Effect of Evobrutinib, a Bruton's Tyrosine Kinase Inhibitor, on Patient-Reported Vitality and Mental Health in Patients with Relapsing Multiple Sclerosis in a Phase 2 Trial

Evobrutinib (EVO), a highly selective, central nervous system-penetrant, covalent Bruton's tyrosine kinase inhibitor, has shown a significant effect on magnetic resonance imaging disease activity, sustained reduction in annualised relapse rate, and stable Expanded Disability Status Scale over >4.5 years (y) in patients (pts) with relapsing multiple sclerosis (PwRMS) in the Phase 2 study. Here, we report the effects of EVO on patient-reported outcomes comprising vitality (VT) and mental health (MH) known to impact PwRMS. In the 48 week (W), PwRMS (n=267) were randomised to placebo (PBO; switched to EVO 25mg once daily [QD] at W24), EVO (25mg QD, 75mg QD, or 75mg twice-daily [BID]; fasted), or open-label dimethyl fumarate (data not reported). Data for pts receiving PBO or EVO 25mg QD were pooled (PBO/EVO low dose). At W48, pts could enter the open-label extension (OLE). Descriptive summary statistics were used to assess changes from baseline (BL) and change categories. A Mixed Model for Repeated Measures was used for inferential analysis up to W48. Pts receiving EVO 75mg BID in the DBP showed significant improvements from BL to W48 versus (vs) PBO/EVO low dose for VT (mean±standard deviation [SD]: 3.2±8.8 vs −1.5±8.2, p=0.0032) and MH (3.4±11.2 vs −0.2±7.8, p=0.0365). Proportions of pts with a clinically meaningful improvement (≥5 points) from BL to W48 in VT and MH were numerically higher for EVO 75mg BID (32.6%, 37.0%) vs EVO 75mg QD (20.0%, 17.8%) and PBO/EVO low dose (17.4%, 25.6%). The inverse was true for worsening from BL to W48. EVO's treatment benefit on short form -36 (SF-36) scores was also seen in the OLE over 3.5y. After converting the SF-36 VT score to PROMIS Fatigue T-score, the change from BL to W48 showed significant improvement in pts treated with EVO 75mg BID vs PBO/EVO low dose (mean±SD: −2.7±7.0 vs 1.2±6.5, p=0.0021). EVO treatment resulted in significant and clinically meaningful improvements in both vitality and mental health with a greater benefit for EVO 75mg BID than lower doses. This benefit was also confirmed with conversion to PROMIS Fatigue T-scores providing early evidence, to be confirmed in Phase 3, that EVO may improve fatigue in PwRMS in addition to reducing disease activity.