Safety and Efficacy of Evobrutinib, a Bruton's Tyrosine Kinase Inhibitorin Relapsing Multiple Sclerosis Over 2.5 Years of The Open-Label Extension to a Phase II Trial
Neurology
; 98(18 SUPPL), 2022.
Article
in English
| EMBASE | ID: covidwho-1925395
ABSTRACT
Objective:
Report the safety and efficacy of evobrutinib over 2.5 years in an open-label extension (OLE).Background:
Evobrutinib, a covalent, blood-brain barrier-penetrating Bruton's tyrosine kinase inhibitor, was well tolerated and effective at reducing gadolinium-enhancing lesions in a double-blind, randomized phase II trial in patients with relapsing multiple sclerosis (pwRMS;NCT02975349). Design/Methods:
In the 48-week (W) double-blind period (DBP), pwRMS (n=267) received placebo (switched to evobrutinib 25mg once-daily at 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. The latest available OLE data are now reported.Results:
Of 267 DBP patients, 213 (80%) entered the OLE;164 (61%) completed ≥132W of OLE treatment. Treatment-emergent adverse events (TEAEs) were reported by 165/213 patients (77.5%);59 (27.7%) had a treatment-related TEAE. Six serious TEAEs were deemed treatment-related. Severe/opportunistic infections (≥Grade 3) were reported by 9/213 patients (4.2%);3 were fatal (Covid-19 pneumonia [n=2] and E. coli sepsis [n=1];not considered treatment-related). At OLE W120, most patients had IgG (91%), IgA (88%) and IgM (82%) within normal ranges. Overall mean CD19+ B cells levels were 0.218×10 cells/mL (OLE baseline) and 0.122×10 cells/mL (OLE W96). ALT/AST elevations were observed only in patients previously receiving DMF/evobrutinib 25mg and occurred within 12W of OLE initiation. Amylase/lipase increases occurred in 6 (2.8%)/24 (11.3%) patients, but without clinical signs and symptoms. Based on all available OLE data, ARR was 0.12 (95%CI 0.07-0.20) for patients receiving 75mg twice-daily in the DBP. 6 6Conclusions:
Evobrutinib safety and efficacy data over 2.5 years in pwRMS continue to show acceptable tolerability, with no new safety signals, and maintained efficacy.
amylase; Bruton tyrosine kinase; Bruton tyrosine kinase inhibitor; dimethyl fumarate; endogenous compound; evobrutinib; gadolinium; immunoglobulin A; immunoglobulin G; immunoglobulin M; placebo; triacylglycerol lipase; adult; aspartate aminotransferase level; B lymphocyte; blood brain barrier; cell level; clinical trial; conference abstract; controlled study; coronavirus disease 2019; covalent bond; double blind procedure; drug combination; drug efficacy; drug safety; drug therapy; drug tolerability; Escherichia coli; female; human; human cell; major clinical study; male; multiple sclerosis; nonhuman; opportunistic infection; phase 2 clinical trial; randomized controlled trial; sepsis; signal transduction
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Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Randomized controlled trials
Language:
English
Journal:
Neurology
Year:
2022
Document Type:
Article
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