Development

Viridian Therapeutics' elegrobart meets primary endpoint in Phase III active thyroid eye disease trial

Viridian Therapeutics (Nasdaq: VRDN) reported Phase III data from the REVEAL-1 trial showing that elegrobart, a subcutaneous anti-IGF-1R monoclonal antibody, met its primary endpoint in active thyroid eye disease with a proptosis responder rate of 54% (Q4W) versus 18% for placebo at week 24 — positioning the drug as a potential first self-administered autoinjector in a market currently served only by intravenous therapy.

REVEAL-1 is a randomized, placebo-controlled Phase III trial enrolling 132 patients with active thyroid eye disease, randomized 1:1:1 across elegrobart Q4W, elegrobart Q8W, and placebo arms (n=44 each).

The Q4W arm met the FDA-defined primary endpoint of proptosis responder rate at 54% versus 18% placebo (p<0.0001). The Q8W arm, assessed as a secondary endpoint, produced a 63% responder rate against the same placebo comparator. Mean proptosis reduction from baseline by exophthalmometry was -2.33 mm (Q4W) and -2.50 mm (Q8W), compared with -0.81 mm for placebo. In the Q4W arm, 51% of patients achieved complete diplopia resolution versus 16% on placebo; this was one of several secondary measures reported by the company, but falls below the prespecified hierarchy break. The clinical activity score endpoint — reduction to 0 or 1 — was not statistically significant in the Q4W arm (57% vs 50%, p=0.24). The Q8W arm posted a nominally significant result on this measure (69% vs 50%, p=0.03), though interpretation is limited by the study’s testing hierarchy.

Adverse events were predominantly mild and consistent with the anti-IGF-1R class. Placebo-adjusted hearing impairment rates were 11.3% in the Q4W arm and 2.3% in the Q8W arm; all events were tinnitus, with no audiometric hearing loss reported.

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Elegrobart is a half-life-extended monoclonal antibody targeting IGF-1R, the same receptor blocked by teprotumumab (Tepezza), the only currently approved pharmacotherapy for TED. Viridian said the only marketed TED therapy, Tepezza, annualized to roughly USD 2 billion in 2025 revenue despite what it described as low market penetration. Amgen separately reported Tepezza sales increased 3% for full-year 2025. Tepezza requires eight intravenous infusions administered at an infusion center over around five months. Elegrobart's subcutaneous autoinjector format, requiring as few as three doses in the Q8W regimen, is the primary differentiating feature. Whether the convenience advantage translates into materially superior real-world uptake will depend on pricing, payer access, and physician adoption patterns that cannot be assessed from trial data alone. Cross-trial comparisons with teprotumumab's pivotal efficacy data are limited by differences in trial design and patient selection.

Viridian's second elegrobart pivotal trial, REVEAL-2, evaluating the drug in chronic TED, is on track for a topline readout in Q2 2026, with a BLA submission to the US FDA anticipated in Q1 2027.


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