Objective:

Evaluate subcutaneous elegrobart (VRDN-003), an investigational IGF-1 receptor antagonist, in adults with active thyroid eye disease (TED).

Approach:

• Study design: REVEAL-1 was a randomized, masked, placebo-controlled phase 3 trial of 132 adults with moderate-to-severe active TED.
• Treatment: Participants were assigned 1:1:1 to elegrobart every 4 weeks (Q4W), elegrobart every 8 weeks (Q8W), or placebo; each group included 44 patients.
• Assessment: The primary endpoint was proptosis response at week 24. The trial also assessed proptosis change, diplopia, clinical activity score (CAS), and adverse events.

Key Findings:

• At week 24, proptosis response was 54% with Q4W and 63% with Q8W elegrobart versus 18% with placebo (Q4W P<.0001; Q8W P<.0001, nominal).
• Mean proptosis reductions were 2.33 mm with Q4W and 2.50 mm with Q8W, compared with 0.81 mm with placebo (P<.0001 for both comparisons; Q8W nominal).
• Among patients with baseline diplopia, response rates were 71% with Q4W and 32% with placebo; complete resolution rates were 51% and 16%, respectively. Q8W rates were 54% and 28%; neither comparison met nominal significance.
• CAS of 0 or 1 at week 24 occurred in 57% with Q4W, 69% with Q8W, and 50% with placebo; neither elegrobart comparison met the prespecified significance threshold.
• Most adverse events were mild. Muscle spasms occurred in 41% with Q4W and 36% with Q8W versus 7% with placebo. Hearing impairment events were reported in 14%, 5%, and 2%, respectively; elegrobart-arm events were tinnitus without reported hearing reduction.

Interpretation:

The trial met its primary endpoint, with both elegrobart dosing schedules improving proptosis versus placebo. The source reports clinically meaningful diplopia improvements with Q4W treatment.

Limitations:

• The context provides top-line results and does not include further details on study methods or follow-up beyond week 24.
• Some reported comparisons were nominally significant; CAS comparisons did not meet the prespecified significance threshold.

Conclusion:

Four patients receiving elegrobart experienced serious adverse events, including one treatment-related event. One Q4W patient discontinued after a treatment-emergent grade 1 amylase/lipase elevation; no treatment-related adverse events led to discontinuation in either elegrobart arm.

Sources:

• Article context supplied by user