I am going to be an optimist and give this new class of treatment a 75% chance of success (range 60-90%), mainly due to their anti-B-cell effects, and a 25% chance of failure. Why?
On a different topic, do you recommend that pwMS on Ocrevus who have had a decent response to the vaccine receive Evusheld? Do you have any concerns about risks (e.g., myocarditis) that may be significant but not yet identified because Evusheld has so far been given only to a small number of people (cf. the FDA’s information sheet on Evusheld). Neurologists in the US are starting to recommend Evusheld to their MS patients.
Just a question I am 61 yrs old am currently receiving Ocrevus infusions as you have said 65 yrs is the cut off age would I be able to register for the SIZOMOUS trials and if so how would I go about it
Reading today the UCL findings related to Asterzenica vaccine for COVID 19 , finding a link to Guiilian Barr , affects ??
From the early Polio vaccine 1956 to HepB as given a midwife 1987 ? and Flu vaccines given annually always knocked me back for several weeks , labeled MS , medically retired aged 46 , COVID Vaccine 2021 knocked me off for 6 weeks , as did COVID brought home with husband from hospital discharge March !
Your opinion on using Ixazomib and Ofatumumab TOGETHER? Won’t it be a really big hit depleting B cells and plasma cells? Treatment time 1-2 years let’s say?
I really wonder what the remaining T cells will do in this time period…
Seen some studies on bortezomib and Rituximab on lymphomas and their toxicity profile seemed acceptable, with Kesimpta and Ixazomib it should look even better
If BTK inhibitors prove effective it is likely to be 5 years before they are available. Are there any other treatments currently in trial which are seeking to address smouldering MS? Are these on the same timescale ie (the usual) “five years”?
Will BTK inhibitors be used as an IRT (short term blitz) or a maintenance therapy?
If a patient is on a DMT eg Natalizumab, can the BTK inhibitor (in 5 years time) just be added to their treatment regime, or will combination trials (DMT + BTK inhibitor) have to be undertaken to prove safety and efficacy?
Subject to these treatments coming to market in five years time, what, if anything, will prevent PwMS having access to them here in the UK and elsewhere?
Thank you for this post, great to read some positive news.
Re:
'Don’t forget ofatumumab and teriflunomide had the same effect on brain volume loss'
I'd previously understood that anti CD20s have no effect on BVL and teriflunamide has a small effect? Clearly I've got that wrong. On the graph shown it does indeed look like teri is a touche better than ofatumumab. Not sure how ofatumumab compares to no treatment?
Be that as it may, look forward to learning how BTKi phase III trials go. So, they are:
evobrutinib RRMS n=1860
masitinib naSPMS/PPS n=800
tolebrutinib RRMS n=1800
tolebrutinib naSPMS n=1290
tolebrutinib naPPMS n=900
As you say, comparison arm teriflunomide for RRMS. Placebo for na progressive MS.
Sounds like Merck (evobrutinib) playing it safe and cautiously, AB Science (masitinib) keeping it low key and focusing on progressive MS and Sanofi (tolebrutinib) hedging their bets and throwing everything at it!
I make that a total of 6650 trial places (3660 RRMS, 2990 naMS) surely some of them will be in UK? Particularly excited by na progressive MS trials.
Interesting subtle differences in eligibility criteria re EDSS and age.
I wonder how the progressive trials will deal with participants with signs of active MS? Record info and carry on? How many participants may want to leave? Hardly ethical to remain in trial with 50% chance of placebo.
How do you expect the BTKi class to compare with Anti-CD20 across (1) relapse suppression; (2) immune suppression? Will BTKi be a substitute for Anti-CD20 or a complement? Many on anti-CD20 are concerned about long-term immunosuppression especially in light of COVID being here to stay.
Not really clear to me which B cell subsets are inhibited and to which extend. Will it have an (big) effect on antibody production. The unclear effect it has on the innate part troubles me a bit. That said, i will take part in Perseus if I get through the screening and they will have me. Thanks for the letter
Thanks a lot for this comprehensive review on BTKinhibitors in MS. It's really exciting for MSologists and patients with MS. I have some questions on the topic:
1) In these several trials, did they study B cells subsets after treatments ? Did they study the impact on OCBs in CSF ?
2) Are BTK inhibitors only targettinng pathogenic B cells or even normal B cells?
3) Is the therapeutic response with BTKinhibitors slower compared to anti CD20 ? If yes, can BTKi be a maintenance therapy after induction with more rapidly active treatment for the disease?
4) How does the drug affect the IgG level and How to monitor this ? Is it same as other anti CD20 therapies ?
My 18yr old daughter, RRMS, dx 2019, current on ocralizumab, doing quite well despite daily subtle symptoms is intent on pursuing HSCT in the hope of halting disease progression. Should she wait for BTK inhibitors? Will that be a safer long term option or should she bite the HSCT bullet, have treatment sooner rather than later and take advantage of an early diagnosis before too much damage has accumulated?
Are there local (St.Louis MO USA) that would have this available for me to be a part of testing? I am 65 and the number of times I have inquired about being part of a test group, my Neuro has told I am too old. Thoughts?
Would an even greater chance of long term success or halting progress be a BTK + an ebv antivirals eg ATA188
Working in conjunction?
