2025 Late-Breaking Science Abstracts

ObjectiveTo assess efficacy and safety of telitacicept in a phase 3, multicenter, randomized, placebo-controlled study in patients with generalized myasthenia gravis (gMG). BackgroundIn gMG, B cells produce autoantibodies targeting the acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK), disrupting neuromuscular transmission, leading to muscle weakness.Telitacicept, a novel fusion protein, inhibits B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), reducing B-cell activity, and showed efficacy and tolerability in a phase 2 study of patients with gMG. Design/MethodsEligible patients were adults with confirmed gMG diagnosis, on stable standard treatment, with positive serum AChR or MuSK antibody; Myasthenia Gravis Foundation of America (MGFA) class II, III, or IVa; Myasthenia Gravis-Activities of Daily Living (MG-ADL) score 6; and Quantitative Myasthenia Gravis (QMG) score 8.During a 24-week, double-blind period, patients were randomized 1: 1 to weekly subcutaneous telitacicept (240 mg) or placebo and then entered a 24-week, open-label period (weekly telitacicept [240 mg]).The primary end point was change in MG-ADL at week 24.Secondary end points included change in QMG, and the proportion of patients with 3-point reduction in MG-ADL and 5-point reduction in QMG.Immunologic and safety parameters were assessed. Results114 eligible patients were randomized (telitacicept, n = 57; placebo, n = 57).At week 24, change in MG-ADL was -6.4 and -1.6 with telitacicept and placebo, respectively (p < 0.001); change in QMG was -7.8 and -1.9, respectively (p < 0.001).98.1% and 12.0% of telitacicept-treated and placebo patients had 3-point reduction in MG-ADL, respectively (p < 0.001); 87.0% and 16.0% of patients had 5-point reduction in QMG, respectively (p < 0.001).Immunoglobulin (Ig) G, A, and M levels decreased with telitacicept and were unchanged with placebo.The most frequently reported adverse event with telitacicept was IgM decrease. ConclusionsTelitacicept demonstrated clinically a meaningful efficacy and safety profile consistent with data from studies in various indications.The 24week, open-label period is ongoing.