Viridian Announces Positive Phase 3 Results for Chronic Thyroid Eye Disease Candidate

Veligrotug, an anti-insulin-like growth factor-1 receptor antibody, showed a promising reduction in proptosis.

Viridian Therapeutics (Massachusetts, USA) announced positive topline data from the Phase 3 THRIVE-2 clinical trial of veligrotug (veli) in patients with chronic thyroid eye disease (TED).

The company reported that veligrotug met all primary and secondary study endpoints in THRIVE-2, achieving a week 15 proptosis responder rate (PRR) of 56% (48% placebo-adjusted; p<0.0001). 

Veligrotug is an intravenously delivered anti-insulin-like growth factor-1 receptor (IGF-1R) antibody developed specifically for the chronic variant of this autoimmune disease. 

“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,” said Steve Mahoney, Viridian’s president and CEO. 

Viridian has indicated plans to submit a biologics licensing application (BLA) to the United States’ Food and Drug Administration (FDA) for veligrotug in the second half of 2025. 

Shares of the company’s stock (NASDAQ: VRDN) were up as high as 29% percent in Monday trading before settling to close at $21.54, compared to Friday’s close of $17.85.

Promise in proptosis

The data revealed that 56% of veligrotug patients achieved at least a 2mm reduction in proptosis without worsening in the fellow eye, compared to 8% in placebo (48% placebo-adjusted; p<0.0001). Response was rapid, observed as early as three weeks after one infusion.

The mean reduction in proptosis was 2.34mm in veligrotug-treated patients compared to 0.46mm in placebo-treated patients, resulting in a placebo-adjusted difference of 1.9mm (p<0.0001).

“We believe that these efficacy and safety results in only five 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 Mr. Mahoney.

Diplopia improvements

In the THRIVE-2 trial, 56% of veligrotug-treated patients showed at least a 1-point improvement on the Gorman diplopia scale, compared to 25% in the placebo group, resulting in a placebo-adjusted difference of 31% (p=0.0006). 

This improvement was observed as early as week 6 after two infusions. Additionally, 32% of veligrotug-treated patients achieved complete resolution of diplopia (score of 0), compared to 14% in the placebo group, with an 18% placebo-adjusted difference (p=0.0152).

Dr. Steven Leibowitz, Associate Clinical Professor of Ophthalmology at UCLA and THRIVE-2 investigator, highlighted the significance of the findings. “These data represent an incredible step forward for TED patients. I’ve been treating TED for over 30 years, and these results in the broadest population of TED patients are highly encouraging.”

“Resolving double vision or even improving it in chronic TED patients can really change their lives. I see veligrotug’s potential product profile as highly compelling with a rapid onset of treatment effect, diplopia benefit across a broad TED population, shorter dosing regimen, and favorable safety profile,” he added.

Reduction in inflammation (CAS)

The THRIVE-2 trial highlighted the impact of veligrotug on reducing inflammation in thyroid eye disease,  as measured by the Clinical Activity Score (CAS), a measure of inflammatory signs and symptoms in TED. 

A total of 54% of veligrotug-treated patients achieved near-complete resolution of inflammation, defined as a CAS of 0 or 1, compared to 24% of patients in the placebo group, reflecting a 29% placebo-adjusted difference (p=0.006). 

The mean reduction in CAS was 2.9 points in veligrotug-treated patients, compared to 1.3 points in the placebo group, yielding a placebo-adjusted difference of 1.6 points (p<0.0001). Furthermore, 56% of veligrotug-treated patients met the criteria for overall response, compared to just 7% in the placebo group, resulting in a 50% placebo-adjusted difference (p<0.0001).

56% of veligrotug-treated patients met criteria for overall response compared to 7% in placebo (50% placebo-adjusted; p<0.0001).

Safety profile

Veligrotug was generally well-tolerated, with most adverse events (AEs) reported as mild. Notably, 94% of veligrotug-treated patients completed the treatment course. The placebo-adjusted rate of hearing impairment was 9.6% (12.8% incidence in veligrotug-treated patients compared to 3.2% in placebo).

Study design and future developments

The study enrolled 188 patients, randomized to veligrotug (n=125) or placebo (n=63). The primary efficacy analysis was conducted at 15 weeks after five infusions. Results demonstrated statistically significant improvements across all measured endpoints, including proptosis, diplopia, and Clinical Activity Scores (CAS).

Viridian is also advancing its subcutaneous anti-IGF-1R antibody, VRDN-003, which shares veligrotug’s binding domain and is designed for at-home, low-volume, infrequent dosing. The company is conducting two Phase 3 trials, REVEAL-1 and REVEAL-2, for active and chronic TED. 

Topline data are expected in the first half of 2026.