In Brief | Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease
Estimated read time: 1 minute, 40 seconds
Originally Published: Dec 2023
Sourced: Journal of Clinical Endocrinology & Metabolism
Type of article: In Brief
MedED Catalogue Reference: MOIB007
Category: Ophthalmology
Cross Reference: Rare Diseases
Keywords: TED, thyroid eye disease, Graves disease, rare diseases, IgG antibodies,
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Originally published in the Journal of Clinical Endocrinology & Metabolism
Graves’ disease and the associated thyroid eye disease (TSH) are caused by IgG autoantibodies targeting the TSH receptors (TSH-R) on the thyroid gland and orbital target cells. The resulting activation of orbital fibroblasts via TSH-R- and IGF-1 receptor–mediated pathways results in inflammation and is accompanied by hydrophilic mucopolysaccharide production, tissue oedema, extraocular muscle swelling and the expansion of orbital connective tissue.
The neonatal fragment crystallizable receptor (FcRn) is a unique cellular receptor that interacts with IgG and albumin. Batoclimab (IMVT-1401) is a fully human monoclonal antibody that specifically binds to the IgG-binding site on FcRn. This competitive binding blocks FcRn from recycling IgG, reducing IgG levels in the body. This mechanism results in clinical benefits for patients with TED.
This study presents the first results of the proof-of-concept (POC) and randomized, double-blind, placebo-controlled trials of batoclimab conducted in patients with moderate-to-severe active TED.
- In the (POC) trial, 7 patients were given batoclimab 680 mg injections weekly for 2 weeks, then 340 mg injections weekly for 4 weeks. All 7 completed the treatment period; 5 completed the follow-up period.
- In the double-blind trial, 77 patients were randomly assigned to receive weekly batoclimab injections (at doses of 680 mg, 340 mg, or 255 mg) or a placebo for 12 weeks, with the allocation ratio being 2:2:1:2, respectively. Due to an unexpected rise in serum cholesterol levels, the trial was discontinued early, and the data from only 65 of the 77 patients were included in the final analysis.
In both trials, batoclimab significantly reduced pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001). However, in the randomized trial, there was no statistically significant difference in proptosis response between anticlimax and placebo at 12 weeks, despite significant differences at earlier time points. Furthermore, orbital muscle volume decreased (P < .03) at 12 weeks, and quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group.
Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.
Clinical Trial Reg Number: NCT03922321
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