Viridian Therapeutics announces topline data from THRIVE trial of VRDN-001

Viridian Therapeutics announced topline data from the THRIVE phase 3 clinical trial of VRDN-001, now known as veligrotug, an intravenously delivered anti-insulin-like growth factor-1 receptor antibody, in patients with active thyroid eye disease, or TED. TED is an autoimmune condition characterized by inflammation, growth, and damage to tissues around and behind the eyes. THRIVE met the primary and all secondary endpoints at 15 weeks after five infusions of veligrotug, showing highly statistically significant improvements on all of the measured signs and symptoms of TED. Veligrotug additionally showed a rapid onset of action, with the majority of veligrotug-treated patients achieving a proptosis response after just 1 infusion, or 3 weeks after start of therapy. THRIVE enrolled 113 patients, randomized to veligrotug and placebo. Patients receiving veligrotug had statistically significant and clinically meaningful improvements across the following key disease endpoints at the primary efficacy analysis timepoint of 15 weeks: 70% proptosis responder rate, or PRR, in patients receiving veligrotug, compared with 5% of patients receiving placebo. PRR is defined as at least a 2-millimeter reduction in proptosis from baseline in the study eye without worsening in the fellow eye, as measured by exophthalmometry. 2.9 mm mean reduction in proptosis from baseline in patients receiving veligrotug, compared with 0.5mm reduction in patients receiving placebo, as measured by exophthalmometry. 54% complete resolution of diplopia in patients receiving veligrotug, compared with 12% of patients receiving placebo. Diplopia resolution is defined by patients achieving a score of 0 on the Gorman subjective diplopia scale at week 15, among patients with diplopia at baseline. 63% achieved a diplopia response in patients receiving veligrotug, compared with 20% of patients receiving placebo. Diplopia response is defined by patients achieving a reduction of at least 1 on the Gorman subjective diplopia scale at week 15, among patients with diplopia at baseline. 64% of patients receiving veligrotug achieved maximal or near-maximal therapeutic effect on CAS, compared with 18% of patients receiving placebo, defined as reaching a CAS of 0 or 1. CAS measures inflammatory signs and symptoms of TED, providing a composite score of pain, as well as redness and swelling of the eyelids and conjunctiva, on a scale from 0 to 7. 3.4-point mean reduction in CAS from baseline for patients receiving veligrotug, compared with 1.7-point reduction in patients receiving placebo. 67% of patients receiving veligrotug achieved an overall response, compared with 5% of patients receiving placebo. Overall Responder Rate is defined as achieving a proptosis response and a 2-point reduction in CAS from baseline without worsening in the fellow eye in either proptosis or CAS. Veligrotug was generally well-tolerated with a safety profile consistent with previous veligrotug studies. The majority of adverse events were mild, and there was a low rate of discontinuations in the veligrotug arm. There were no treatment-related serious AEs. There was a 5.5% placebo-adjusted rate of hearing impairment AEs in THRIVE. The second phase 3 clinical trial of veligrotug, THRIVE-2, in patients with chronic TED is ongoing. Viridian completed enrollment of THRIVE-2 in July, and topline data readout is on track for year-end 2024. Viridian anticipates submitting a BLA for veligrotug for the treatment of TED in 2H 2025, as planned. VRDN-003 is an IGF-1R antibody with the same binding domain as veligrotug and is believed to be the only anti-IGF-1R in development with an extended half-life. Viridian believes these topline results from THRIVE provide strong support for a potential best-in-class profile of VRDN-003, with the potential to deliver clinical efficacy and safety consistent with veligrotug in a low-volume, infrequent, self-administered, subcutaneous injection that patients take at home. Viridian initiated two global phase 3 clinical trials for VRDN-003 in August as planned: REVEAL-1 and REVEAL-2 in active and chronic TED, respectively. Both trials will evaluate VRDN-003 subcutaneously administered every Q4W or Q8W and will assess outcomes versus placebo. Viridian anticipates topline data from both trials in the first half of 2026, with a BLA submission for VRDN-003 for the treatment of TED by year-end 2026.