Promising Efficacy and Safety of Fenebrutinib in Relapsing Multiple Sclerosis (RMS): Insights from Phase II Study FENopta

• Fenebrutinib distinguishes itself from other BTK inhibitors through its unique reversible mechanism. It aims to treat relapsing and primary progressive MS. 
• Fenebrutinib treatment resulted in decreased new lesion activity and enhanced penetration into the cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients.

At the American Academy of Neurology conference 2024, findings from the ongoing Phase II study FENopta (NCT05119569), highlighted the efficacy and safety of fenebrutinib, a potent Bruton’s tyrosine kinase (BTK) inhibitor, in treating relapsing MS. Patients receiving fenebrutinib exhibited a significant reduction in total new T1 gadolinium-enhancing (Gd+) MRI lesions by 69%, along with decreased new/enlarging T2 (NET2) lesions by 74%, compared to those on placebo over 12 weeks. Additionally, fenebrutinib demonstrated notable penetration into CSF, with concentrations exceeding the active range observed in whole blood assays. Importantly, the treatment showed a favorable safety profile, with no serious adverse events reported.

Fenebrutinib stands apart from other BTK inhibitors due to its distinctive reversible mechanism. Roche, the developer of fenebrutinib, contends that this reversible action offers advantages in safety and efficacy over its competitors, particularly in the context of treating MS. By potentially allowing for greater control and modulation of BTK activity, the reversible mechanism could contribute to a more finely tuned therapeutic approach, potentially minimizing off-target effects and enhancing overall treatment outcomes.

Conclusion

The findings from FENopta data presented, underscore the promise of fenebrutinib in the treatment of RMS, demonstrating a reduction in MRI lesions alongside a favorable safety profile. Moreover, initial observations reveal significant penetration of the central nervous system, with detectable levels of fenebrutinib in cerebrospinal fluid (CSF) at concentrations clinically relevant for influencing the underlying mechanisms of chronic progressive disease biology in MS. This suggests that fenebrutinib may not only address acute relapses but also potentially modify the long-term progression of the disease.