At the end of April, the annual meeting of the American Academy of Neurology (AAN) took place in Chicago. I had the opportunity to attend the congress on site and therefore want to summarize some news for my readers. The focus here is primarily on news from the AAN 2026 on BTKi.
It should be noted that the AAN covers all areas of neurology and also addresses many professional political issues of American colleagues. Therefore, multiple sclerosis is just one of many topics. In addition, current developments in the field of Alzheimer’s research and advances in the treatment of genetic diseases – at least in my perception – are more in focus than developments in neuroimmunology and MS research. Although there were certainly some highlights here.
Fenebrutinib study with dummy
At the AAN in Chicago, the results of the FENhance 1 and 2 studies on the effect of the BTKi Fenebrutinib in relapsing MS were presented (for classification see also DocBlog post “Systematic overview of current BTKi study programs“). FENhance 1 and 2 are two identical studies in which the effects of Fenebrutinib and Teriflunomide were compared in over 740 MS patients each. More precisely, it is a so-called double-blind, double-dummy design. This means that the Fenebrutinib group received Fenebrutinib 200 mg, twice a day as a tablet, and additionally a Teriflunomide placebo and the Teriflunomide group received a daily Teriflunomide tablet with 14 mg and two Fenebrutinib placebos). Safety data were also collected in both studies.
The primary endpoint of the study was the annual relapse rate, important secondary endpoints were the delay in disability progression and new lesions in MRI. The demographic data of the study patients is interesting – it is noticeable that rather young and shortly ill MS patients were included in the study. The average time since diagnosis was only 1 year, less than 20% of the subjects had prior therapy and the average EDSS was rather low at 2.5 points.
In this rather early MS cohort, the administration of Fenebrutinib led to a 51% (FENhance 1) or 58% (FENhance 2) relative reduction in the annual relapse rate – a highly significant difference compared to the established MS drug Teriflunomide (= Aubagio). Also with regard to the reduction of contrast-enhancing lesions and new T2 lesions in MRI, Fenebrutinib showed a clear superiority. The effect was visible in all subgroups, but younger patients with low EDSS and evidence of acute inflammation in MRI benefited particularly. As for the delay in disability progression, a weakly significant superiority over Teriflunomide was observed in the pooled analysis of both studies.
Smoldering MS, relapsing MS
This result is quite surprising. In all other studies with Bruton tyrosine kinase inhibitors in relapsing MS, the previously used BTKi (Evobrutinib and Tolebrutinib) showed no statistical difference compared to Teriflunomide in terms of the effect on the annual relapse rate. Therefore, the question arose in the past whether BTKi can be used with a clear conscience as long as focal inflammation (relapses / MRI activity) plays a dominant role (usually early in the course of the disease). This would no longer be the question for Fenebrutinib in view of the study results. On the other hand, BTKi are attractive mainly because they are believed to have considerable potential in preventing smoldering inflammation that leads to disease progression.
This assumption was also confirmed by the successful study on Tolebrutinib in SPMS. Now, however, the prevention of progression in the FENhance studies is at a level that raises the question of whether this was primarily due to the strong anti-inflammatory effect of Fenebrutinib. A separation of the effect on relapses here and on disease progression there (medical “dissociation”), as within the Tolebrutinib study program, can only be derived from the Fenebrutinib study program to a limited extent.
Safety profile of Fenebrutinib
The safety profile of Fenebrutinib was particularly interested in liver values. However, the increases in liver values were comparable in the Teriflunomide group and the Fenebrutinib group, which is reassuring. What still needs to be clarified is the imbalance between the deaths in the Fenebrutinib group and the Teriflunomide group, even though the vast majority of causes of death were not seen in connection with Fenebrutinib by the study doctors. The manufacturer will certainly take a more detailed position on this.
At this point it should now be mentioned that a few days ago (right after the AAN meeting) the Drug Subcommittee of the European Medicines Agency gave a positive recommendation for the approval of the BTKi Tolebrutinib – amsel.de reports in detail on the EMA recommendation for Tolebrutinib. The active ingredient, which will be available under the trade name Cenrifki® in the future, is (subject to the final decision of the European Commission) to be approved for the treatment of patients with secondary chronic progressive MS who have not had relapses in the last 2 years. This is certainly very good news for many patients with SPMS.
This post was translated from German to English with the help of AI.
