- Phase III FENhance 1/2 (n=1,497) randomized 1:1 for ≥96 weeks showed fenebrutinib reduced ARR versus teriflunomide by 51.1% and 58.5% in FENhance 1 and 2 respectively.
- Fenebrutinib reduced MRI activity: T1‑Gd+ lesions down 70.7%/77.6% and new/enlarging T2 lesions down 76.0%/82.5% versus teriflunomide.
- Safety signals: liver enzyme elevations >3×ULN were comparable (~5.6–7.3%), infections similar, but deaths were imbalanced (7 deaths, 0.9% fenebrutinib vs 1 death, 0.1% teriflunomide during reporting period).
- FENtrepid in PPMS met non‑inferiority versus ocrelizumab, and Roche plans regulatory submission of the combined RMS and PPMS Phase III data.
Key results
Phase III FENhance 1 and 2 (total n=1,497) randomized 1:1 for ≥96 weeks showed fenebrutinib reduced annualised relapse rate versus teriflunomide by 51.1% and 58.5%, equating to roughly one relapse every 17 years compared with teriflunomide.
MRI and disability
Fenebrutinib markedly reduced MRI inflammation: T1‑Gd+ lesions down 70.7%/77.6% and new/enlarging T2 lesions down 76.0%/82.5% (FENhance 1/2); 12‑week composite confirmed disability progression showed numerical risk reductions (HR 0.80 and 0.87), and a post‑hoc EDSS+9HPT composite gave HR 0.74 (26% risk reduction) in FENhance 1.
Safety
Liver enzyme elevations >3×ULN were comparable (~5.6–7.3%); one Hy’s Law case occurred in each arm (both resolved after drug discontinuation); infection rates were similar; serious AEs were 8.6% vs 8.9% (FENhance 1) and 11.2% vs 6.1% (FENhance 2); deaths were imbalanced during the reporting period (seven deaths, 0.9%, in the fenebrutinib arm vs one death, 0.1%, in the teriflunomide arm), with varied causes.
Mechanism, PPMS and next steps
Fenebrutinib is a CNS‑penetrant, reversible non‑covalent BTK inhibitor selective for BTK (~130×), designed to target B cells and microglia; the PPMS FENtrepid study met non‑inferiority versus ocrelizumab, and Roche will submit the totality of RMS and PPMS Phase III data to regulators.
