First of all, I would like to wish all readers of MS-DocBlog a happy and successful new year. – Stay healthy and hopeful, despite all adversities.
Speaking of adversities – this brings us right back to the topic: There is news about the BTKi. Shortly before Christmas 2025, more precisely on 15.12.2025, Sanofi, the manufacturer of the BTKi Tolebrutinib, published a press release announcing that the so-called PERSEUS study had missed its primary endpoint (amsel.de had already reported). This was anything but good news.
Disappointing news shortly before the end of the year
What exactly is it about? PERSEUS is the global phase III study that investigated the effectiveness and safety of Tolebrutinib compared to placebo in patients with primary progressive multiple sclerosis (PPMS). It is the fourth and final study in the extensive study program on the effect of Tolebrutinib in different forms of MS, alongside GEMINI I + II (Tolebrutinib in relapsing MS – RMS) and HERCULES (Tolebrutinib in non-relapsing secondary chronic progressive MS – nrSPMS).
In the PERSEUS study, participants received either a daily oral dose of Tolebrutinib or a corresponding placebo for a period of up to approximately 60 months. Inclusion criteria were an age between 18 and 55 years, diagnosis of PPMS according to the revised McDonald criteria from 2017, and an EDSS score between 2.0 and 6.5. The primary endpoint was confirmed disability progression after six months (cCDP). This primary endpoint was not achieved, i.e. the disability progression of the PPMS patients could not be significantly delayed compared to placebo. The study did not reveal any new aspects regarding drug safety.
This result is all the more disappointing because the positive results of the HERCULES study were previously enthusiastically received. – Finally, there was an interesting therapy perspective for the treatment of chronic MS courses, after HERCULES showed that it could significantly reduce the disability progression of patients with nrSPMS compared to placebo. Given the current assumption of similar immunopathological mechanisms in PPMS and nrSPMS, the result of the PERSEUS study is therefore not so easy to classify.
A few days later came the news that the US Food and Drug Administration FDA has initially rejected the approval of Tolebrutinib for non-relapsing secondary progressive multiple sclerosis (SPMS). – They will coordinate with the manufacturer on further procedures (amsel.de had already reported on this in an annual overview: Therapy of MS 2025 and recent developments).
BTKi: Approval in Europe still open
In Europe too, the approval of Tolebrutinib by the European Medicines Agency EMA is pending; a decision is expected in the coming months and it remains to be seen how the Europeans will handle this situation.
Overall, the BTKi topic is characterized by quite a bit of “ups and downs”. It was not long ago that the company Roche communicated positive study results for their BTKi Fenebrutinib both in relapsing and in PPMS. These results are – I had already commented on this on DocBlog – actually a signal that the concept of BTKi makes sense and has potential. The current situation now at least questions the potential of Tolebrutinib, although the exact study results should be awaited first – so far only a press release has been published, which does not allow an exact classification of the study data.
This would probably also be my recommendation – wait for further development, which is of course not satisfactory news for those affected by progressive MS who are currently waiting for the approval of Tolebrutinib. However, I personally believe – even if the PERSEUS study has turned out negative – that BTK inhibitors have future potential and that it would also be desirable to transfer the positive results of the HERCULES study into reality. Therefore, I hope for plausible explanations after reviewing the complete study results and ultimately for the early approval of the first BTKi.
AMSEL and MS-Docblog will inform you as soon as there is news about BTKi.
This post was translated from German to English with the help of AI.
