Fenebrutinib Demonstrates Strong Efficacy, Favorable Safety in FENhance MS Trials: Jacqueline Nicholas, MD

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“The real clinical implication is that [fenebrutinib] has the potential to be a drug that is considered high efficacy in shutting down inflammation within multiple sclerosis, but not only that, to also get at a mechanism of targeting progression so that we're impacting our patients in a dual way that we haven't been able to do as well historically."

The phase 3 FENhance 1 (NCT04586010) and FENhance 2 (NCT04586023) trials evaluated fenebrutinib, an investigational Bruton tyrosine kinase (BTK) inhibitor, in adults with relapsing forms of multiple sclerosis (MS). Conducted across multiple international centers, the parallel studies compared fenebrutinib with teriflunomide, an approved disease-modifying therapy, to assess its efficacy and safety in controlling disease activity. The primary endpoint in both trials was annualized relapse rate (ARR), with secondary outcomes including MRI measures of disease activity, disability progression, and safety assessments. Investigators also examined the effects of treatment on gadolinium-enhancing lesions and new or enlarging T2 lesions, key radiographic markers of inflammatory disease activity.

Participants enrolled in the FENhance studies were randomized to receive either fenebrutinib or teriflunomide and were followed longitudinally to assess clinical, radiographic, and safety outcomes. Disease activity was evaluated through regular neurological assessments, relapse monitoring, and serial MRI scans, allowing investigators to quantify inflammatory lesion burden and changes over time. Disability outcomes were measured using established clinical scales, while laboratory testing and adverse event monitoring were incorporated throughout the study period to characterize the safety profile of treatment. This study design enabled researchers to evaluate the effects of fenebrutinib across multiple dimensions of relapsing MS, including relapse prevention, radiographic disease control, disability progression, and treatment tolerability.

Findings from both studies, presented at the 2026 Consortium of Multiple Sclerosis Centers (CMSC) annual meeting, held May 27-29 in Charlotte, North Carolina, demonstrated that fenebrutinib significantly reduced ARR and suppressed MRI markers of disease activity in patients with relapsing multiple sclerosis compared with teriflunomide. Presented by Jacqueline Nicholas, MD, neuroimmunologist and director at OhioHealth MS Center, the data also suggested potential benefits on disability progression while reinforcing the therapy's manageable safety profile, including findings related to liver enzyme monitoring. During the meeting, NeurologyLive sat down with Nicholas to gain further insight into the clinical implications of these findings.

In the interview, the speaker highlighted the robust efficacy findings from the FENhance 1 and 2 studies of fenebrutinib, emphasizing its statistically significant reduction in ARR and near-complete suppression of gadolinium-enhancing lesions. The discussion also explored the therapy's impact on MRI outcomes, including significant reductions in new or enlarging T2 lesions, as well as signals suggesting benefits on disability progression across both relapsing and progressive forms of multiple sclerosis. Furthermore, Nicholas also outlined the broader clinical implications of these findings, noting fenebrutinib's potential to function as a high-efficacy treatment capable of both controlling inflammatory disease activity and targeting mechanisms of progression.