Elegrobart Meets Phase 3 Primary Endpoint in TED

Clinical Scorecard: REVEAL-1 Meets Phase 3 Primary Endpoint for Elegrobart in TED

At a Glance

Category	Detail
Condition	Active thyroid eye disease (TED)
Key Mechanisms	Elegrobart (VRDN-003) is an investigational insulin-like growth factor-1 receptor antagonist administered subcutaneously.
Target Population	Adults with moderate-to-severe active TED, symptom onset within 15 months, proptosis at least 3 mm above normal, and clinical activity score (CAS) of at least 3.
Care Setting	Phase 3 clinical trial evaluating subcutaneous treatment in adults with active TED.

Key Highlights

In the randomized, masked, placebo-controlled REVEAL-1 trial, 132 adults were assigned to elegrobart every 4 weeks (Q4W), every 8 weeks (Q8W), or placebo.
At week 24, proptosis responder rates were 54% with Q4W and 63% with Q8W, versus 18% with placebo; the primary endpoint was met.
Mean proptosis reductions at week 24 were 2.33 mm with Q4W and 2.50 mm with Q8W, compared with 0.81 mm with placebo.
Among patients with baseline diplopia, response and complete resolution rates were 71% and 51% with Q4W, versus 32% and 16% with placebo; Q8W comparisons did not meet nominal significance.
Most adverse events were mild; muscle spasms, injection-site reactions, and hearing impairment events were reported.

Guideline-Based Recommendations

Diagnosis

Trial eligibility required moderate-to-severe active TED, symptom onset within 15 months, proptosis at least 3 mm above normal, and CAS of at least 3.

Management

The trial evaluated subcutaneous elegrobart every 4 weeks or every 8 weeks against placebo; the article does not provide clinical treatment recommendations.

Monitoring & Follow-up

The article reports assessment of proptosis, diplopia, CAS, and adverse events through week 24.

Risks

Muscle spasms occurred in 41% with Q4W and 36% with Q8W, versus 7% with placebo.
Injection-site reactions occurred in 34% with Q4W, 21% with Q8W, and 16% with placebo.
Hearing impairment events were reported in 14% with Q4W, 5% with Q8W, and 2% with placebo; elegrobart-arm events were tinnitus without reported hearing reduction.
Four elegrobart-treated patients experienced serious adverse events, including one treatment-related event. One Q4W patient discontinued after a treatment-emergent grade 1 amylase/lipase elevation.

Patient & Prescribing Data

The trial enrolled 132 adults with moderate-to-severe active TED meeting the stated symptom-duration, proptosis, and CAS criteria; 44 patients were assigned to each arm.

Elegrobart was administered subcutaneously every 4 or 8 weeks. The article describes planned at-home autoinjector administration but provides no prescribing instructions.

Clinical Best Practices

The article reports nominal significance for several comparisons; neither CAS comparison met the prespecified significance threshold.