Orelabrutinib for active SLE: A phase Ib/IIa study

Results from a multicenter, double-blind, randomized, placebo-controlled, phase Ib/IIa study (NCT04305197) evaluating oral orelabrutinib 50 mg (n = 15), 80 mg (n = 15), or 100 mg (n = 16) once daily (QD) vs placebo (n = 14) for 12 weeks in adults with active systemic lupus erythematosus (SLE) receiving standard-of-care (SoC) therapy were published in the Journal of Autoimmunity by Li et al. Eligible patients had SLE for ≥6 months and met ≥4 of the 11 revised 1997 American College of Rheumatology (ACR) classification criteria. The primary endpoint was safety and tolerability, assessed by treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), vital signs, electrocardiogram (ECG), and laboratory findings.

Key data: TEAEs occurred in 90% of patients overall, including 80%, 93%, 100%, and 86% of patients in the orelabrutinib 50 mg, 80 mg, 100 mg, and placebo groups, respectively. TRAEs occurred in 72% of patients overall, including 67%, 87%, 81%, and 50% of patients in the orelabrutinib 50 mg, 80 mg, 100 mg, and placebo groups, respectively. Treatment-related SAEs (TRSAEs) occurred only with orelabrutinib 80 mg (13%) and 100 mg (6%), with no deaths reported in any group. Among evaluable patients at Week 12, Systemic Lupus Erythematosus Responder Index (SRI)-4 response rates were 50%, 62%, and 64% with orelabrutinib 50 mg, 80 mg, and 100 mg, respectively, and 36% with placebo; SRI-6 response rates were 36%, 39%, 21%, and 7%, respectively.

Key learning: Orelabrutinib demonstrated an acceptable safety profile with preliminary signals of clinical activity in active SLE, supporting further evaluation in larger studies with longer follow-up to further determine efficacy and optimal dosing.