Isenberg D, Furie R, Jones NS, et al. - An acceptable safety profile of fenebrutinib (GDC-0853: a noncovalent, oral, and highly selective inhibitor of Bruton’s tyrosine kinase (BTK)] was evident in systemic lupus erythematosus (SLE) patients, but it failed to meet the primary endpoint, SRI-4 (SLE Responder Index 4) response, despite evidence of strong pathway inhibition.

• This is a phase II, multicenter, randomized, placebo-controlled study.

• A total of 260 patients who had moderately to severely active SLE while on background standard therapy were included from 12 countries.

• They were randomized to receive placebo, fenebrutinib 150 mg once daily, or fenebrutinib 200 mg twice daily.

• At week 48, the SRI-4 response rates were 51% for fenebrutinib 150 mg once daily, 52% for fenebrutinib 200 mg twice daily, and 44% for placebo.

• Similar safety outcomes were evident across all arms, although fenebrutinib 200 mg twice daily more frequently had serious adverse events.

• Decreased levels of a BTK-dependent plasmablast RNA signature, anti–double-stranded DNA autoantibodies, total IgG, and IgM, as well as elevated complement C4 levels were found at week 48 in patients who received fenebrutinib vs placebo.