Efficacy and safety of venanprubart, a BTLA agonist antibody, in patients with active systemic lupus erythematosus.

Objectives: This phase 2 study's objective was to determine whether venanprubart is superior to placebo for inducing remission of rash and/or arthritis in patients with at least moderately active systemic lupus erythematosus (SLE). Methods: Patients (N = 85) were randomly assigned in a 1:1 ratio to venanprubart (N = 42) or placebo (N = 43) in a multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group, 2-arm, phase 2 clinical trial. Treatment (450 mg venanprubart or placebo) was administered subcutaneously every 2 weeks along with standard of care for 24 weeks. The primary endpoint was remission of rash and/or arthritis as defined by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 at week (W) 24. Patients who discontinued the study or violated concomitant medication rules were imputed to nonresponse. Results: The study was terminated early based on lack of efficacy at the interim analysis. Venanprubart did not separate from placebo in inducing remission of rash and/or arthritis in 54 patients (26 on venanprubart; 28 on placebo) with SLE at W24. Patients treated with venanprubart were not significantly different from placebo for SLEDAI-4 response or Systemic Lupus Erythematosus Responder Index-4 response through W24. The number of treatment-emergent adverse events was similar across treatment groups. Patients treated with venanprubart reported 4 (9.5%) serious adverse events, whereas patients treated with placebo reported 1 (2.3%). No deaths occurred during the study. B and T lymphocyte attenuator receptor occupancy approached saturation on B cells, CD4+ T cells, and CD8+ T cells at all postrandomisation time points. Conclusions: Venanprubart did not demonstrate superiority to placebo in achieving remission of rash and/or arthritis. Venanprubart was safe and well tolerated.