Wednesday, 14 December 2016

#ClinicSpeak & #ThinkHand: famine to a feast

Are there enough progressive patients to go around? #ClinicSpeak #ThinkHand

Since the half-positive natalizumab in SPMS (ASCEND), positive ocrelizumab in PPMS (ORATORIO), and positive siponimod in SPMS (EXPAND) trials there has been an explosion of interest in doing trials in progressive MS. I have recently been engaged in so many discussions with investigators planning investigator-led, or with pharma representatives, planning large-scale phase 3 trials, that I am now concerned that we don't have enough 'clean' patients with advanced MS to recruit for all these trials. Clean refers to the pwMS without a significant prior treatment history or comorbidities that makes them eligible for progressive trials. The screen failure rate for progressive trials is much greater than with relapsing studies. We seem to have gone from a famine to a feast.

The problem will be compounded by indication creep, i.e. extending prescribing from relapsing MS into SPMS and from PPMS into SPMS. I am not surprised by the latter; it is clear that our definition of what is progressive MS, is so nebulous, that it actually encourages indication creep. What can we do about this? I think we should scrap  the artificial definition between relapsing and progressive MS and tell all our patients that regardless of what stage of the disease they think they are in their is the potential for them to have progressive, or more correctly, neurodegenerative pathology already. We should then be targeting this pathology regardless of phase of disease. We should also be extending the window to beyond the mobile phase of the disease and including wheelchair-users in trials. The arguments for the latter are now overwhelming and underpins our #ThinkHand campaign.

Is this good news, or not, for people with more advanced MS?


CoI: multiple

9 comments:

  1. I'm a pwPPMS, "clean" as defined, when and where do I sign up?

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  2. Should investigators be doing phase III trials? They never go anywhere?
    Statins a good example so called positive and that was years ago.

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    Replies
    1. I have some sympathy with your view, though sometimes an investigator led trial might kick start activity in a new area, hopefully this will happen in the search for efficient neuroprotective therapeutics in MS. So perhaps the jury is still out. As you're well aware these things take a very long term to come through, I wish it could be quicker.

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  3. It is a great news. Pharmas do not want Roche to eat the entire cake all alone... But at the end of day it means eventually more drugs and better care for progressive MSer. It is also hope for all others at earlier stage of the disease.
    Trial population, although "the best", should reflect the real patient population in needs and pharmas have the possibility to organize recruitment centers in many countries.
    Thanks to continue challenging pharmas to open this to wheelchairs MSer. Could we find some "clean" patients or "close to clean"? Eventually, it could speed their recruitment & time to market...
    This is all about pertinent clinical end points and close relationship with regulators. And risk taking for sure, not everything will work.

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  4. If these trials are placebo-controlled, hardly anyone will enroll, at least in wealthier countries. In US, prob most people not having relapses still take DMTs.

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    Replies
    1. Re: "...If these trials are placebo-controlled..."

      Yes, many of these studies will be placebo-controlled.

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    2. why do you need so many placebo controlled trials? can't you get close enough with the new article published from msbase... there are a couple of other world wide registries - why not use the existing data?

      i don't have the msbase article to hand, but it was released recently and talks about the effect of immune modulation on more advanced MS - i'm sure you're aware of it.

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  5. Will Ocrelizumab change the MS drug market? So will it bring a safety induction therapy?
    When will scientists prove or diprove it? (Years or decades?)
    Will this studies reshape the current progressive MS paradigm so will OCR a 'Progressive MS drug' (not only PPMS).

    These are very BrainVolumeLoss Questions for people with MS (RR and Progressive too)...

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  6. What can we do about this? I think we should scrap the artificial definition between relapsing and progressive MS and tell all our patients that regardless of what stage of the disease they think they are in their is the potential for them to have progressive, or more correctly, neurodegenerative pathology already. We should then be targeting this pathology regardless of phase of disease.

    Conversation between my partner and a neuro 18 months ago:

    Neuro: I think you should take Tysabri.

    My partner: I want XYZ, for XYZ reasons... it should work as well as tysabri but i'm too tired to have ongoing infusions: i have done that with cancer for 5 years, i can't do it again if there is an alternative.

    Neuro: XYZ doesn't work for progressive MS.

    Me: she doesn't have progressive MS.

    Neuro: she's never had a relapse.

    Me: she's never identified or felt a relapse, but she has lesions.

    Neuro: none of the lesions are enhancing.

    Me: One is.

    Neuro: oh it's small.

    Me: anyway, can we move on: this is pointless. If you are recommending Tysabri then you're not doing it for 'progressive' MS, we want to know about XYZ - what can you tell us.

    Neuro: It doesn't work for progressive MS.

    Me: for fuck's sake: what planet are we on? (not an exact quote of my response).

    ReplyDelete

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