Monday, 1 December 2014

INFORMS STUDY: fingolimod in PPMS

Fingolimod in PPMS: MouseDoc 1 : ProfG 0 (HT score) #MSBlog #MSResearch

MouseDoc 1 : ProfG 0 (HT score)

"The informs study in PPMS did not meet the primary end-point. Let's hope the second-half has more to reveal."



CoI: multiple

23 comments:

  1. Does this mean you are no longer so hopeful that Gilenya will help in SPMS? Thanks

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    1. Gilenya is not being tested in SPMS, but this is Siponimod, but I do not think PPMS and SPMS will behave differently

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    2. i really think your attitude to the complete loss of hope to ppms'ers is disgusting.

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    3. It is what it is. We all wish it was different and we'd been proved wrong. Doesn't mean that other agents in trial for PPMS won't show some efficacy. I keep my fingers crossed.

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    4. It says" interpreting the good bad and other news" and to dress bad news up as good news will not do us any good.In relation to the action of immunosuppressive drugs in progressive MS, the writing has been on the wall for over 15years and thus bad news further
      reinforces this view. As to attitudes...I bite my lip

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  2. Well, that stinks. What study should PPMSers look forward to next? Ocrelizumab?

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  3. Unfortunately, we are going to have to wait until April 2015 when the data gets presented at the AAN. Novartis are unable to release any subgroup analyses. I was hoping the study was positive on upper limb function, which would support designing PPMS trials with better more responsive outcome measures.

    Don't give up hope; I am sure inflammation has a role in PPMS. Fingolimod may simply not be good enough as an anti-inflammatory. Ocrelizumab is a much more potent anti-inflammatory.

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    1. Clearly macrophage/microglia activity is involved in progressive disease. Maybe the trial designers should focus on how these drugs affect this aspect of the immune system instead of end points that have been proven over and over again to not show any result.

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    2. Pull the other one, Prof G. ait's it's got sleigh bells on it.

      It's another sad day for PPMS.

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    3. and when is ocrelizumab reporting results - in 2015?

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    4. I am a little confused on the timings for the drugs discussed:

      1. When in 2015 are the clinical results for fingolimod in PPMS released?

      2. When in 2015 are the clinical results for ocrelizumab in PPMS/RRMS released?

      Thanks for your efforts.

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    5. 1. As Prof G has stated April 2015 at the AAN meeting.
      2 Why not contact Roche, who are doing the trial?

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  4. "Unfortunately, we are going to have to wait until April 2015........." and so it goes. This theme seems prevalent in neurodegenerative diseases.

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    1. That is what Novartis said; April 2015 at the AAN. I had a call with them this morning asking for more data and they can't reveal any subgroup analyses.

      You need to remember that a subgroup of the rituximab PPMS trial was positive; it is telling us something important about PPMS. If it didn't do you think Roche would be doing a futile trial? Pharma companies tend to take well considered risks.

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  5. Prof G,

    they didn't mention anything about the secondary endpoints in the press release. Does this mean that the likes of the MR data is likely to be negative as well? If it was positive would there be any reason for them not to have announced that?

    many thanks.

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  6. Prof G,

    is there any mileage to be had out of a smaller trial with one of the apparently more effective DMTs versus placebo assessing microglial activity on PET scanning? Or studies including things like simvastatin and laquinimod versus placebo?

    If we think microglia could be important and potentially driving degeneration, why not look directly at them?

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    1. I think this could be a really good idea but will they rig the trial to show that you give the DMT so the condition does not allow the hot microglia to be generated or will they take a situation with hot microglial and then see if they can get rid of them. The latter is what is needed, but the former can put your drug in a better light in the short term.

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    2. The "Hot Microglia" theory seems to be a bust. Let's first find the culprit of the destruction.

      http://www.msdiscovery.org/news/new_findings/13483-innate-differences-demyelination

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    3. Seems to be a bust....Whilst this study is very interesting the right experiment to address this question has not been posed and I would not give up on the idea yet.....Simply look in MS and not Mice. Hot microglia/Hot Macrophage

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  7. It is so hard to keep up hope.

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    Replies
    1. The logic provided to support the neuroprotective effect was always strained but there are better candidates being tested

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    2. Is there any possibility that the RRMS/SPMS relationship is as simple as the relationship between rheumatoid and osteoarthritis where those that have the former are predisposed to degeneration in the form of the latter after the inflammatory phase has burnt out? (though the analogy falls apart a bit when you look at OA on its own) This would bode much better for those diagnosed with 'treatable' RRMS than those who slip into SPMS (and again poorly for PPMS, if it does represent SPMS following clinically silent RRMS).

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