Viridian Therapeutics (Nasdaq: VRDN) reported that elegrobart (VRDN-003) met its primary endpoint in the Phase III REVEAL-2 trial in chronic thyroid eye disease (TED), with proptosis responder rates of 50% and 54% for the every-four-week and every-eight-week dosing arms, respectively, compared with 15% for placebo — results the company described as highly statistically significant at p < 0.0001 for both arms.
The REVEAL-2 trial is a randomized, placebo-controlled Phase III study that enrolled 204 patients with chronic thyroid eye disease, allocated 1:1:1 across elegrobart every four weeks (Q4W), elegrobart every eight weeks (Q8W), and placebo, with a primary analysis at week 24.
Elegrobart is a subcutaneously delivered, half-life-extended monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R). The proptosis responder rate served as the FDA primary endpoint, while an overall responder rate — defined as combined proptosis and Clinical Activity Score response — served as the EMA primary endpoint. Both were met with high statistical significance across both active arms. Mean proptosis reduction from baseline was -1.9 mm in the Q4W arm and -2.1 mm in the Q8W arm, versus -0.5 mm for placebo, again at p < 0.0001.
On diplopia, the Q4W arm achieved a 61% responder rate versus 38% for placebo (p = 0.0118), with complete diplopia resolution in 44% of Q4W patients versus 25% on placebo (p = 0.0295). The Q8W arm showed a 55% diplopia responder rate (p = 0.0419), though diplopia complete resolution in that arm did not reach statistical significance at p = 0.1304. Efficacy was reported as consistent regardless of baseline Clinical Activity Score. A total 91% of elegrobart-treated patients completed the full treatment course, and no treatment-related serious adverse events were observed. Rates of hearing impairment — a class effect associated with IGF-1R inhibition — were low, at placebo-adjusted rates of 4.1% and 8.8% in the Q4W and Q8W arms, respectively.
The chronic TED population is distinct from the active disease setting. Patients with chronic TED typically have lower inflammatory activity as measured by the Clinical Activity Score but can carry persistent proptosis and diplopia for years or decades. Treatment options in this population have historically been limited. The only approved IGF-1R inhibitor for TED is teprotumumab, an intravenous agent that established the mechanistic validity of IGF-1R blockade in this disease. Elegrobart's subcutaneous delivery and extended half-life are designed to enable less frequent dosing and home administration via autoinjector, which Viridian argues could expand uptake among patients who have not pursued intravenous infusion-based therapy. Cross-trial comparisons are limited by differences in patient populations, endpoints, and trial design, so direct efficacy comparisons between elegrobart and teprotumumab cannot be drawn from available data.
REVEAL-2 is the second positive pivotal Phase III readout for elegrobart, following REVEAL-1, which evaluated the drug in active TED. Viridian has also reported positive Phase III data for its intravenous IGF-1R antibody veligrotug from the THRIVE and THRIVE-2 trials in active and chronic TED, respectively. Veligrotug has received Breakthrough Therapy Designation from the FDA and is currently under Priority Review with a PDUFA target action date of June 30, 2026. The company intends to use the commercial and medical affairs infrastructure built for a potential veligrotug launch to support a subsequent elegrobart launch, if approved, with what it describes as limited incremental investment.