Viridian Therapeutics REVEAL-2 Hits Phase 3 Endpoint, Shows “IV-like” Proptosis Gains in Chronic TED

Key Points

• REVEAL-2 met its primary endpoint in chronic TED: the Q4-weekly arm had a 50% proptosis responder rate versus 15% for placebo (Q8-weekly 54% vs placebo) with mean proptosis reductions of ~1.9–2.1 mm versus 0.52 mm and separation from placebo seen after a single dose.
• Diplopia improvement is a key differentiator: the Q4 arm achieved a 61% diplopia response versus 38% on placebo and 44% complete resolution at Week 24, making Ellay the first subcutaneous therapy to demonstrate impact on diplopia in chronic TED.
• Regulatory and commercial plans underway: Viridian aims to file a BLA in Q1 2027 and is developing a one‑step auto‑injector for at‑home dosing (Q8 likely the preferred regimen), while IV veligrotug holds Breakthrough designation and has a PDUFA target date of June 30.

Viridian Therapeutics NASDAQ: VRDN reported positive top-line results from REVEAL-2, a Phase 3 pivotal trial evaluating subcutaneous elegrobart (Ellay) in patients with chronic thyroid eye disease (TED), saying the study met its primary endpoint with “IV-like” improvements in proptosis and showed meaningful benefits on double vision (diplopia) in one dosing arm.

REVEAL-2 met primary endpoint in chronic TED

Chief Medical Officer Radhika Tripuraneni said REVEAL-2 met the trial’s primary endpoint of proptosis responder rate in the Q4-weekly arm at Week 24, with a 50% responder rate versus 15% on placebo, which she described as “highly statistically significant.” Tripuraneni added that the Q8-weekly arm also produced a “highly statistically significant” proptosis responder rate of 54% versus placebo.

Tripuraneni also highlighted statistically significant improvements in mean proptosis change from baseline, reporting reductions of 1.88 mm and 2.08 mm in the Q4 and Q8 arms, respectively, compared with a 0.52 mm reduction in the placebo arm. She said separation from placebo was observed after Week 4 and deepened through Week 24, with mean proptosis changes separating from placebo at Week 4 “after just a single dose” in both treatment arms.

Diplopia data highlighted in Q4 arm

Viridian emphasized diplopia outcomes as a key differentiator in chronic TED. Tripuraneni said 61% of patients in the Q4-weekly arm achieved a diplopia response versus 38% on placebo, and 44% achieved complete resolution of diplopia at Week 24. She characterized REVEAL-2 as “the first and only subcutaneous therapy to have demonstrated impact on diplopia for the chronic TED population.”

Tripuraneni noted that REVEAL-2 also met the European Union primary endpoint of overall responder rate “with high statistical significance,” adding that U.S. and EU regulators requested different primary endpoints.

Study design and patient population

REVEAL-2 enrolled patients with chronic TED and included patients with any clinical activity score (CAS) at baseline, which Tripuraneni said was intended to capture the “broadest possible” chronic population. Patients were randomized to Q4-weekly Ellay, Q8-weekly Ellay, or placebo. She said the study enrolled 204 patients and described it as “the largest pivotal clinical trial ever run in TED,” adding that 91% of treated patients completed therapy.

Tripuraneni said baseline characteristics were generally well-balanced across arms, with most participants female and an average age just over 50.

During the Q&A, Chief Business Officer Shan Wu said the company was “really excited” by the consistency of proptosis and diplopia results regardless of baseline CAS. He said results in the low-CAS subgroup were generally consistent with the overall trial and suggested the higher-CAS subgroup was also generally consistent with overall REVEAL-2 outcomes.

Safety profile and discontinuations

Tripuraneni said Ellay was generally well-tolerated, with most adverse events mild and a safety profile consistent with the IGF-1R class and with the company’s REVEAL-1 trial in active TED. She reported low rates of hearing impairment, citing placebo-adjusted rates of 4.1% in the Q4 arm and 8.8% in the Q8 arm. For those reporting hearing impairment, she said “the majority reported tinnitus.”

Tripuraneni added that two participants in each treatment arm reported mild hypoacusis (reduced hearing), completed treatment with no dosing interruptions, and had “no detectable changes in hearing at the end of their treatment period.” She also noted mild cases of eustachian tube disorder in both active arms.

Asked about discontinuations, Tripuraneni said adverse events leading to discontinuation included grade 2 hyperglycemia in Q4, grade 1 tinnitus in Q8, and a grade 3 muscle spasm described as a “foot cramp” in Q8. She said the events were generally noted “somewhere in the middle” of therapy.

Regulatory timeline, dosing strategy, and commercial positioning

President and CEO Steve Mahoney said Viridian plans to submit a biologics license application (BLA) for Ellay in Q1 2027. Mahoney positioned Ellay as a potential first subcutaneous auto-injector option for both active and chronic TED, with the potential for “as few as three doses” and at-home self-administration using a one-step auto-injector.

Chief Commercial Officer Tony Casciano said Viridian intends to seek approval for both Q4-weekly and Q8-weekly dosing regimens, and said the company views Q8 as the likely “go-to” regimen for most patients, with potential use of Q4 for patients with heavier diplopia burden based on feedback from key opinion leaders.

Mahoney also contrasted Viridian’s planned auto-injector approach with an on-body infusion device under development for TEPEZZA, describing that competitor approach as a wearable infusion delivered every two weeks for 12 infusions over 24 weeks. Mahoney said Viridian plans to use “a commercially validated” auto-injector that delivers a dose “in seconds,” adding that the company uses “the same auto-injector pen as is used with Dupixent.”

Separately, Viridian discussed its nearer-term TED product opportunity with IV veligrotug. Mahoney noted veligrotug has been granted Breakthrough Therapy designation and Priority Review and is “on track” for a PDUFA target date of June 30. Casciano said Viridian has built a commercial and medical affairs organization and is “fully staffed and fully prepared” for launch.

On market dynamics, Casciano described the TED market as roughly $2 billion today with one approved competitor, and said Viridian’s market research suggests up to 30% of patients offered TEPEZZA decline therapy, often citing administration burden. He said Viridian believes the market “can at least double at maturity,” citing potential drivers including improved patient acceptance, activating more prescribers (including endocrinology and general ophthalmology), expanded treatment of milder patients, and increased promotional effort.

On chronic penetration, Casciano said TEPEZZA use in chronic TED is low, noting that of about 7,000 patients annually initiated on TEPEZZA, roughly 80% are active patients, leaving chronic penetration “extremely low.” He added that chronic patients are often seen long-term by endocrinologists for Graves’ disease, which he said provides a pathway to reach chronic patients, particularly with an at-home subcutaneous option.

Viridian also said it is developing an auto-injector in parallel with its pivotal studies. Wu said the pivotal REVEAL studies used vial-and-syringe dosing, while a parallel auto-injector study has completed enrollment and is intended to support submission “in time for BLA” with the goal of launching in an auto-injector.

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.

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