Endocrine Abstracts

JOINT1512

Introduction: Thyrotropin receptor autoantibodies (TRAb) cause Graves’ hyperthyroidism (GH) and its extrathyroidal manifestations. Batoclimab, a neonatal fragment crystallizable receptor (FcRn) inhibitor, reduces IgG levels, including TRAb.

Objective: To describe serological and clinical outcomes from a phase 2a, proof-of-concept, open-label, single-center study evaluating batoclimab in patients with GH.

Methods: Eligible patients had serologically confirmed GH and elevated TRAb and were hyperthyroid despite ongoing therapy with moderate-to-high dose anti-thyroid drugs (ATD) for ≥12 weeks. Batoclimab was administered via subcutaneous injection at a dose of 680 mg weekly for 12 weeks, followed by 340 mg weekly for 12 weeks. Key endpoints included the proportion of patients who achieved FT3 and FT4 normalization (serum levels ≤upper limit of normal [ULN] and ≥lower limit of normal [LLN]) or FT3 and/or FT4 <LLN without increase in ATD dose; proportion of patients with FT3 and FT4 normalization or FT3 and/or FT4<LLN and ATD dose ≤50% of baseline; and reductions in TRAb.

Results: As of the data cutoff, 25 patients either completed Week 24 (n = 23) or discontinued prematurely due to non-treatment-related reasons (n = 2). Eighty percent (20/25) had pre-existing Graves’ orbitopathy. By Week 2, 15/25 (60%) patients achieved FT3 and FT4 ≤ULN, without an increase in ATD. After 12 weeks of high-dose (680 mg) batoclimab, 19/25 (76%) patients had FT3 and FT4 ≤ULN without an increase in ATD, including 14/25 (56%) who were off ATD and 5/25 (20%) who achieved normal thyroid-stimulating hormone levels. At Week 24, after 12 weeks of lower-dose (340 mg) batoclimab, 17/25 (68%) patients had FT3 and FT4 ≤ULN without an increase in ATD, including 9/25 (36%) who were off ATD. Mean TRAb decreased from baseline by 74% and 70% at Weeks 12 and 24, respectively, and 5/25 (20%) and 3/25 (12%) patients achieved seroconversion (TRAb-negative), respectively. Improvement from baseline in ophthalmic parameters (eg, proptosis, lid aperture, clinical activity score) and reduction in ultrasound-assessed thyroid volume were also observed. Batoclimab was well-tolerated, with all adverse events being mild-to-moderate in severity; no new safety signals were observed.

Conclusion: Subcutaneous batoclimab very rapidly normalized FT3 and FT4 in most patients. By Week 12, more than half of patients had both T3 and T4 ≤ULN and were off ATD. Batoclimab also improved extrathyroidal signs. These data are the first clinical evidence that FcRn inhibition may be effective for treating Graves’ hyperthyroidism.