Phase 3 topline REVEAL-1 results for elegrobart for TED

Viridian Therapeutics issued a press release that announced the positive elegrobart topline results from the phase 3 REVEAL-1 clinical trial in which the drug was evaluated to treat active thyroid eye disease (TED).

The trial tested the effects of 2 regimens of subcutaneous elegrobart to treat TED eye disease, every-4-week and every-8-week (Q4W, Q8W, respectively) dosing compared with placebo.

The company described elegrobart as a “half-life-extended monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R).”

The study’s key takeaways, according to the press release, were:

• “REVEAL-1 met the primary endpoint of Q4W proptosis responder rate (PRR) with a highly statistically significant treatment effect.
• Elegrobart Q4W and Q8W achieved clinically meaningful 54% and 63% PRR versus 18% placebo at week 24.
• Complete resolution of diplopia in 51% of patients treated Q4W versus 16% placebo at week 24.
• Elegrobart was generally well tolerated in both dose groups with low rates of hearing impairment.

Vivirdian noted that the topline readout from REVEAL-2, a phase 3 trial evaluating the effect of elegrobart on chronic TED, is on track for the second quarter of 2026. Submission of the Biologics License Application is expected in the first quarter of 2027.

Steve Mahoney, Viridian Therapeutics’s President and Chief Executive Officer commented, “We are excited to report these results from REVEAL-1, the largest pivotal clinical trial conducted in active TED to date, which position elegrobart as potentially the first-ever subcutaneous autoinjector treatment for TED. REVEAL-1 met its primary endpoint with high statistical significance. Elegrobart treatment drove robust proptosis responses in a treatment regimen comprised of as few as three subcutaneous doses. Further, in the Q4W arm, we saw clinically meaningful diplopia responses and diplopia resolution.”

This finding with few subcutaneous doses is in contrast to a commercially available treatment for TED, ie, Tepezza (teprotumumab-trbw, Horizon Therapeutics) that requires eight intravenous infusions.

Elegrobart REVEAL-1 study

A total of 132 patients were enrolled in REVEAL-1 to assess the efficacy and safety of subcutaneous Q4W or Q8W. They were randomized 1:1:1 to elegrobart Q4W (n=44), elegrobart Q8W (n=44), and placebo (n=44).

REVEAL-1 showed highly statistically significant primary endpoints of the two doses tested for the PRR (P < 0.0001 for both comparisons with placebo).

Both dosing regimens also showed highly statistically significant results in the mean proptosis change from baseline (P < 0.0001 for both comparisons with placebo).

Regarding safety, the company also reported the elegrobart was “generally well-tolerated with a safety profile consisting of adverse events generally expected from the anti-IGF-1R class, the vast majority of which were mild.”

The rates of hearing impairment associated with elegrobart were low in the Q4W and Q8W dosing regimens, ie, 11.3% and 2.3% placebo-adjusted rates, respectively. All hearing impairment was reported to be cases of tinnitus and were not associated with reductions in hearing, according to the press release.

The company is also evaluating veligrotug, an investigational intravenously injected drug to treat TED. with the potential to be the IV treatment-of-choice for active and chronic TED patient. The company announced that veligrotug is on track with a Prescription Drug User Fee Act date of June 30, 2026.