Fenebrutinib Outperforms Teriflunomide on Relapse, MRI, and Biomarker Measures in Pooled FENhance Analysis
KEY TAKEAWAYS
- In 1,497 people with relapsing MS (RMS), fenebrutinib more than halved the annualized relapse rate compared with teriflunomide (0.06 vs 0.13).
- Fenebrutinib also reduced new MRI lesions, slowed brain volume loss, and lowered serum neurofilament light chain (NfL).
- Risk of 12-week composite confirmed disability progression was 16% lower with fenebrutinib. The 24-week result did not reach significance.
The Bruton tyrosine kinase (BTK) inhibitor fenebrutinib improved clinical, MRI, and biomarker outcomes compared with teriflunomide in a pooled analysis of the phase 3 FENhance 1 and 2 trials presented at MSToronto2026.
What is Fenebrutinib?
Fenebrutinib is an oral, CNS-penetrant, noncovalent, reversible, and highly selective BTK inhibitor. Each FENhance trial had previously shown superiority over teriflunomide on its primary end point, annualized relapse rate (ARR).
How Were the FENhance Trials Designed?
FENhance 1 and 2 were randomized, double-blind, double-dummy phase 3 studies. Adults aged 18 to 55 years with RMS and an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 were randomly assigned 1:1 to fenebrutinib 200 mg twice daily (n = 750) or teriflunomide 14 mg once daily (n = 747) for at least 96 weeks.
What Did the Pooled Analysis Show?
- Relapses: ARR was 0.06 with fenebrutinib vs 0.13 with teriflunomide (P < .001).
- MRI lesions: Gadolinium-enhancing T1 lesions per scan were 0.08 vs 0.32, and new or enlarging T2 lesions per year were 1.16 vs 5.64 (both P < .001).
- Brain volume: Annual total brain volume loss was reduced by 22.8% relative to teriflunomide (P < .001).
- Disability: Risk of composite confirmed disability progression was lower at 12 weeks (HR, 0.84; 95% CI, 0.71-0.99; P = .04) and numerically lower at 24 weeks (HR, 0.84; 95% CI, 0.68-1.02; P = .08).
- NfL: At week 48, mean serum NfL fell 22.3% with fenebrutinib vs 12.2% with teriflunomide (P < .001). In patients with baseline gadolinium-enhancing lesions, the reductions were 45.2% vs 28.4%.
What Does This Mean for Patients With Relapsing MS?
The investigators concluded that fenebrutinib had a consistent effect on relapse activity, disability progression, and markers of brain and neuroaxonal damage, supporting broad control of disease activity. Safety results were not included in this abstract.
Source
Giacomini PS, Boaventura M, Shi FD, et al. Efficacy of fenebrutinib versus teriflunomide in relapsing multiple sclerosis: pooled analysis results from the FENhance 1 and 2 studies. Abstract O089. Presented at: MSToronto 2026, the 10th Joint ACTRIMS-ECTRIMS Meeting; October 21-23, 2026; Toronto, Ontario, Canada.