Update on long-term safety and efficacy of evobrutinib, a Bruton's tyrosine kinase inhibitor, over 5 years from an ongoing Phase 2 open-label extension

INTRODUCTION: Evobrutinib (EVO) is a highly selective, central nervous system-penetrant, covalent Bruton's tyrosine kinase inhibitor. The EVO efficacy and safety profile from the doubleblind period (DBP) of the Phase 2 trial in patients with relapsing multiple sclerosis (PwRMS) has remained stable in the ongoing open-label extension (OLE; NCT02975349). OBJECTIVES/AIMS: Evaluate the long-term treatment effect of EVO on efficacy (annualised relapse rate [ARR] and no evidence of clinical worsening [NEcW]) and safety in PwRMS up to Week (W) 240 (DBP W48 + OLE W192) of the Phase 2 OLE. METHODS: In the 48W DBP, PwRMS (n=267) were randomised to placebo (switched to EVO 25mg once-daily [QD] after W24), EVO (25mg QD, 75mg QD, or 75mg twice-daily [BID]; fasted), or open-label reference treatment with dimethyl fumarate (data not reported). Of the EVO-treated patients in the DBP, 164 entered the OLE and received EVO 75mg QD (mean[±SD] duration 50.6W[±6.0]), before switching to 75mg BID (n=151). Achieving NEcW was defined as no qualified relapses and no 12W confirmed disability progression (defined as confirmed worsening in Expanded Disability Status Scale). RESULTS: Of the 164 EVO-treated patients who entered the OLE, 124 (75.6%) had reached W240. In the DBP, the lowest ARR was observed with EVO 75mg BID (w48 : 0.11; other treatment arms ranged from 0.25-0.52). During the OLE, the pooled ARR was lower post-switch to EVO 75mg BID (0.11) vs pre-switch 75mg QD (0.20). In the DBP, the proportion of patients achieving NEcW was higher with 75mg BID (n=41/46, 89.1%) vs placebo/EVO 25mg QD (n=34/48, 70.8%). Overall, during OLE Year 5 (W192- 240), 108/124 (87.1%) patients had NEcW, indicating the sustained benefit of long-term BID dosing. The proportion of patients achieving NEcW who initially received low doses in the DBP (placebo/EVO 25mg QD; EVO 25mg QD) increased from 70.8% and 74.5% in the DBP to 90.0% and 92.6% in OLE Year 5 while receiving EVO 75mg BID, respectively. Treatment-emergent adverse events (TEAEs) were reported by 142/164 PwRMS (86.6%); 43/164 (26.2%) reported treatment-related TEAEs, 4/164 (2.4%) reported serious treatment-related TEAEs. CONCLUSION: The benefit of EVO treatment for over 5 years is demonstrated by the continued low relapse rate and high proportion of patients with no clinical worsening. Notably, 9 out of 10 patients maintained NEcW in Year 5, demonstrating the sustained benefit of EVO treatment. The safety profile remains consistent with that previously reported.