On November 10, 2025, Roche released a press release announcing that Fenebrutinib has reached its primary endpoint in the first Phase III trial (FENhance 2) of two similarly designed pivotal Phase III trials (FENhance 1 and 2) in patients with relapsing multiple sclerosis (RMS). The study was able to show that Fenebrutinib – a Bruton’s tyrosine kinase (BTK) inhibitor currently under development – significantly reduces the annual relapse rate over a period of 2 years compared to Teriflunomide (Aubagio®). In addition, Roche announced that Fenebrutinib was also able to slow the progression of disability in the pivotal PPMS study (FENtrepid), similar to Ocrelizumab, the only approved therapy for PPMS, which served as a comparator in this study.
Even though no further details of the studies are known yet, these are initially very good news: Fenebrutinib, like Tolebrutinib – for which positive results for the treatment of progressive MS were recently published – is an oral Bruton’s tyrosine kinase inhibitor (BTKi). BTKi can penetrate the central nervous system (CNS) as “small molecules” and have an effect on both B cells and microglia cells – two cell types that are important for disease progression. However, unlike Tolebrutinib, Fenebrutinib binds non-covalently, so it does not form an irreversible bond with its target structure.
RMS and PPMS Studies
Similar to Tolebrutinib’s approval program, Fenebrutinib’s Phase III program includes two studies (FENhance 1 and 2) for relapsing MS (RMS). Here, Fenebrutinib was compared to the active comparator Teriflunomide, an established, moderately effective drug for the treatment of relapsing MS. A total of almost 1,500 patients were included in FENhance 1 and 2 and were randomized in equal ratios to either Fenebrutinib (2 tablets daily) or Teriflunomide. The primary endpoint was the annual relapse rate. In addition, the study program included a study for primary progressive multiple sclerosis (PPMS – FENtrepid). This study is of great interest because Fenebrutinib was not compared to placebo (as often in studies on progressive MS), but to Ocrelizumab – the only drug so far approved for the treatment of PPMS and also one of the most effective substances for the treatment of RMS. A total of 985 patients were included in this study, who were randomized in equal proportions to either oral Fenebrutinib or intravenous Ocrelizumab.
Of course, more data is needed to classify the study results. These will be communicated in the first half of 2026. Only then will it be possible to evaluate the effectiveness and safety of Fenebrutinib – also in comparison to other MS therapies – any current attempts at interpretation would be speculative.
However, it can already be stated at this point that the hopes placed in the development of BTKi were not unfounded. Ultimately, the results of the Fenebrutinib studies confirm the potential of the substance group with regard to an effect on key drivers of disease progression in MS. This will also increase confidence in the effect of Tolebrutinib, which will be the first BTKi to receive approval in the spring of next year and will then be available for the treatment of MS patients.
The more detailed results of the Fenebrutinib studies expected shortly will then help to more precisely define the areas of application of this new group of substances and thus achieve the best value for MS patients. So the anticipation continues.
This post was translated from German to English with the help of AI.
