To evaluate efficacy and safety of fenebrutinib in the FENopta open-label extension (OLE) study.

Fenebrutinib is a potent, highly selective, noncovalent, reversible Bruton’s tyrosine kinase inhibitor. In the Phase II FENopta study (NCT05119569), fenebrutinib reduced disease activity in relapsing multiple sclerosis (RMS) and demonstrated central nervous system penetrance. 

The OLE had 99 participants (65 fenebrutinib and 34 placebo during DBTP); 96 (97%) remain. Annualized relapse rate (ARR) was 0.04, and 96% of participants were relapse free. At OLE Week 48, the mean number of T1 gadolinium-enhancing (Gd+) lesions was 0.015 lesions per scan (n=67), and 99% of participants were free of Gd+ lesions. For fenebrutinib-treated, DBTP participants, mean T2 lesion volume decreased from baseline in the DBTP (−0.11 cm³ [95%CI: −0.43, 0.21]), which continued in the OLE (−0.33 cm³ [95%CI: −0.57, −0.095]). For placebo-treated, DBTP participants, mean T2 lesion volume increased in the DBTP (0.36 cm³ [95%CI: −0.081, 0.79]) but decreased after fenebrutinib treatment in the OLE (0.03 cm³ [95%CI: −0.28, 0.35]). Median change from baseline in Expanded Disability Status Scale (EDSS) at OLE Week 48 was 0 per arm. Serious adverse events (AEs) occurred in one participant (1%). Most common AEs were urinary tract infection (8%), COVID-19 (7%) and pharyngitis (5%). An asymptomatic alanine transaminase elevation occurred newly in one OLE participant (1%) that resolved.

Participants with RMS receiving fenebrutinib for 1 year had low ARR, stable EDSS and low MRI disease activity. Fenebrutinib maintained a favorable safety profile with high retention in the OLE. Three Phase III clinical trials are underway.