Viridian Therapeutics (VRDN) Study result summary

Study background and design

• REVEAL-2 is a phase III pivotal trial evaluating elegrobart (Ellay) in chronic Thyroid Eye Disease (TED), enrolling 204 patients, the largest TED trial to date.

• Patients were randomized to Q4 weekly, Q8 weekly, or placebo arms, with broad inclusion criteria for clinical activity score (CAS).

• The primary endpoint was proptosis responder rate at week 24 in the Q4 arm; key secondary endpoints included proptosis in Q8, mean change from baseline, and diplopia outcomes.

• Both Q4 and Q8 regimens involved as few as three doses, delivered via subcutaneous auto-injector.

• Baseline characteristics were balanced, with most patients female and average age just over 50.

Efficacy results

• REVEAL-2 met its primary endpoint: Q4 weekly elegrobart achieved a 50% proptosis responder rate vs. 15% for placebo, highly statistically significant.

• Q8 weekly arm also showed a 54% proptosis responder rate, with significant mean reductions in proptosis for both dosing arms.

• Diplopia response was 61% in Q4 arm vs. 38% for placebo, with 44% achieving complete resolution.

• Both Q4 and Q8 arms showed rapid onset of effect, with separation from placebo after week 4, deepening through week 24.

• Efficacy was consistent across subgroups, including low and high CAS at baseline.

Safety and tolerability

• Elegrobart was generally well-tolerated, with most adverse events (AEs) mild and consistent with the IGF-1R class.

• Hearing impairment rates were low (4.1% Q4, 8.8% Q8, placebo-adjusted), mostly tinnitus; mild hypoacusis and eustachian tube disorder were rare and resolved.

• Injection site reactions were mostly grade 1 and more frequent in placebo than treatment arms; none led to discontinuation.

• Discontinuations were rare (3 cases), due to manageable AEs such as hyperglycemia, tinnitus, and muscle spasm.

• 91% of elegrobart-treated patients completed the full course; no treatment-related serious adverse events occurred.