Viridian Announces Topline Results from Veligrotug Phase 3 Trial in Patients with Chronic TED

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

“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 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,” Steve Mahoney, Viridian’s President and CEO, said in a company news release. “The robustness and consistency of our data, similar to THRIVE, showed strong and rapid responses in categories that we believe matter most to patients including proptosis reduction, diplopia resolution and improvements in Clinical Activity Scores. This is the first product candidate to demonstrate a diplopia response and resolution rate in a global chronic TED phase 3 study."

Mr. Mahoney said the company's BLA preparation work is underway.

"The combined results of THRIVE and THRIVE-2, give us even higher conviction that our subcutaneous VRDN-003 program will deliver positive topline data in the first half of 2026, which would enable a BLA submission in the second half of 2026," he said. 

THRIVE-2 Phase 3 Topline Results

THRIVE-2 met all primary and secondary endpoints at the 15-week primary analysis timepoint after five infusions of veligrotug, showing statistically significant responses on all of the measured signs and symptoms of TED: proptosis, CAS, and diplopia. THRIVE-2 enrolled a total of 188 patients, randomized to veligrotug (n=125) and placebo (n=63). The mean time since onset of TED in this patient population was 69.8 months.

The key data at the primary efficacy analysis timepoint of 15 weeks are as follows:

Proptosis:

• Proptosis Responder Rate (PRR): 56% in veligrotug patients, compared with 8% in placebo patients (48% placebo-adjusted, P<0.0001). PRR was statistically significant at all time points, including as early as 3 weeks after just one infusion, demonstrating a rapid onset of response. PRR is defined as at least a 2-millimeter (mm) reduction in proptosis from baseline in the study eye without worsening in the fellow eye (≥ 2 mm increase), as measured by exophthalmometry. PRR results as measured by MRI/CT were consistent with those measured by exophthalmometry at the primary efficacy analysis timepoint.
• Proptosis Mean Reduction: 2.34mm mean reduction in proptosis from baseline in veligrotug patients, compared with 0.46mm reduction in placebo patients (1.9mm placebo-adjusted, P<0.0001).

Diplopia:

• Diplopia Response: 56% of veligrotug patients achieved a diplopia response, compared with 25% of placebo patients (31% placebo-adjusted, P=0.0006). Rapid onset was observed as early as 6 weeks after just two infusions. Diplopia response is defined as patients achieving a reduction of at least 1 on the Gorman subjective diplopia scale at week 15, for those patients with diplopia at baseline (n=102).
• Diplopia Complete Resolution: 32% of veligrotug patients achieved complete resolution of diplopia, compared with 14% of placebo patients (18% placebo-adjusted, P=0.0152). Rapid onset was observed as early as 6 weeks after just two infusions. Diplopia resolution is defined as patients achieving a score of 0 on the Gorman subjective diplopia scale at week 15, for those patients with diplopia at baseline.

Clinical Activity Score (CAS):

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.

• CAS Reduction to 0 or 1: 54% of veligrotug patients achieved maximal or near-maximal therapeutic effect on CAS, compared with 24% of placebo patients (29% placebo-adjusted, p=0.006), defined as reaching a CAS of 0 or 1, among patients with a CAS of ≥ 3 at baseline (n=104).
• CAS Mean Reduction: 2.9-point mean reduction in CAS from baseline in veligrotug patients, compared with 1.3-point reduction in placebo patients (1.6-point placebo-adjusted, P<0.0001), among patients with a CAS of ≥ 3 at baseline.

Overall Response:

• Overall Responder Rate: 56% of veligrotug patients achieved an overall response, compared with 7% of placebo patients (50% placebo-adjusted, P<0.0001). Overall Responder Rate is defined as achieving a proptosis response without worsening of CAS from baseline (≥ 1 point increase) and without worsening in the fellow eye in either proptosis (2 mm increase) or CAS.

THRIVE-2 Safety Data

• Generally Well-Tolerated: Veligrotug was generally well-tolerated with a safety profile consistent with previous veligrotug studies including THRIVE. The majority of adverse events (AEs) were mild, and 94% of veligrotug-treated patients completed their treatment course.
• Low Rate of Hearing Impairment: There was a 9.6% placebo-adjusted rate of hearing impairment AEs (12.8% incidence in veligrotug patients, compared with 3.2% incidence in placebo patients).

“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,” said Steven Leibowitz, M.D., Associate Clinical Professor of Ophthalmology, Stein Eye Institute, University of California Los Angeles and THRIVE-2 investigator. “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.”

Viridian also announced that subcutaneous VRDN-003, 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, is on track to report topline data in the first half of 2026. Viridian 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.