Viridian Therapeutics (NASDAQ:VRDN) reported top-line results from its REVEAL-1 Phase III clinical trial evaluating subcutaneous (SC) elegrobart (ELE) in patients with active thyroid eye disease (TED), saying the study met its primary endpoint and showed “clinically meaningful activity across multiple key endpoints,” according to President and CEO Steve Mahoney.
Primary endpoint met; proptosis and diplopia outcomes highlighted
Mahoney said REVEAL-1 met its primary endpoint in the Q4 weekly dosing arm, with a “highly statistically significant treatment effect” on proptosis responder rate at week 24 as measured by exophthalmometry. He cited proptosis responder rates of 54% in the Q4 weekly arm and 63% in the Q8 weekly arm, compared with 18% in the placebo arm.
Chief Medical Officer Radhika Tripuraneni provided additional details on trial design and endpoints. REVEAL-1 enrolled 132 patients with active TED, randomized 1:1:1 into two active treatment arms (Q4 weekly and Q8 weekly) and placebo. In each treatment arm, patients received a loading dose of two injections (600 mg), followed by five single-injection doses in the Q4 arm; patients in the Q8 arm received two single-injection doses.
Tripuraneni said REVEAL-1 met both the U.S. and European primary endpoints, noting that FDA and EMA requested different primary endpoints. She reported that Q4 weekly ELE showed a 54% proptosis responder rate by exophthalmometry versus 18% for placebo, and a 51% overall responder rate versus 16% for placebo.
Secondary endpoints and statistical hierarchy
Tripuraneni said fixed hierarchical testing was used for key secondary endpoints, with Q4 weekly endpoints tested before Q8 weekly endpoints. She said the clinical activity score (CAS) reduction to 0 or 1 in the Q4 weekly arm did not achieve statistical significance due to an “unexpected and large placebo response.” Because CAS 0/1 appeared early in the hierarchy, subsequent pre-specified endpoints are considered “nominally significant,” she said, despite low p-values.
On diplopia, Tripuraneni said 51% of patients in the Q4 weekly arm achieved complete resolution versus 16% on placebo, and 71% achieved a diplopia response versus 32% on placebo. For Q8 weekly dosing, she cited a 63% proptosis responder rate and a 2.5 mm mean reduction in proptosis from baseline, highlighting that the Q8 regimen required “only three doses.”
Viridian also reported MRI-based assessments of proptosis, reviewed by two independent masked central readers. Tripuraneni said MRI measures “confirmed a clinically meaningful benefit” and provided independent confirmation consistent with exophthalmometry.
Rapid onset and safety observations
Management described early onset of effect. Tripuraneni said 30% of patients achieved a proptosis response at week four after a single dose, with separation from placebo sustained through week 24. She also said diplopia response and complete resolution showed separation as early as week four with Q4 weekly dosing.
On safety, Tripuraneni said ELE was “generally well-tolerated” and that most adverse events were mild. She reported two discontinuations due to adverse events—one in the Q4 arm and one in placebo. Hearing-related events were described as low and limited to tinnitus in both active arms, with “no associated reductions in hearing.” Tripuraneni added that the only hypoacusis event occurred in the placebo arm.
Injection site reactions were mostly grade 1, with one grade 2 erythema, and none led to interrupted dosing or discontinuation, she said. Tripuraneni also noted REVEAL-1 dosing was performed using vial and syringe at the clinical site, and that the company is completing an auto-injector bridging study with plans to launch with a low-volume auto-injector.
Regulatory plans: BLA timing and dual-regimen strategy
Viridian said it expects to submit a biologics license application (BLA) for ELE in the first quarter of 2027 and plans to seek approval for both Q4 and Q8 regimens. Tripuraneni said the company is also looking ahead to REVEAL-2, a Phase III trial in chronic TED that is “on track for top-line data in the second quarter of 2026” and will enroll over 200 patients, according to Chief Business Officer Shan Wu.
On a question about whether the statistical hierarchy could create approval risk for Q8 dosing or for inclusion of certain endpoints in labeling, Mahoney said the company is “very confident” it can move both regimens forward, emphasizing that the trial met its primary endpoint. Wu added that the primary endpoint and the EU primary endpoint were both highly statistically significant and said the data “unequivocally supports a positive study.” Wu said the company intends to seek inclusion of additional endpoints in labeling and cited “many precedents” for doing so.
Commercial positioning: convenience and market expansion
Mahoney and Chief Commercial Officer Tony Casciano framed ELE as potentially the first SC auto-injector for at-home self-administration in TED, with dosing as few as three doses. Mahoney said the TED market is “annualizing at approximately $2 billion today,” despite being served by a single IV therapy, and argued there is a need to make treatment easier.
Casciano said the company believes market penetration for the existing IV therapy is in the “single digit” range and that expanding access is a key growth lever. He also cited company research indicating “roughly 30% of patients that are offered” the existing IV therapy refuse it due to treatment burden, describing the infusion schedule as logistically challenging.
Management also discussed Viridian’s broader TED portfolio. Mahoney highlighted that the company’s next-generation IV program, veligrotug, is under FDA priority review with a PDUFA target action date of June 30, and said Viridian has built a commercial and medical affairs organization in preparation for a potential launch.
About Viridian Therapeutics (NASDAQ:VRDN)
Viridian Therapeutics, Inc (NASDAQ: VRDN) is a clinical-stage biopharmaceutical company focused on the discovery and development of targeted antibody therapeutics for patients suffering from rare and serious diseases. The company’s lead program, VRDN-001, is a fully human monoclonal antibody that antagonizes the insulin-like growth factor-1 receptor (IGF-1R), with an initial focus on thyroid eye disease (TED). By selectively inhibiting IGF-1R signaling, VRDN-001 aims to reduce inflammation and tissue remodeling associated with TED and related disorders.
In addition to VRDN-001, Viridian is advancing a second antibody program, VRDN-002, which targets complement-mediated pathways implicated in autoimmune and inflammatory diseases.
