We report long-term safety data from an ongoing open-label extension (OLE) in patients treated ≥60 OLE weeks or discontinuing early.

In a 48-week Phase II study NCT02975349, in patients with relapsing multiple sclerosis, evobrutinib was generally well-tolerated.

During the double-blind period (DBP), 213 patients were randomized to evobrutinib 25mg QD, 75mg QD, 75mg BID or placebo for 24 weeks, continuing until 48 weeks, except placebo patients, who switched to evobrutinib 25mg QD. At Week 48, patients could enter the OLE. Treatment was evobrutinib 75mg QD (median ≈48 weeks) before switching to 75mg BID. Treatment-emergent adverse events (TEAEs) were assessed throughout the OLE, immune cells at OLE Week 48, and Ig levels at OLE Weeks 24 and 48.

TEAEs occurred in 107 (65.2%) of OLE patients (47.6% mild, 36.0% moderate, 7.9% serious), balanced across previous DBP groups; no deaths occurred. Transient aminotransferase elevations in the DBP were not observed in OLE patients continuing evobrutinib. CD19+ B cell counts decreased versus DBP baseline in all DBP evobrutinib groups, although mean values stayed in normal range, with no changes in memory B cell, T cell or NK cell counts, and no relevant change in IgG levels versus DBP baseline. Mean IgA and IgM levels increased and decreased, respectively, versus DBP baseline, but were within normal ranges. Immune cell and immunoglobulin changes following long-term treatment with evobrutinib in the OLE were consistent with those reported for the DBP. Evobrutinib did not appear associated with enhanced infection risk during the DBP or OLE.