MS News The Hare and Tortoise Race for BTK inhibitors. A pit stop created by the regulators


These are done to stop a crash.

Brutons tyrosine kinase inhibitors (BTKi) are the next bid hope for pharma and they all after the same goal to develop their drug development programmes and to start selling drug. This drug blocks signalling of B cells and macrophages and so is an essentially no brainer for relapsing MS, as every drug that works in MS blocks B cells, but targeting microgla is a big hope for progressive MS. So companies are doing trials in relapsing and progressive MS.

As mentioned the relapsing MS should be a no-brainer as phase II studies have already showed that it works to inhibit relapses. Personally I would like to see head to head with CD20-depleter as I have a feeling the BTKi may not be as potent, but let’s see. As for progressive MS we live in hope. We all think that microglia are involved in MS but they can be good and bad guys and so we have to wait and see what happens as it is the balance of good verses bad that determines success.

In the race of approval are a number of companies there first to report was on evobrutinib and is in two trials for relapsing MS (n=930 each. Reported (clinical Finish 2023), but there are many , many others including in the hunt: tolebrutinib (n=900 each oftwo trials Reported (clinical Finish 2023) and in primary progressive (n=990. Finish 2024) and secondary progressive MS (n=1290. Finish 2024). Then there is fenebrutinib in relapsing MS n=760. Finish 2025) and primary progressive MS against placebo and ocrelizumab (n=946. Reported finish 2025) and remibrutinib for relapsing MS (n=800 in two traisl reported finish 2025) and then there are others like orelabrutinib (n=160), but there are more in development for MS and other autoimmune conditions

Check out for alternative dates and trial numbers


Who will get their first?, who will be the best?, importantly who will be the safest?. Phase I looks for mainly safety, Phase II looks for safety and a hint of efficacy, but phase III is for efficacy and safety and phase IV after approval is to look for safety. In phase II few people get the drug in phase IV it is thousands and so the rare side effects pop up. Tolebrutinib is being assessed in alot of people in MS and is in a late stage trial in Myasthenia Gravis (Autoimmune disease of the nerve muscle junction) and earlier studies for kidney and liver problems.

So you may be interested to know that the trails of have been put on hold by the FDA whilst they ascertain if there are issues due to reversible, drug-induced liver injury. 

Participants in the U.S. who have been in the trial for fewer than 60 days shall suspend study drug, importantly, U.S. participants who have completed at least 60-days in the trial should continue treatment. If you are on the study don’t panic but wait to be contacted by your neuro.

We should not panic yet. This does not mean the programme and the hope atttached to it are shot down in flames as we have been here before, e.g. natalizumab and alemtuzumab where development was suspended whilst a strategy for reducing risk was developed. However, it re-inforces the gratitude that we should have for people undertaking the trials and highlights the perils of drug development, so when we moan about drug prices we have to remember that the costs of success and failure have to be recouped.

CoI: Multiple but none are considered to be relevant but multiple

Disclaimer. This is the views of the author and no-one else

Perseus killed the medusa that turned people into stone, hercules ws a strong guy and Gemini represents the twins Castor and Pollux but it was also a

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  • I did see mast cells in that chart

    (maybe its me 🙂 )

    Are bkt present in mast cells also?


  • Thank you for the update MD1. This is a more detailed explanation than any other “updates” I have received on this announcement thus far.

    Let’s hope the pause is for the best and they can resume shortly, but I am generally skeptical of BTKi until I see the data. Every neuro I have seen touts BTKi as “the next best drug”, which is probably what they said about anti-CD20s or NAT or drug x.

    One question, how do I perform a search on biogps? I was interested in looking up CLAD.

    By the way, this is one of the best lines of yours so far this year (IMO)……”as every drug that works in MS blocks B cells” 😂😂 burn!

    • BioGPS is a gene expression site, not drugs
      (a) Go to Biogps
      (b) in the search gene box add gene e.g. BTK press enter
      Confirm gene and the species and click on the geen of interest in the table e.g. No. 1 Bruton tyrpsoine kinase.
      Press Change data set press on default datasets (5)
      Select Primary Cell atlas (745 samples)
      or GeneAtlas U133A, gcrma (176 samples)
      I wouldnt bother with the barcode on normal tissue
      If you want the data press downloads

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