The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
Discuss the article on the Forums.

Ocrelizumab?

Discussion in 'Rituximab: News and Research' started by jaybee00, Feb 13, 2016.

  1. jaybee00

    jaybee00

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    Hello,

    Is there any reson to expect that ocrelizumab would be more effective (or have fewer side effects) than rituximab for CFS? They both do the same thing by the same mechanism, correct?

    Thanks
     
  2. BurnA

    BurnA Senior Member

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    Marky90 likes this.
  3. jaybee00

    jaybee00

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    Thanks, my bad. So to summarize....

    Ocrelizumab is humanized, and rituximab is not, but this might not make any difference; ocrelizumab may be slightly more potent in depleting B cells.
     
  4. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    I think that`s the gist of it Jaybee00, maybe @Jonathan Edwards knows if there`s anything more.
     
  5. BurnA

    BurnA Senior Member

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    I'm pretty sure Dr Edwards said he doesn't see ocrelizumab in the future of ME/CFS and that there are better b cell depleting agents in the pipeline.
     
  6. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Yeah true, but which agents? I see few reasons not to do a trial, if there are no other obvious choices about.
    Supposedly we need agents who reach lymph nodes, bone marrow?, spleen.
    Why does rtx not work here very well? I have no ida, but iv`e read that to be the case, and i lack understanding of why.
     
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  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Ocrelizumab was mark 2, even the same company is on about mark 4 or mark 5 now. There is one particular antibody in development that has a more powerful B cell killing effector mechanism. I suspect they are all humanised (or human) now. Which would be the next one to be tried out will be a matter of practicalities and politics.
     
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  8. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Thanks prof:)

    Interesting insight!

    I guess it makes sense to wait until the phase 3-trials are done before another b-cell depletion study is carried out. Another one than rtx, that is
     
  9. BurnA

    BurnA Senior Member

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    I'm assuming the new ones being referred to are not on the market yet and maybe not even in phase 3 trials - would that be correct ?
    If so it could be many years yet before an ME trial with these drugs.

    I'd like to know the rationale or politics behind releasing a new drug. Do they wait until a sufficient improvement over an existing drug is achieved, but even at that there is no incentive for the patent owner to release a new drug. They would just be taking market share from themselves, although they may be able to extend patent lifetime.
     
    Marky90 likes this.
  10. deleder2k

    deleder2k Senior Member

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  11. Wonkmonk

    Wonkmonk Senior Member

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    Germany
    I know it's an old thread, but if I may ask: Why is it important how potent the MAB is, given that Rituximab at doses used in the Norwegian trials usually destroys all B cells and they are 0 in the blood after just a few days?

    Couldn't a more potent antibody just destroy them a few days faster? Given the timeframe for response to treatment (2-6 months minimum), this shouldn't matter much, right?
     
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  12. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    B cells in the blood are not the only ones and probably not the important ones. They may be 1% of the total. Most B cells are in lymph nodes and spleen where they hide in clusters protected by nurse cells carrying complement inhibitors. That makes them harder to kill. We do not know how many B cells in lymph nodes are killed by any of these drugs but it is almost certainly not all, at least in many cases. So there is room for more powerful versions.
     
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  13. Wonkmonk

    Wonkmonk Senior Member

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    Germany
    Many thanks for the explanation.
     
  14. greeneagledown

    greeneagledown Senior Member

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    Is it safe to assume, however, that drugs that are better at killing B-cells in lymph nodes and the spleen would be significantly more dangerous than Rituximab?
     
  15. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I suspect not. The idea is to clear out clones involved in a vicious cycle. Not quite completing the job may just teach the disease to box clever without significantly less danger. From what we know it seems that in some people rituximab does pretty much clear out all B cells. If that was in itself dangerous we would probably know by now. The main danger with rituximab comes from allergic reactions. The very rare risk of leucoencephalopathy has mostly been seen in lupus where if anything B cell killing tends to be less complete. So for the time being I do not think we have theoretical or practical evidence for more potent B cell agents being more dangerous.
     
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  16. greeneagledown

    greeneagledown Senior Member

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    Also, if it's impossible to tell how many of these "hidden" B-cells are being destroyed, how are drug companies going to know if the drugs they're developing are actually going to be better at targeting them?
     
  17. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    You can assay for B cell killing potential in tissue culture. You can also do experiments on macaques, which have almost identical B cell surface target molecules. More directly you can do dose response studies. For instance there is an antibody produced by another company that gives the same results as rituximab at half the dose, as part of a systematic dose response study. One of the problems with rituximab is that nobody did proper dose response studies for the sorts of b cells that are involved in autoimmunity (non-malignant ones).
     
    Gemini likes this.

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