms of active and chronic TED. Steven Leibowitz, M.D., Associate Clinical Professor of Ophthalmology, Stein Eye Institute, University of California Los Angeles and THRIVE-2 investigator, added that the results are highly encouraging, particularly the improvement in diplopia in chronic TED patients.
Safety and Tolerability
Veligrotug was generally well-tolerated, with a safety profile consistent with previous studies. The majority of adverse events were mild, and 94% of veligrotug-treated patients completed their treatment course. There was a 9.6% placebo-adjusted rate of hearing impairment adverse events.
BLA Submission and Future Plans
Viridian Therapeutics is on track to submit a Biologics License Application (BLA) for veligrotug in the second half of 2025. The company is also advancing VRDN-003, a subcutaneous anti-IGF-1R antibody, with topline data from the REVEAL-1 and REVEAL-2 Phase 3 clinical trials expected in the first half of 2026. VRDN-003 shares the same binding domain as veligrotug and is designed for convenient at-home self-administration.
With a strong cash position of $753 million as of September 30, 2024, Viridian is well-positioned to fund operations into the second half of 2027, including the commercial launch of veligrotug and the continued development of its pipeline.
