In a breakthrough for the treatment of systemic lupus erythematosus (SLE), a novel fusion protein, telitacicept, has shown significant promise in reducing disease activity and improving patient outcomes, according to a new phase 2b clinical trial. The study, which involved 249 adult patients with active SLE across 29 hospitals in China, found that telitacicept, when administered weekly, resulted in substantial improvement in disease markers, including the primary endpoint of the SLE Responder Index 4 (SRI-4).
The randomized, double-blind, placebo-controlled trial involved four groups of patients. Participants were randomly assigned to receive subcutaneous injections of telitacicept at one of three doses: 80 mg, 160 mg, or 240 mg, or a placebo, administered once a week in addition to their standard therapy. The trial found that telitacicept significantly outperformed placebo across all doses in achieving the primary endpoint, with 75.8% of patients in the 240 mg telitacicept group achieving an SRI-4 response at week 48, and 68.3% in the 160 mg group and 71.0% in the 80 mg group also showing positive responses. In contrast, only 33.9% of patients in the placebo group achieved an SRI-4 response (all p<0.001). Furthermore, secondary outcomes were significantly improved in the telitacicept-treated groups, particularly in the 240 mg cohort, which demonstrated a ≥4-point reduction in the SLEDAI score, no worsening of the Physician’s Global Assessment score, and a reduction in glucocorticoid use, a common marker of disease control in lupus patients.
Telitacicept targets and neutralizes the activity of two critical cell-signaling molecules, B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL). These molecules are pivotal in regulating the survival and differentiation of B cells, which play a central role in the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE). By binding to and inhibiting the activity of BLyS and APRIL, telitacicept reduces the development, survival, and activity of plasma cells and mature B cells. This leads to a reduction in the production of autoantibodies and modulates the immune system’s response, helping to decrease disease activity and inflammation in conditions like SLE.
A similar study conducted by Fan et al. reported that telitacicept is a novel recombinant fusion protein composed of the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and the Fc portion of human immunoglobulin G (IgG) (TACI-Fc). It was specifically designed to inhibit the activity of two cytokines—B-cell lymphocyte stimulator (BLyS), also known as B-cell activation factor (BAFF), and a proliferation-inducing ligand (APRIL)—which are both involved in B cell-mediated autoimmune diseases.
Telitacicept was found to be well tolerated, with the incidence of adverse events (AEs) and serious adverse events (SAEs) comparable between the telitacicept and placebo groups. The treatment did not introduce any new or unexpected safety concerns, reinforcing its potential as a safe and effective therapeutic option for patients with SLE.
The phase 2b trial results suggest that telitacicept holds promise as a new treatment for active SLE, demonstrating significant improvements in disease activity and tolerability compared to placebo. These findings support further investigation in larger, more diverse populations and long-term studies to confirm its benefits and safety, marking an important step toward developing more targeted therapies for this challenging autoimmune disease.
Reference
- 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, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2024 Mar 12;83(4):475–87.
- Dhillon S. Telitacicept: First Approval. Drugs. 2021 Sep;81(14):1671–5.
- Fan Y, Gao D, Zhang Z. Telitacicept, a novel humanized, recombinant TACI-Fc fusion protein, for the treatment of systemic lupus erythematosus. Drugs Today (Barc). 2022 Jan;58(1):23–32.