Telitacicept in phase 2b trial shows promising efficacy and safety profile for active SLE patients

Despite the approval of biological therapies like belimumab and anifrolumab for treating active systemic lupus erythematosus (SLE), there is a critical gap in the available treatments, with improved efficacy and safety. Addressing this need, a recently published phase 2 trial in the Annals of the Rheumatic Diseases sheds light on the promising efficacy and favorable safety profile of telitacicept among SLE patients. 

The randomized, double-blind, and placebo-controlled clinical trial, led by Wu et al., involved adult patients diagnosed with active SLE, with a total enrollment of 249 individuals across 29 hospitals in China. The participants were evenly allocated into four groups: those receiving subcutaneous telitacicept at 80 mg (n=62), 160 mg (n=63), 240 mg (n=62), or a placebo (n=62) once weekly, in addition to their standard therapy. The primary objective was to ascertain the proportion of patients achieving a notable response, defined by the SLE Responder Index 4 (SRI-4), by the 48th week. 

Study results revealed a significant response rate in the telitacicept groups compared to the placebo. By the 48th week, the 240 mg telitacicept group exhibited the highest response rate at 75.8%, followed by 68.3% in the 160 mg group, 71% in the 80 mg group, and notably lower at 33.9% in the placebo group (P <0.001). Secondary endpoints also indicated noteworthy treatment responses, including a reduction of at least four points on the Systemic Lupus Erythematosus Disease Activity Index, stability in the Physician’s Global Assessment score, and a reduction in glucocorticoid dosage, particularly observed in the 240 mg group. Furthermore, the study demonstrated that telitacicept was well-tolerated, with a similar incidence of adverse events and serious adverse events between the telitacicept and placebo groups. 

 B cells play a central role in SLE and other autoimmune diseases, modulated by B lymphocyte stimulator (BLyS), a critical regulator influencing B cell development, function, and survival. BLyS engages with multiple B cell surface receptors, including transmembrane activator and CAML interactor (TACI), B cell maturation antigen (BCMA), and BAFF. Elevated BLyS levels are observed in autoimmune conditions, including SLE. Despite the relevance of belimumab, a monoclonal antibody targeting BLyS, in SLE treatment, some patients exhibit inadequate responses. Another pertinent protein, APRIL, influences B cell activities through TACI and BCMA receptors. The combined inhibition of both BLyS and APRIL holds promise in substantially reducing autoantibody production in SLE. Telitacicept, a novel fusion protein, effectively blocks both BLyS and APRIL by binding to the extracellular BLyS/APRIL-binding domain of the TACI receptor and the Fc fragment of human IgG1. 

The recently conducted phase 2 trial on telitacicept has demonstrated its efficacy and favorable safety profile in individuals with SLE, presenting a novel avenue for the treatment of active SLE patients. These results strongly advocate for further comprehensive studies involving diverse populations and larger sample size to further understand the potential of telitacicept in the management of SLE. 


Wu D, Li J, Xu D, Merrill JT, van Vollenhoven RF, Liu Y, et al. Telitacicept in patients with active systemic lupus erythematosus: results of a phase 2b, randomized, double-blind, placebo-controlled trial. Ann Rheum Dis. 2023 Dec 21;ard-2023-224854.