Roche’s fenebrutinib halves RMS relapse rate to ~1 per 17 years

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.