Twice-daily evobrutinib linked to lower relapse, less clinical worsening after 5 years

Key takeaways:

• The study evaluated 5-year outcomes of 124 individuals in an open-label extension of a phase 2 trial.
• The results demonstrate a “sustained benefit” of treatment with evobrutinib, researchers wrote.

Treatment with evobrutinib in continuous, twice-daily dosing provided the lowest relapse rate and highest arrest of clinical worsening after 5 years in those with relapsing multiple sclerosis, according to data presented at ECTRIMS 2023.

“Evobrutinib is a highly selective, central nervous system-penetrant, covalent Bruton’s tyrosine kinase inhibitor,” Xavier Montalban, MD, PhD, chair of the department of neurology-neuroimmunology at Vall d’Hebron, University Hospital, Barcelona, and colleagues wrote.

Montalban and colleagues aimed to evaluate the long-term treatment effect of evobrutinib on safety and efficacy in those with relapsing MS up to 5 years into the open-label extension of a phase 2 clinical trial.

For the 48-week double-blind period (DBP), 267 individuals were randomized to placebo (switched to 25 mg evobrutinib once per day after week 24), evobrutinib (Merck) (25 mg or 75 mg once daily, or 75 mg twice daily in a fasted state), or open-label reference treatment with dimethyl fumarate.

Among the evobrutinib-treated patients in the DBP, 164 entered the OLE and received 75 mg of once-daily evobrutinib before switching to 75 mg twice daily (n = 151). Achieving no evidence of clinical worsening (NEcW) was defined as no qualified relapses and no 12-week confirmed disability progression measured by a worsening score on the Expanded Disability Status Scale.

Of the 164 evobrutinib-treated patients who entered the OLE, 124 reached the 5-year mark, Montalban and colleagues reported.

In year 5 of the OLE, 108 of 124 enrollees had NEcW, indicating the sustained long-term benefit of a twice-daily regimen. The proportion of patients achieving NEcW who initially received low doses in the DBP increased from 70.8% and 74.5% in the DBP to 90.0% and 92.6% in OLE year 5 while receiving 75 mg evobrutinib twice daily, respectively.

In the DBP, the lowest annualized relapse rate was observed in the twice-daily 75 mg evobrutinib arm (week 48: 0.11; other treatment arms ranged from 0.25 to 0.52), while the proportion of patients achieving NEcW was higher with twice-daily 75 mg evobrutinib (41 of 46) compared with the switched cohort (34 of 48).

Adverse events were reported in 142 of 164 participants, with 43 of 164 reporting treatment-related events and four of 164 logging serious treatment-emergent adverse events.

“Notably, nine out of 10 patients maintained [no evidence of clinical worsening] in year 5, demonstrating the sustained benefit of EVO treatment,” Montalban and colleagues wrote. “The safety profile remains consistent with that previously reported.”