Objective
To evaluate multi-dimensional response with claseprubart based on patient and clinician assessments.
Background
The classical complement pathway plays a significant role in acetylcholine receptor-positive generalized Myasthenia Gravis (gMG) pathology. Claseprubart is an investigational, clinical-stage, potent monoclonal antibody engineered to selectively target the classical complement pathway that is implicated in generalized gMG, by selectively inhibiting activated C1s protein. Clinical benefit of claseprubart in gMG may be best supported by improvements across multiple validated scales to capture multi-dimensional improvement beyond single-scale analyses.
Design/methods
AChR+ gMG patients treated with 300mg claseprubart subcutaneously once every 2 weeks in the MaGic study (NCT06282159) – a global Phase 2, randomized, double-blind, placebo-controlled trial – were analyzed for responses based on multiple assessments compared to placebo. p-values are one-sided, with nominal significance assessed at an alpha of 0.1. The definition of response was set based on MG-ADL and QMG. Endpoints include proportion of patients who were dual responders based on MG-ADL and QMG at Week 13; time to response, and proportion of responders sustaining response for ≥6 weeks.
Results
63% of claseprubart patients had dual response improvement in MG-ADL≥3, QMG ≥4, vs 14% placebo (OR 29.00; p=0.0006). Dual responders were seen as early as Week 1. Median time to response Week 3. All the claseprubart-treated patients with dual response at Week 13 had maintained response ≥6 weeks.
Conclusions
Claseprubart-treated patients were more likely to achieve multi-dimensional response than placebo. Responses emerged early and were sustained, confirming rapid, robust, and durable benefit from claseprubart across functional and quantitative measures from both patient and clinician perspectives.