At the American Academy of Ophthalmology annual meeting, Viridian Therapeutics presented new top-line data from the phase 3 REVEAL-1 trial evaluating subcutaneous administration of elegrobart (VRDN-003), an investigational insulin-like growth factor-1 receptor antagonist, in patients with active thyroid eye disease (TED). The randomized, masked, placebo-controlled trial enrolled 132 adults with moderate-to-severe active TED, symptom onset within 15 months, proptosis ≥3 mm above normal, and a clinical activity score (CAS) ≥3. Patients were randomized 1:1:1 to receive elegrobart every 4 weeks (Q4W), every 8 weeks (Q8W), or placebo (44 patients per arm).
The trial met its primary endpoint at week 24, with a proptosis responder rate of 54% in the Q4W arm vs 18% with placebo (P<.0001). The Q8W arm achieved a 63% responder rate (P<.0001 vs placebo; nominal significance). Mean proptosis reductions were 2.33 mm and 2.50 mm with Q4W and Q8W dosing, respectively, compared with 0.81 mm with placebo (P <.0001 for both comparisons; nominal significance for Q8W).
Among patients with diplopia at baseline, 71% receiving Q4W elegrobart achieved a diplopia response vs 32% receiving placebo (P=.0009; nominal), while complete diplopia resolution occurred in 51% vs 16%, respectively (P =.0013; nominal). In the Q8W arm, diplopia response and resolution rates were 54% and 28%, respectively, but neither comparison met the nominal significance threshold.
By week 4, proptosis responder rates reached 30% and 31% in the Q4W and Q8W arms, respectively, compared with 8% with placebo. At week 24, 57% and 69% of patients receiving Q4W and Q8W elegrobart, respectively, achieved a CAS of 0 or 1, compared with 50% receiving placebo (P =.24 and P =.03, respectively); neither comparison met the prespecified significance threshold.
Most adverse events were mild. Muscle spasms occurred in 41% and 36% of patients receiving Q4W and Q8W elegrobart, respectively, vs 7% with placebo. Injection-site reactions occurred in 34%, 21%, and 16%, respectively. Hearing impairment events were reported in 14% of Q4W patients and 5% of Q8W patients, compared with 2% receiving placebo; all events in the elegrobart arms were tinnitus without reported hearing reduction. Four patients receiving elegrobart experienced serious adverse events, including 1 treatment-related event. One patient in the Q4W arm discontinued because of a treatment-emergent adverse event involving grade 1 amylase/lipase elevation, although no treatment-related adverse events led to discontinuation in either elegrobart arm.
Elegrobart demonstrated significant improvements in proptosis with both subcutaneous dosing schedules and clinically meaningful improvements in diplopia with Q4W treatment. With planned at-home autoinjector administration, elegrobart may offer a lower-burden treatment option.