FENtrepid

Fenebrutinib

FENtrepid reported that investigational oral fenebrutinib was non-inferior to ocrelizumab for composite disability progression in primary progressive multiple sclerosis.

Phase
Phase III
Population
Primary progressive multiple sclerosis (PPMS)
Controlled period
Oct 26, 2020 — Sep 17, 2025

What was compared

Randomized 1:1Double-blindDouble-dummyActive-controlled
Intervention

Fenebrutinib

200 mg orally twice daily with ocrelizumab-matching placebo

Comparator

Ocrelizumab

Intravenous treatment with fenebrutinib-matching placebo

985 randomizedAt least 120 weeks controlled phase

Primary endpoint

Prespecified outcome

Time to 12-week composite confirmed disability progression

Minimum 120 weeks

Outcome figure

Primary endpoint results

Intervention Comparator or reference

12-week composite confirmed disability progression

Hazard ratio (95% CI)

Minimum 120 weeks
Fenebrutinib vs ocrelizumab0.88 (0.75–1.03)

Fenebrutinib met the prespecified non-inferiority endpoint (HR 0.88; 95% CI 0.75–1.03); this was not a superiority finding.

Selected secondary outcomes

Upper-limb worsening

Risk of confirmed worsening on the nine-hole peg test was 26% lower with fenebrutinib (HR 0.74; 95% CI 0.56–0.98).

Post-hoc two-component composite

A post-hoc EDSS-plus-nine-hole-peg composite favored fenebrutinib (HR 0.78; 95% CI 0.64–0.95).

Who was studied

Key inclusion criteria

  • Age 18–65 years
  • PPMS diagnosis based on McDonald criteria 2017
  • Documented disability progression during the preceding 12 months
  • Baseline EDSS 3.0–6.5 with pyramidal functional-system score at least 2

Key exclusion criteria

  • Active infection, immunodeficiency, or specified prior potent immunosuppression
  • Acute or unstable chronic liver disease
  • Clinically important comorbidity that could confound efficacy or safety assessment

Participants at baseline

CharacteristicFenebrutinibN=493OcrelizumabN=492
Age, years — mean ± SD49.0 ± 10.348.9 ± 10.2
Female sex — %50.1%49.0%
Time since MS symptom onset, years — mean ± SD9.2 ± 6.98.8 ± 6.5
Time since PPMS diagnosis, years — mean ± SD4.8 ± 5.44.7 ± 5.4
EDSS — median (range)5.0 (2.5–6.5)5.0 (1.5–6.5)
Prior DMT use — %22.3%24.8%
Gadolinium-enhancing T1 lesions present — %10.3%11.2%

SD: standard deviation; EDSS: Expanded Disability Status Scale; DMT: disease-modifying therapy.

Source: Roche, ACTRIMS 2026 presentation, Slide 22

Safety signal

  • Transient, reversible liver-enzyme elevations were more frequent with fenebrutinib than ocrelizumab: 13.3% versus 2.9%.
  • Serious adverse events occurred in 19.1% and 18.9%, respectively.
  • Fatal events occurred in 1.4% with fenebrutinib and 0.2% with ocrelizumab; investigators assessed them as unrelated and reported no pattern.

Why it mattered

FENtrepid reported non-inferiority of oral fenebrutinib to ocrelizumab on composite disability progression in PPMS. It tested a possible oral alternative against the established active treatment; non-inferiority does not demonstrate superiority, and fenebrutinib remains investigational.

Important limitation

Non-inferiority does not establish superiority, and the supportive two-component analysis was post hoc. Fenebrutinib remains investigational, and no peer-reviewed primary Phase III paper was verified.

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