Roche is eyeing regulatory approval for its oral multiple sclerosis (MS) hopeful, fenebrutinib, after the drug met its primary endpoints in two Phase III trials.
During the FENhance 2 (NCT04586023) study, the Bruton’s tyrosine kinase (BTK) inhibitor significantly reduced annualised relapse rates compared with Sanofi’s commonly prescribed therapy, Aubagio (teriflunomide). This effect was seen over a 96-week treatment period in patients with relapsing MS (RMS).
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On top of its activity in RMS, fenebrutinib has proven to be non-inferior to Genentech’s (a Roche subsidiary) MS market best-seller, Ocrevus (ocrelizumab) in the pivotal FENtrepid study (NCT04544449) in primary progressive MS (PPMS). Currently, Ocrevus is the only disease-modifying therapy approved for PPMS.
This was confirmed by the delay in the onset of composite confirmed disability progression after 120 weeks of treatment. The drug also exhibited a numerical benefit over Ocrevus by week 24 – an effect that was sustained throughout the observation period.
These Phase III wins follow the positive results of the open-label extension portion of the Phase II FENopta trial (NCT05119569), which determined that fenebrutinib can trigger a near-complete suppression of disease activity over the 96-week period.
Alongside these trials, Roche is also conducting the FENhance (NCT04586010) study in RMS, which is set to read out in H1 2026. Once the data from this study is collated, the Swiss pharma will consider regulatory submission for fenebrutinib.
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By GlobalDataIn both the FENtrepid and FENhance 2 trials, fenebrutinib’s safety profile was consistent with previous studies. However, the drug was previously placed on a clinical hold by the FDA after it triggered liver enzyme elevations in two patients during the FENhance study.
According to Roche, the results of these late-stage trials could see fenebrutinib become the first BTK inhibitor to gain approval in both PPMS and RMS, which could line it up to become a “best-in-disease oral treatment”, noted Roche’s CMO and head of global product development, Levi Garraway.
BTK inhibitors turn heads in MS
Fenebrutinib’s performance in its respective Phase III trials will be welcome news for Roche, which is looking to cement its position in the MS treatment paradigm.
The company currently holds a notable share of the market, having struck gold with the approval of Ocrevus in 2017. However, the therapy is moving ever closer to the patent cliff, with its US patent set to expire in 2029.
Analysts at GlobalData forecast that this will cause a 66% dip in sales for Ocrevus, dropping from a peak of $7bn in 2027 to $2.3bn in 2034.
If approved, fenebrutinib could offer respite from the steep drop-off in Ocrevus sales, as analysts at GlobalData forecast the drug will reach blockbuster status by 2031, with sales due to reach $1.31bn.
However, the Swiss pharma is not the only company looking to commercialise an oral BTK inhibitor in MS, as Sanofi has already submitted a biologics licence application (BLA) to the US Food and Drug Administration (FDA) for tolebrutinib.
If approved, tolebrutinib could offer significant competition to fenebrutinib, as it has a slight, once-daily dosing edge over fenebrutinib, which is administered twice-daily.
Thus far, tolebrutinib’s route to market has been far from simple, with Sanofi facing efficacy, safety and regulatory roadblocks throughout the process. Most recently, the FDA delayed its approval decision for the drug in non-relapsing secondary progressive MS (nrSPMS).
If approved, GlobalData predicts tolebrutinib to reach blockbuster status earlier in 2030, with sales expected to reach $1.41bn in 2031.
Another contender in the race to commercialise a BTK inhibitor is Roche’s compatriot, Novartis, which is looking to get Rhapsido (remibrutinib) to market in the RMS population. The drug was most recently approved in chronic spontaneous urticaria, getting FDA approval in September 2025.
In conversation with Clinical Trials Arena, three MS experts touted the future potential of BTK inhibitors in the MS market, noting that their efficacy in hard-to-treat subsets and capacity to target both central and peripheral inflammation could earn them a place in the treatment paradigm.
