At this year’s ECTRIMS Meeting in Copenhagen, the data from the study program of the Bruton-Tyrosine-Kinase (BTK) inhibitor Tolebrutinib was presented. And what can I say – fortunately there were positive news this time.
Last year, just before Christmas, we received the message from Merck that the study program with the BTK inhibitor Evobrutinib did not achieve its primary endpoint. This was quite a disappointment because a lot was expected from the concept of inhibiting Bruton-Tyrosine Kinase (BTK) – especially with regard to slowing down progression in MS. But Evobrutinib was not superior to the comparator substance Teriflunomide (Aubagio®) in preventing relapses or disease progression.
Study results for Tolebrutinib at ECTRIMS
Therefore, the presentation of the data on Tolebrutinib was eagerly awaited. Tolebrutinib, the active substance of Sanofi, was tested in an extensive study program. In two studies (GEMINI 1 and 2), Tolebrutinib (like Evobrutinib) was compared with the established MS drug Teriflunomide (Aubagio®). In addition, the substance was tested against placebo in the so-called HERCULES study in non-active secondary progressive MS (non-relapsing SPMS, nrSPMS). The results of these three studies were presented at ECTRIMS. The results of another study (PERSEUS) in primary progressive MS (PPMS) are not yet available and will probably be reported in spring 2025.
In relapsing-remitting MS, no difference could be found between the new substance Tolebrutinib and the established substance Teriflunomide in relation to the primary endpoint “annual relapse rate”. Although the relapse rate was very low in both groups, it was not different. However, a significant superiority of Tolebrutinib in preventing disability progression was shown in the GEMINI studies. This finding is important – although only a secondary study endpoint – because Tolebrutinib significantly prevented disease progression (primary study endpoint in this study) compared to placebo in the HERCULES study.
Positive results in preventing disease progression
In the HERCULES study, as already mentioned above, patients with long-standing MS (> 17 years) were included, who had not had clinical relapses for more than 7 years and showed contrast-enhancing lesions in a very small percentage (12%). In this group, which is difficult to treat from a clinical point of view, the progression of disability could be significantly delayed by the administration of Tolebrutinib.
On the basis of both studies, it can therefore be assumed that the BTKi Tolebrutinib, although it does not mediate an extraordinarily strong anti-inflammatory effect, is nevertheless able to significantly influence disease progression – and this is one of the greatest challenges of current MS therapy.
Accordingly, this result is scientifically pleasing. Because it opens up new perspectives with regard to preventing disease progression and will drive developments in this area. It remains to be seen to what extent patients will benefit from these study results and which patient groups will benefit. It is not yet known how the European approval authority will evaluate the results and for whom the new substance will be approved.
It should also be mentioned that treatment with Tolebrutinib is not entirely straightforward. Although Tolebrutinib was well tolerated, there were – albeit very rare – liver function disorders, which is why the substance will only be used under extensive monitoring of liver values.
This post was translated from German to English with the help of AI.
