FENhance 1 & 2
Fenebrutinib
The parallel FENhance trials reported that investigational fenebrutinib reduced relapses and MRI lesion activity more than teriflunomide in relapsing multiple sclerosis.
- Phase
- Phase III
- Population
- Relapsing multiple sclerosis (RMS)
- Controlled period
- Mar 17, 2021 — Jan 27, 2026
What was compared
Fenebrutinib
200 mg orally twice daily with matching placebo
Teriflunomide
14 mg orally once daily with matching placebo
Primary endpoint
Annualized relapse rate
Minimum 96 weeks in each trial
Primary endpoint results
FENhance 1 — annualized relapse rate
Adjusted relapses per participant-year
FENhance 2 — annualized relapse rate
Adjusted relapses per participant-year
Fenebrutinib reduced adjusted relapse rates by 51.1% in FENhance 1 (rate ratio 0.49; 95% CI 0.33–0.73; P<0.001) and 58.5% in FENhance 2 (0.42; 95% CI 0.28–0.61; P<0.00001).
Selected secondary outcomes
New T1 gadolinium-enhancing lesions and new or enlarging T2 lesions were significantly reduced in both trials.
Numerical reductions favored fenebrutinib but the confidence intervals included no difference in both trials.
Who was studied
Key inclusion criteria
- Age 18–55 years
- RMS diagnosis based on McDonald criteria 2017
- Baseline EDSS 0–5.5
- Able to complete protocol-defined walking and upper-limb assessments
Key exclusion criteria
- Primary progressive MS or non-active secondary progressive MS
- Active infection or clinically important immune, hepatic, or systemic disease
- Disease duration over 10 years with baseline EDSS below 2.0
Participants at baseline
FENhance 1
| Characteristic | FenebrutinibN=374 | TeriflunomideN=372 |
|---|---|---|
| Age, years — mean ± SD | 36.1 ± 9.4 | 35.8 ± 9.5 |
| Female sex — n (%) | 232 (62.0%) | 253 (68.0%) |
| Time since symptom onset, years — median (range) | 3.8 (0.2–29.2) | 3.4 (0.1–33.2) |
| Time since RMS diagnosis, years — median (range) | 1.1 (0.1–29.2) | 1.2 (0.1–33.2) |
| EDSS — median (range) | 2.5 (0.0–6.0) | 2.5 (0.0–5.5) |
| Prior DMT use — n (%) | 56 (15.0%) | 61 (16.4%) |
| Gadolinium-enhancing T1 lesions present — n (%) | 126 (33.7%) | 126 (33.9%) |
SD: standard deviation; EDSS: Expanded Disability Status Scale; DMT: disease-modifying therapy.
Source: Roche, AAN 2026 presentation, Slide 16
FENhance 2
| Characteristic | FenebrutinibN=376 | TeriflunomideN=375 |
|---|---|---|
| Age, years — mean ± SD | 36.4 ± 9.4 | 34.8 ± 9.2 |
| Female sex — n (%) | 264 (70.2%) | 246 (65.6%) |
| Time since symptom onset, years — median (range) | 3.9 (0.1–36.4) | 2.6 (0.1–30.8) |
| Time since RMS diagnosis, years — median (range) | 1.0 (0.0–28.2) | 0.6 (0.0–26.5) |
| EDSS — median (range) | 2.5 (0.0–6.0) | 2.0 (0.0–6.0) |
| Prior DMT use — n (%) | 80 (21.3%) | 73 (19.5%) |
| Gadolinium-enhancing T1 lesions present — n (%) | 119 (31.6%) | 116 (30.9%) |
SD: standard deviation; EDSS: Expanded Disability Status Scale; DMT: disease-modifying therapy.
Source: Roche, AAN 2026 presentation, Slide 16
Safety signal
- Liver-enzyme elevations above three times the upper limit of normal were similar between treatment groups in both trials.
- In FENhance 1, the sponsor reported one case meeting Hy’s Law criteria in each treatment group—a liver-test pattern signaling potential serious drug-induced liver injury. Both participants had no reported symptoms, and the abnormalities resolved after treatment discontinuation.
- Across the two reporting periods, seven deaths occurred with fenebrutinib and one with teriflunomide; causes and timing varied, and an additional fenebrutinib-arm death occurred later.
Why it mattered
FENhance 1 and 2 reported replicated Phase III relapse and MRI advantages for fenebrutinib over an active oral comparator. The results support the investigational BTK-inhibitor strategy in RMS, but congress and sponsor reporting does not replace a peer-reviewed paper or regulatory assessment.
Important limitation
Fenebrutinib remains investigational in MS. The current efficacy evidence comes from a conference presentation and sponsor report rather than a peer-reviewed primary paper, and the fatal-event imbalance requires careful regulatory and clinical interpretation.