Orelabrutinib in moderate-to-severe SLE: Phase IIb study results

Results from a randomized, double-blind, placebo-controlled phase IIb study evaluating orelabrutinib in patients with moderate-to-severe systemic lupus erythematosus (SLE) were presented by Li at the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress, June 3–6, 2026, London, UK. A total of 187 patients were randomized to receive oral orelabrutinib 50 mg once daily (QD; n = 60), 75 mg QD (n = 63), or placebo (n = 64). The primary endpoint was the SLE Responder Index-4 (SRI-4) response rate at Week 48.

Key data: At Week 48, a greater proportion of patients receiving orelabrutinib 75 mg vs placebo achieved SRI-4 responses (57.1% vs 34.4%; p = 0.01), with significant improvements observed from Week 20. A greater proportion of patients receiving orelabrutinib 75 mg vs placebo also achieved SRI-6 responses at Week 48 (44.4% vs 25.0%; p = 0.015), with significant improvements observed from Week 8. British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) responses also favored orelabrutinib 75 mg vs placebo at Week 48 (33.3% vs 15.6%; p = 0.011). Glucocorticoid dose reductions to ≤7.5 mg/day were achieved by a greater proportion of patients receiving orelabrutinib 75 mg vs placebo (71.1% vs 43.6%; p = 0.015). The safety profile of orelabrutinib was favorable and similar between the 50 mg and 75 mg groups. Treatment-emergent adverse events (TEAEs) occurred in 98.4% of patients receiving orelabrutinib 75 mg vs 90.6% of patients receiving placebo, with treatment-emergent serious adverse events (TESAEs) reported in 19.0% vs 4.7% of patients. 

Key learning: Orelabrutinib demonstrated significant reductions in disease activity and glucocorticoid dose at Week 48, with a manageable safety profile in patients with moderate-to-severe SLE.