Elegrobart Meets Phase 3 Primary Endpoint in TED

Clinical Report: Elegrobart Meets Phase 3 Primary Endpoint in TED

Overview

In the phase 3 REVEAL-1 trial, subcutaneous elegrobart met its primary endpoint at week 24: proptosis response occurred in 54% of patients receiving dosing every 4 weeks and 63% receiving dosing every 8 weeks, versus 18% with placebo. Q4W treatment also improved diplopia response and complete resolution versus placebo; most adverse events were reported as mild, with muscle spasms the most frequent event in the elegrobart groups.

Background

Thyroid eye disease (TED) is assessed by activity and severity, with the Clinical Activity Score (CAS) used to characterize disease activity. The REVEAL-1 trial evaluated elegrobart, an investigational insulin-like growth factor-1 receptor antagonist, in adults with moderate-to-severe active TED. Participants had symptom onset within 15 months, proptosis at least 3 mm above normal, and CAS of at least 3. The 2021 EUGOGO guideline recommends activity- and severity-based assessment and multidisciplinary care; for active, moderate-to-severe TED, it recommends intravenous methylprednisolone plus oral mycophenolate sodium as first-line therapy.

Data Highlights

Outcome	Q4W elegrobart	Q8W elegrobart	Placebo
Patients randomized	44	44	44
Proptosis response at week 24	54%	63%	18%
Mean proptosis reduction at week 24	2.33 mm	2.50 mm	0.81 mm
Diplopia response among patients with baseline diplopia	71%	54%	32%
Complete diplopia resolution among patients with baseline diplopia	51%	28%	16%
CAS of 0 or 1 at week 24	57%	69%	50%
Muscle spasms	41%	36%	7%
Injection-site reactions	34%	21%	16%
Hearing impairment events	14% (tinnitus without reported hearing reduction)	5% (tinnitus without reported hearing reduction)	2%

Key Findings

REVEAL-1 was a randomized, masked, placebo-controlled phase 3 trial of 132 adults, assigned equally to Q4W elegrobart, Q8W elegrobart, or placebo.
At week 24, proptosis response was 54% with Q4W and 63% with Q8W, compared with 18% with placebo; the reported P value was less than .0001 for both comparisons, with Q8W significance described as nominal.
Mean proptosis reduction was 2.33 mm with Q4W and 2.50 mm with Q8W, versus 0.81 mm with placebo; both comparisons were reported at P less than .0001, with Q8W significance described as nominal.
Among patients with baseline diplopia, response rates were 71% with Q4W and 32% with placebo (P=.0009; nominal), while complete resolution rates were 51% and 16%, respectively (P=.0013; nominal). Q8W diplopia response and resolution rates were 54% and 28%; neither comparison met the nominal significance threshold.
By week 4, proptosis response rates were 30% with Q4W and 31% with Q8W, compared with 8% with placebo.
At week 24, CAS of 0 or 1 was reported in 57% with Q4W, 69% with Q8W, and 50% with placebo; neither elegrobart comparison met the prespecified significance threshold. Most adverse events were mild; four elegrobart-treated patients had serious adverse events, including one treatment-related event.

Clinical Implications

The trial reports proptosis improvements with both subcutaneous dosing schedules and diplopia improvements with Q4W treatment, while the Q8W diplopia comparisons did not meet the nominal significance threshold. The source describes planned at-home autoinjector administration as a potential lower-burden delivery option; the reported results are top-line data from an investigational treatment.

Conclusion

In REVEAL-1, elegrobart met the primary endpoint of proptosis response at week 24, with response observed in both dosing groups. Diplopia and safety outcomes varied by dosing schedule, and the source reports that most adverse events were mild.