Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease

Area of Science:

• Immunology
• Endocrinology
• Ophthalmology

Background:

• Thyroid eye disease (TED) is an autoimmune condition driven by pathogenic thyrotropin receptor antibodies (TSH-R-Ab).
• Inhibition of the neonatal fragment crystallizable receptor (FcRn) is a strategy to reduce these pathogenic antibodies.

Purpose of the Study:

• To report the first clinical studies of batoclimab, an FcRn inhibitor, in patients with moderate-to-severe, active TED.
• To evaluate the safety and efficacy of batoclimab in reducing TSH-R-Ab and improving clinical outcomes in TED.

Main Methods:

• Proof-of-concept (POC) and randomized, double-blind, placebo-controlled trials were conducted across multiple centers.
• Patients received weekly subcutaneous injections of batoclimab at various doses or placebo for up to 12 weeks.
• Primary outcomes included changes in serum anti-TSH-R-Ab and total IgG (POC), and 12-week proptosis response (randomized trial).

Main Results:

• Both trials demonstrated marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels with batoclimab (P < .001).
• The randomized trial was terminated early due to increased cholesterol; however, analysis of available data showed no significant difference in proptosis response at 12 weeks compared to placebo.
• Significant decreases in orbital muscle volume (P < .03) and improvements in quality of life (appearance subscale, P < .03) were observed in the 680-mg group.

Conclusions:

• Batoclimab effectively reduces pathogenic TSH-R-Ab and total IgG in patients with TED.
• While not achieving statistical significance for proptosis at 12 weeks, batoclimab showed potential benefits in other measures and was generally well-tolerated.
• Further investigation of batoclimab as a potential therapy for TED is supported by these findings.