To assess efficacy and safety of telitacicept in a phase 3, multicenter, randomized, placebo-controlled study in patients with generalized myasthenia gravis (gMG).

In 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.

Eligible 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, then entered a 24-week, open-label period (weekly telitacicept [240 mg]). The primary endpoint was change in MG-ADL at Week 24. Secondary endpoints included change in QMG, and the proportion of patients with ≥3-point reduction in MG-ADL and ≥5-point reduction in QMG. Immunological and safety parameters were assessed.

114 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 (p<0.001). 98.1% and 12.0% of telitacicept 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 (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.

Telitacicept demonstrated clinically meaningful efficacy and a safety profile consistent with data from studies in various indications. The 24-week, open-label period is ongoing.