To present the design of a Phase 2a, proof-of-concept study evaluating safety, efficacy, and tolerability of empasiprubart add-on therapy in participants with generalized myasthenia gravis (gMG) who partially respond to efgartigimod. This is the first of multiple gMG regimens being assessed within a platform study.

gMG is driven by multiple mechanisms and manifests differently in each patient. In some, a single therapy may not sufficiently address all gMG mechanisms. Efgartigimod, an immunoglobulin G1 (IgG1) Fc fragment, alleviates gMG symptoms in many patients by blocking neonatal Fc receptor–mediated IgG recycling. Empasiprubart, an IgG1 antibody, selectively blocks complement C2. For patients with partial response to efgartigimod, empasiprubart add-on therapy could further improve outcomes.

The study consists of 3 parts (total duration, ~54 weeks). Part A: ~50 adult participants with acetylcholine receptor antibody-positive (AChR-Ab+) gMG receive 1 efgartigimod treatment cycle (4 once-weekly intravenous infusions followed by a 4-week treatment-free period). Part B: participants with partial response to efgartigimod (Myasthenia Gravis Activities of Daily Living [MG-ADL] improvements ≥2 with total remaining ≥5) receive 2 cycles of efgartigimod with intravenous empasiprubart coadministered at the first and last infusions of each cycle. Part C (safety follow-up): 4 additional cycles with efgartigimod monotherapy. Participants not meeting partial response criteria during Part A proceed to Part C.

Primary endpoints will evaluate safety and tolerability during Parts A and B. Secondary endpoints will evaluate efficacy, including MG-ADL.

Results of this study will provide proof-of-concept data on empasiprubart as an add-on therapy to efgartigimod for adults with AChR-Ab+ gMG.