2025 American Academy of Neurology Abstract Website

Jiwon Oh¹, Jelena Drulovic², Michal Dufek³, Hrvoje Budincevic⁴, Mario Habek⁵, Maresa Caunt⁶, Malgorzata Sierzega⁷, David Clayton⁶, Ying-Fang Chen⁶, Jack Ratchford⁶, Alexandra Goodyear⁶, Amit Bar-Or⁸
¹St. Michael's Hospital, ²University Clinical Center of Serbia, ³St. Anne's University Hospital Brno, ⁴Solmed Polyclinic and Sveti Duh University Hospital, ⁵University Hospital Center Zagreb, ⁶Genentech, Inc., ⁷F. Hoffmann-La Roche Ltd, ⁸University of Pennsylvania

Objective:

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

Background:

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.

Design/Methods:

FENopta participants received fenebrutinib 200 mg orally twice daily or placebo during the double-blind treatment period (DBTP), and all received fenebrutinib during the OLE. Disease activity was evaluated through protocol-defined relapses and brain MRI at OLE Week 48. Safety was also monitored.

Results:

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.

Conclusions:

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.