Viridian announces topline data from THRIVE-2 phase 3 clinical trial of veligrotug for treatment of thyroid eye disease

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Viridian Therapeutics has announced topline data from THRIVE-2, (NCT06021054) its phase 3 clinical trial of VRDN-001 (veligrotug), an intravenously delivered anti-insulin-like growth factor-1 receptor (IGF-1R) antibody, in patients with chronic thyroid eye disease (TED).

THRIVE-2 is a randomized, double-masked, placebo-controlled safety, tolerability and efficacy study of VRDN-001 in participants with chronic TED. It compares a 5-dose treatment arm of VRDN-001 to placebo, each dosed 3 weeks apart. It enrolled 188 patients, with 125 randomized to veligrotug and 63 to placebo.^1,2

Steve Mahoney, Viridian’s President and CEO commented on the results in a press release from the company.¹

“We are extremely pleased to announce better-than-expected THRIVE-2 results generated in the broadest population of chronic TED patients studied in a global phase 3 study to date. We believe that these efficacy and safety results in only 5 infusions, combined with our compelling data from THRIVE, confirm the potential of veli to be the treatment-of-choice for all forms of active and chronic TED,” said Mahoney.

According to the company, THRIVE-2 met all primary and secondary endpoints at the 15-week primary analysis timepoint after 5 infusions of veligrotug. Furthermore, the drug showed “statistically significant responses on all of the measured signs and symptoms of TED” including proptosis, clinical activity score (CAS), and diplopia.¹

The Proptosis Responder Rate (PRR) in patients treated with veligrotug was 56%, compared to 8% in placebo patients. According to the company¹, PRR was statistically significant at all time points, including as early as 3 weeks after just 1 infusion. While the mean reduction of proptosis was 2.34mm from baseline in patients treated with veligrotug, compared to 0.46mm reduction in placebo patients.

Further data showed that 56% of patients treated with veligrotug also saw a diplopia response, compared with 25% of placebo patients, while 32% of veligrotug patients achieved complete resolution of diplopia, compared with 14% of placebo patients.

CAS was also measured in patients in the trial. 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. Results showed 54% of veligrotug patients achieved “maximal or near-maximal therapeutic effect” on CAS, compared with 24% of placebo patients. This is defined as reaching a CAS of 0 or 1, among patients with a CAS of ≥ 3 at baseline. Those treated with veligrotug also saw a mean reduction of CAS of 2.9 from baseline compared to 1.3 In placebo patients.

According to the company¹, veligrotug was “generally well tolerated” and had a safety profile consistent with previous veligrotug studies including THRIVE. Viridian also reported a low rate of hearing impairment as a result of treatment, with 12.8% incidence in veligrotug patients, compared with 3.2% incidence in placebo patients.

Looking forward, the company is currently dosing patients in two global phase 3 clinical trials for VRDN-003, REVEAL-1 and REVEAL-2, in active and chronic TED, respectively. The company expects topline data from the trials in the first half of 2026 and plans to submit a BLA for VRDN-003 by the end of 2026.

References:

1. Viridian Therapeutics Announces Positive Topline Results from Veligrotug Phase 3 THRIVE-2 Clinical Trial in Patients with Chronic Thyroid Eye Disease. Press Release; December 16, 2024. Accessed December 18, 2024. https://investors.viridiantherapeutics.com/news/news-details/2024/Viridian-Therapeutics-Announces-Positive-Topline-Results-from-Veligrotug-Phase-3-THRIVE-2-Clinical-Trial-in-Patients-with-Chronic-Thyroid-Eye-Disease/default.aspx

2. A Safety, Tolerability and Efficacy Study of VRDN 001 in Healthy Volunteers and Persons With Thyroid Eye Disease (TED) (THRIVE). NCT05176639. https://www.clinicaltrials.gov/study/NCT05176639?spons=Viridian%20Therapeutics,%20Inc.&rank=2&page=1&limit=10