Safety/efficacy of evobrutinib, a Bruton's tyrosine kinase inhibitor, 2.5 years into Phase II MS open-label extension

ABSTRACT

Background and aims: Evobrutinib, a Bruton's tyrosine kinase inhibitor, was well tolerated and effective in a double-blind, randomised Phase II trial in patients with relapsing multiple sclerosis (pwRMS;NCT02975349). Objective: report evobrutinib safety and efficacy data 2.5 years into an open-label extension (OLE). Methods: In the 48-week (W) double-blind period (DBP), pwRMS (n=267) received placebo (switched to evobrutinib 25mg once-daily, W24), evobrutinib 25mg once-daily, 75mg once-daily, or 75mg twice-daily, or open-label dimethyl fumarate (DMF;240mg twice-daily). At W48 patients could enter the OLE (DMF 4-8W washout);evobrutinib 75mg once-daily (median ∼48W) then 75mg twice-daily. We report the latest available OLE data. Results: Of 267 DBP patients, 213 (80%) entered the OLE;164 (61%) completed ≥132W OLE treatment. Treatmentemergent adverse events (TEAEs) were reported by 165/213 patients (77.5%);59 (27.7%) had a treatment-related TEAE (six were serious;Table). Severe/opportunistic infections (≥Grade 3) were reported by 9/213 patients (4.2%);three (not treatment related;Covid pneumonia [n=2]) were fatal. Most patients had normal IgG (91%), IgA (88%) and IgM (82%) levels (OLE W120). Mean CD19+ B cells levels were 0.218x106cells/mL (OLE baseline) and 0.122x106cells/ mL (OLE W96). ALT/AST elevations only occurred in patients previously receiving DMF/evobrutinib 25mg, and within 12W of OLE initiation. Amylase/lipase increases occurred in 6 (2.8%)/24 (11.3%) patients, without clinical signs and symptoms. ARR, for patients receiving 75mg twice-daily in the DBP, was 0.12 (95%CI 0.07-0.20 [all available OLE data]). Conclusion: Evobrutinib safety and efficacy data over 2.5 years shows acceptable tolerability, no new safety signals and maintained efficacy in pwRMS.