Based on a lot of estimates I'm hearing <5 years to market for the BTK. Would you think that's likely or too optimistic?
And is anyone doing a big comparative vs Tysabri / ocrevus / lemtrada etc?
Thank you, Prof. G.
On a different topic, do you recommend that pwMS on Ocrevus who have had a decent response to the vaccine receive Evusheld? Do you have any concerns about risks (e.g., myocarditis) that may be significant but not yet identified because Evusheld has so far been given only to a small number of people (cf. the FDA’s information sheet on Evusheld). Neurologists in the US are starting to recommend Evusheld to their MS patients.
Just a question I am 61 yrs old am currently receiving Ocrevus infusions as you have said 65 yrs is the cut off age would I be able to register for the SIZOMOUS trials and if so how would I go about it
Reading today the UCL findings related to Asterzenica vaccine for COVID 19 , finding a link to Guiilian Barr , affects ??
From the early Polio vaccine 1956 to HepB as given a midwife 1987 ? and Flu vaccines given annually always knocked me back for several weeks , labeled MS , medically retired aged 46 , COVID Vaccine 2021 knocked me off for 6 weeks , as did COVID brought home with husband from hospital discharge March !
Your opinion on using Ixazomib and Ofatumumab TOGETHER? Won’t it be a really big hit depleting B cells and plasma cells? Treatment time 1-2 years let’s say?
I really wonder what the remaining T cells will do in this time period…
Seen some studies on bortezomib and Rituximab on lymphomas and their toxicity profile seemed acceptable, with Kesimpta and Ixazomib it should look even better
Thanks for this post.
If BTK inhibitors prove effective it is likely to be 5 years before they are available. Are there any other treatments currently in trial which are seeking to address smouldering MS? Are these on the same timescale ie (the usual) “five years”?
Will BTK inhibitors be used as an IRT (short term blitz) or a maintenance therapy?
If a patient is on a DMT eg Natalizumab, can the BTK inhibitor (in 5 years time) just be added to their treatment regime, or will combination trials (DMT + BTK inhibitor) have to be undertaken to prove safety and efficacy?
Subject to these treatments coming to market in five years time, what, if anything, will prevent PwMS having access to them here in the UK and elsewhere?
Thank you for this post, great to read some positive news.
Re:
'Don’t forget ofatumumab and teriflunomide had the same effect on brain volume loss'
I'd previously understood that anti CD20s have no effect on BVL and teriflunamide has a small effect? Clearly I've got that wrong. On the graph shown it does indeed look like teri is a touche better than ofatumumab. Not sure how ofatumumab compares to no treatment?
Be that as it may, look forward to learning how BTKi phase III trials go. So, they are:
evobrutinib RRMS n=1860
masitinib naSPMS/PPS n=800
tolebrutinib RRMS n=1800
tolebrutinib naSPMS n=1290
tolebrutinib naPPMS n=900
As you say, comparison arm teriflunomide for RRMS. Placebo for na progressive MS.
Sounds like Merck (evobrutinib) playing it safe and cautiously, AB Science (masitinib) keeping it low key and focusing on progressive MS and Sanofi (tolebrutinib) hedging their bets and throwing everything at it!
I make that a total of 6650 trial places (3660 RRMS, 2990 naMS) surely some of them will be in UK? Particularly excited by na progressive MS trials.
Interesting subtle differences in eligibility criteria re EDSS and age.
I wonder how the progressive trials will deal with participants with signs of active MS? Record info and carry on? How many participants may want to leave? Hardly ethical to remain in trial with 50% chance of placebo.
How do you expect the BTKi class to compare with Anti-CD20 across (1) relapse suppression; (2) immune suppression? Will BTKi be a substitute for Anti-CD20 or a complement? Many on anti-CD20 are concerned about long-term immunosuppression especially in light of COVID being here to stay.
Not really clear to me which B cell subsets are inhibited and to which extend. Will it have an (big) effect on antibody production. The unclear effect it has on the innate part troubles me a bit. That said, i will take part in Perseus if I get through the screening and they will have me. Thanks for the letter
Thanks a lot for this comprehensive review on BTKinhibitors in MS. It's really exciting for MSologists and patients with MS. I have some questions on the topic:
1) In these several trials, did they study B cells subsets after treatments ? Did they study the impact on OCBs in CSF ?
2) Are BTK inhibitors only targettinng pathogenic B cells or even normal B cells?
3) Is the therapeutic response with BTKinhibitors slower compared to anti CD20 ? If yes, can BTKi be a maintenance therapy after induction with more rapidly active treatment for the disease?
4) How does the drug affect the IgG level and How to monitor this ? Is it same as other anti CD20 therapies ?
Thanks :)
What's the upper age ;limit for SIZOMOUS?
My 18yr old daughter, RRMS, dx 2019, current on ocralizumab, doing quite well despite daily subtle symptoms is intent on pursuing HSCT in the hope of halting disease progression. Should she wait for BTK inhibitors? Will that be a safer long term option or should she bite the HSCT bullet, have treatment sooner rather than later and take advantage of an early diagnosis before too much damage has accumulated?
Are there local (St.Louis MO USA) that would have this available for me to be a part of testing? I am 65 and the number of times I have inquired about being part of a test group, my Neuro has told I am too old. Thoughts?
Barb K