The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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New multiple sclerosis drug can 'cut relapses by nearly 50%'

Discussion in 'Other Health News and Research' started by Bob, Oct 8, 2015.

  1. Bob

    Bob

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    This seems like quite a major development for MS. Results of phase iii trial for MS using Ocrelizumab (a humanized anti-CD20 monoclonal antibody.) The therapeutic benefits described below are in comparison with existing treatments rather than no treatment, so they seem very impressive.

    New multiple sclerosis drug can 'cut relapses by nearly 50%'

    http://www.theguardian.com/society/...-sclerosis-drug-can-cut-relapses-by-nearly-50

     
    Last edited: Oct 9, 2015
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  2. Bob

    Bob

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  3. Bob

    Bob

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  4. barbc56

    barbc56 Senior Member

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    I'll pass this on to my step mother as she has MS.

    Thanks.

    Barb

    ETA I didn't see that the drug is for progressive MS. She has relapsing/remitting form of MS. Fortunately, she is doing well but does tire easily. I can relate to that.
     
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  5. Bob

    Bob

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    I'm not sure if I've understood you correctly but the drug is for both types of MS. The article emphasises progressive MS because it says there's not a treatment available for that currently. For relapsing/remitting MS, it says it can cut relapses by nearly 50% more than current treatments. (It's not a very clear article.)
     
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  6. barbc56

    barbc56 Senior Member

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    Somehow, I missed that. I have to admit I read it in a hurry but intend to read it more throughly later. I did catch that it helps with relaspes, but I processed it as for progressive MS. Thanks for the clarification.

    It's great we can rely on one another to sift through this fog. :)

    Barb
     
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  7. Valentijn

    Valentijn Senior Member

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  8. Bob

    Bob

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    Two other thoughts/questions...
    Has rituximab never been trialled with MS patients?
    And would Roche like to carry out a large trial of Ocrelizumab for ME patients?
     
    Last edited: Oct 9, 2015
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  9. Bob

    Bob

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    Low side effect profile...
    http://www.roche.com/investors/updates/inv-update-2015-09-28.htm
     
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  10. Sidereal

    Sidereal Senior Member

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    I understand that the development of this drug was halted a few years ago in RA and SLE due to deaths from opportunistic infection.
     
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  11. Sidereal

    Sidereal Senior Member

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    Medscape write-up on primary progressive MS trial:

    Fairly modest results but when you consider how catastrophic PPMS is and how there is no treatment for it, any benefit is surely welcome.
     
  12. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Ocrelizumab is very similar to rituximab and was developed as a way of getting around the patent lifespan problem, showing some rather marginal advantage in B cell killing if I remember rightly. There are now what look like significantly better antibodies coming along but ocrelizumab is what Roche has been taking forward in development. It is essentially the same as rituximab but probably slightly more potent.
     
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  13. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    And yes, I was forgetting that ocrelizumab is human rather than chimaeric but in reality because these drugs deplete the B cells that might make anti-antibodies (HACA or HAMA) it is doubtful whether humanisation is a big deal here. Killing efficacy is what matters - and particularly killing of hidden poopulations that might be untouched by rituximab.
     
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  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I am unclear why ocrelizumab has not been progressed for RA. I think there was a rather disappointing trial at one point and it may be that the company decided to reap the benefit of rituximab in what is a relatively small part of their market for B cell antibodies and not spend money developing ocrelizumab for everything. (Roche knew they had even better looking antibodies coming on stream around that time.) Clearly they have taken it forward for MS. The problem with lupus was that an early trial with rituximab appeared to show no benefit - probably because of poor design. Many lupus physicians use it and I have seen dramatic responses to it in lupus. So over the last ten years I am not sure any CD20 antibody has been progressed in lupus. That is now changing with combination therapy trials.
     
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  15. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I think the results may look modest simply because once the disease has established the best you can hope for is some damage limitation. Scoring systems often have a 'glass ceiling' beyond which in practice you cannot get. What will be important to see is what happens if patients are treated within days of their first clinical presentation.
     
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  16. Sidereal

    Sidereal Senior Member

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    There were two large RCTs of rituximab for lupus and neither of them met the primary endpoint. The issues with design of those studies are discussed in this review paper. They also discuss the positive results from clinical practice and uncontrolled, open-label studies.

    As for ocrelizumab in lupus and RA, here's a press release: http://www.roche.com/media/store/releases/med-cor-2010-03-08.htm

     
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  17. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Yes the review paper came from my department - and the optimism was based on the lupus patients I entered into the first lupus study carried out by my PhD student Maria Leandro (they were under the overall care of David Isenberg) and continued usage in the department. Venkat Reddy is still doing a PhD with us on new anti-CD20s. I don't put my name on papers these days.

    I would take the press release with a pinch of salt. The US rheumatology community never liked the idea of rituximab for RA because they did not get much in the way of infusion fees (this was said quite openly at the first general advisory board when my phase 2 data showed it worked). Genentech subsequently have put out frankly frightening information sheets for rituximab for RA. Presumably because they do not want to be sued. I am aware that one particular trial with ocrelizumab caused the companies a problem, which may have been an infection signal. But I am doubtful that across the board there is evidence for ocrelizumab being different from rituximab in this respect. There will have been opportunist infections in lupus because seriously ill lupus patients are full of opportunistic infections anyway. There was also some head scratching when a tiny number of people developed PML.

    These drugs routinely get mothballed apparently for medical or scientific reasons when the real reason is commercial. I may be wrong but if they really thought ocrelizumab was dangerous it would be odd that they are pursuing it in MS.

    I have a suspicion that ocrelizumab is going to be irrelevant to ME anyway since the data so far are with rituximab and if companies want to move on from that it will probably be something further down the development line or from a different company.
     
  18. Sidereal

    Sidereal Senior Member

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    Very interesting.

    Yeah, the PML stuff seems vastly overblown. From what I've gathered, two patients with lupus died of PML on rituximab but they were also concurrently receiving their regular immunosuppressants.

    Regarding the trial of ocrelizumab (ludicrous name, btw) which showed an infection signal, is it this one on lupus nephritis which was terminated early?

    http://www.ncbi.nlm.nih.gov/pubmed/23740801

    What struck me as odd about this is that the patients on 400 mg of ocrelizumab had more serious adverse events and serious infections than the patients on 1,000 mg. The patients who were on 1,000 mg of ocrelizumab had fewer SAEs than the ones on placebo.
     
  19. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    All I can really remember about this episode is that a trial flagged up a problem but, as you say, it did not seem to make much sense. That made me think it was a fluke problem. But it's a long time ago now. A bit like trying to figure out who shot Jack Kennedy.
     
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  20. Sidereal

    Sidereal Senior Member

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    It does indeed look like a statistical fluke. They saw the infection rate, freaked out and terminated the trial early. Obviously, the problem is that they were only powered to detect a difference on the primary outcome measure (efficacy), not on these secondary outcomes, so whether the difference in rates of side effects is real is more of a judgement call. Of course if a ton of people are dying in one arm of your trial you'd stop early but these data look indeterminate to me. There is no dose-response relationship which makes me further question their interpretation, although I don't know jack about immunology so for all I know there is some plausible biological mechanism by which high dose of a drug could cause fewer serious adverse events than placebo while low dose of the same drug could cause more serious adverse events than placebo.

    Oh well, as you say, it's all ancient ancient history anyway.
     
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