Telitacicept Improves Sjögren Symptoms Over Placebo in Phase 3 Trial

Telitacicept (Vor Bio) improved symptoms of Sjögren disease (SjD) compared to placebo through 48 weeks, in both the 80 mg and 160 mg doses assessed, with a favorable safety profile.1

These findings, from a randomized, double-blind, placebo-controlled, phase 3 study (NCT05673993) conducted across 79 centers in China, were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Lin Qiao, MD, Peking Union Medical College Hospital, Beijing, China.

“SjD is a chronic systemic autoimmune disease. B-cells play an important role in the pathogenesis,” Qiao and colleagues wrote in their poster.1 “Telitacicept, a novel fusion protein, dually inhibits BAFF and APRIL, leading to upstream modulation of B-cell survival, downstream reduction of pathogenic antibodies, and re-balancing of dysregulated B-cell immunity. Telitacicept has previously demonstrated efficacy and safety in a phase 2 study in SjD.”

The study enrolled participants aged 18–70 years who met the 2016 ACR/EULAR criteria for SjD and who were anti-SSA antibody positive with ESSDAI score ≥5. A total of 381 eligible participants were randomly assigned to telitacicept 160 mg (N=127), telitacicept 80 mg (N=127), and placebo (N=127). One participant in the telitacicept 80 mg group who prematurely withdrew before receiving study treatment was excluded from the estimand population and safety set. The study primarily assessed change from baseline in ESSDAI score at Week 24, with secondary endpoints assessing change from baseline in ESSDAI score at Week 48, the proportion of participants with ≥3-point reduction from baseline in ESSDAI score; those with ESSDAI 100 score <5; those with ≥1-point or ≥15% reduction from baseline in ESSPRI; and change from baseline in ESSPRI total score (all at Week 24 and Week 48). The study also assessed the proportion of STAR responders, adverse events (AEs) and immunological parameters.1

At week 24, patients receiving telitacicept 160 mg and 80 mg achieved significantly greater improvements in ESSDAI scores compared with placebo, with least squares mean (LSM) changes of −4.4 (95% CI, −5.0 to −3.8) and −3.0 (95% CI, −3.6 to −2.4), respectively, versus −0.6 (95% CI, −1.2 to −0.0) for placebo (P <.0001 for both). The LS mean differences from placebo were −3.8 (95% CI, −4.6 to −3.0) and −2.4 (95% CI, −3.2 to −1.6), respectively. At week 48, reductions in ESSDAI remained robust for telitacicept 160 mg (LSM, −4.6; 95% CI, −5.3 to −4.0) and 80 mg (LSM, −3.2; 95% CI, −3.9 to −2.6) versus −0.4 (95% CI, −1.1 to 0.2) with placebo (P <.0001 for both).1

Across key secondary endpoints, higher proportions of participants receiving telitacicept achieved clinically meaningful responses. At week 48, a ≥3-point ESSDAI reduction occurred in 73.0% of patients in the 160 mg group and 49.1% in the 80 mg group versus 16.5% with placebo, with differences of 56.4% (95% CI, 45.7%–67.1%; P <.0001) and 32.7% (95% CI, 21.5%–43.9%; P <.0001). Similar trends were seen for achieving ESSDAI <5 points, ≥1-point or ≥15% ESSPRI reduction, and STAR response. At week 48, LS mean change in ESSPRI was −2.56 (95% CI, −2.84 to −2.27) with telitacicept 160 mg and −1.74 (95% CI, −2.03 to −1.46) with 80 mg, compared with −0.41 (95% CI, −0.69 to −0.13) for placebo (LS mean differences −2.15 and −1.34, respectively; P <.0001 for both).1

Treatment-emergent AEs (TEAEs) were reported in 96.1% of the 160 mg group, 94.4% of the 80 mg group, and 88.2% of the placebo group. Treatment-related AEs (TRAEs) occurred in 84.3% and 84.1% of the telitacicept 160 mg and 80 mg groups, respectively, versus 58.3% with placebo. Serious TEAEs were infrequent across groups (80 mg, 8.7%; 160 mg, 11.1%; placebo, 7.9%, respectively), as were treatment-related serious AEs (80 mg, 1.6%; 160 mg, 4.0%; placebo, 3.1%). Severe TEAEs occurred in ≤4.0% of participants, and no deaths were reported. The most common TEAEs included upper respiratory tract infection (telitacicept, 63.0%–67.5%; placebo, 58.3%), injection site reaction (telitacicept, 41.7%–40.5%; placebo, 3.9%), hepatic function abnormal (telitacicept; 5.5%–12.7%; placebo, 5.5%), and pyrexia (telitacicept, 3.1%–11.1%; placebo, 3.1%).1

“The primary efficacy endpoint was reached in this study,” Qiao and colleagues concluded.1 “Compared with placebo, both telitacicept 160 mg and 80 mg demonstrated consistent clinical symptom improvement through 48 weeks and a favorable safety profile; greater improvements were observed in the telitacicept 160 mg group.”

Telitacicept is also being investigated for treating systemic lupus erythematosus (SLE) and recently demonstrated markedly higher response rates compared to placebo in addition to standard therapy in a phase 3 trial, although accordingly higher rates of AEs were also observed.2

At week 52, significantly more participants receiving telitacicept (67.1%) had a modified SRI-4 response than those receiving placebo (32.7%; adjusted difference, 34.5%; 95% CI, 24.3-44.7; P <.001). Furthermore, 70.1% of the telitacicept group compared to 40.5% of the placebo group achieved a reduction of at least 4 points from baseline in the SELENA-SLEDAI score (difference, 29.6%; 95% CI, 13.1-46.1).2

Investigators did observe significant differences in the safety profiles between the placebo and telitacicept groups. The telitacicept group had a higher incidence (74.9%) of AEs considered related to treatment then placebo (50%), including upper respiratory tract infections (31.7% vs. 19.0%), a reduced serum IgG level (15.6% vs. 1.2%), reduced serum IgM levels (15.0% vs. 0.6%), and injection-site reactions (12.6% vs. 0.6%).2

References

1. Du X, Zhang S, Qiao L, et al. LB11: Efficacy and Safety of Telitacicept in Patients with Sjögren's Disease: Results from a Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Clinical Study. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB11.

2. van Vollenhoven RF, Wang L, Merrill JT, et al. A Phase 3 Trial of Telitacicept for Systemic Lupus Erythematosus. N Engl J Med. 2025;393(15):1475-1485. doi:10.1056/NEJMoa2414719