Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Arthritis Rheumatol. 2021;73(10):183–46

Despite evidence of strong pathway inhibition, findings from a Phase 2 study of patients with moderate-to-severe SLE indicate that fenebrutinib did not demonstrate a treatment benefit over placebo.

With only one biologic being approved in the last 60 years, there is a current need for effective therapies in SLE. To this end, Isenberg, et al. assessed the efficacy, safety, and pharmacodynamics of the noncovalent, oral, and highly selective inhibitor of BTK, fenebrutinib, in SLE.

By week 48, patients treated with fenebrutinib had reduced levels of a BTK-dependent plasmablast RNA signature, anti-double-stranded DNA autoantibodies, total IgG, and IgM, as well as increased complement C4 levels, all relative to placebo. However, the primary end point, SRI-4 response, was not met.