The classical complement pathway plays a significant role in the pathogenesis of gMG. Claseprubart is a monoclonal antibody that targets the classical pathway by inhibiting active C1s (aC1s). 

MaGic (NCT06282159) is a randomized, double-blind, placebo-controlled Phase 2 study.   65 participants with AChR+ gMG were randomized 1:1:1 to receive: claseprubart 300mg (Q2W), claseprubart 600 mg (Q2W), or placebo for 13 weeks, followed by a 52-week open-label extension and 40-week safety follow-up. Endpoints at 13 weeks included safety, tolerability, efficacy (MG activities of daily living (MG-ADL), Quantitative MG score (QMG), Minimal Symptom Expression (MSE) and MG Composite scale (MGC).

Claseprubart was well tolerated with no serious adverse events, no serious bacterial infections, and no autoimmune activation. Injection site reactions were infrequent and mild to moderate. At Week 13, claseprubart improved MG-ADL by 4.6 (p=0.0113) for 300mg, 5.4 (p=0.0006) for 600mg, and 2.8 for placebo (no significant difference between active treatment arms). Significant improvement in MG-ADL was observed as early as Week 1. At Week 13, claseprubart 300mg improved QMG by 4.4 (p=0.0144), claseprubart 600mg by 4.5 (p=0.0111), and 2.0 for placebo. MSE was achieved by 37% (300mg) and 27% (600 mg) versus 14% for placebo. MGC for 300 mg was 8.7 (p=0.0008), 8.6 (p=0.0008) for 600 mg versus 3.1 for placebo.

With a favorable safety profile, claseprubart demonstrated rapid, statistically significant, and clinically meaningful improvements in MG-ADL, QMG, MGC.