Friday, 9 October 2015

ClinicSpeak: headline ocrelizumab results

The eagle has landed: ocrelizumab headline results. #ECTRIMS2015 #MSBlog #MSResearch #ClinicSpeak

"These are the results we have all been waiting and will almost certainly be what ECTRIMS 2015 is remembered for."

Data from the Phase III studies in patients with relapsing MS showed:

  1. A 46-percent and 47-percent reduction in the ARR compared with interferon beta-1a over the two-year period in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
  2. A 43-percent and 37-percent risk reduction in CDP sustained for 12 weeks compared with interferon beta-1a in OPERA I and OPERA II, respectively (p=0.0139 and p=0.0169).
  3. A 43-percent and 37-percent risk reduction in CDP sustained for 24 weeks compared with interferon beta-1a in OPERA I and OPERA II, respectively (p=0.0278 and p=0.0370).
  4. A 94-percent and 95-percent reduction in the total number of T1 gadolinium-enhancing lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
  5. A 77-percent and 83-percent reduction in the total number of new and/or enlarging hyperintense T2 lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).

The ORATORIO or PPMS study met its primary endpoint, showing treatment with ocrelizumab significantly reduced the risk of progression of clinical disability sustained for at least 12 weeks by 24 percent compared with placebo, as measured by the EDSS (p=0.0321). Additionally, ocrelizumab was superior to placebo in significantly reducing the risk of progression of clinical disability for at least 24 weeks by 25 percent (p=0.0365) and the time required to walk 25 feet (Timed 25-Foot Walk, or T25-FW) over 120 weeks by 29 percent (p=0.0404). Ocrelizumab decreased the volume of hyperintense T2 lesions by 3.4 percent over 120 weeks, compared to placebo which increased T2 volume by 7.4 percent (p<0.0001). Ocrelizumab reduced the rate of whole brain volume loss over
120 weeks by 17.5 percent compared to placebo (p=0.0206).



28 comments:

  1. BBC news website.
    http://www.bbc.co.uk/news/health-34475629

    First drug 'slows decline' in progressive MS
    The first drug to slow the decline in patients with primary progressive multiple sclerosis has been reported at a conference.

    The disease affects nerves and leads to fatigue, muscle problems and loss of vision.

    Preliminary data from trials of 732 people showed that ocrelizumab slowed the onset of disability by 24% over the course of 12 weeks.

    The MS Society said the findings were a "big moment" in treating the disease.

    ReplyDelete
    Replies
    1. Its was also posted on the MS Society website news page yesterday.

      https://www.mssociety.org.uk/ms-news/2015/10/first-phase-three-trial-show-positive-results-primary-progressive-ms

      First phase three trial to show positive results for primary progressive MS.

      Delete
  2. This is really sensational, I liked the comparison with the man stepping on the moon o// ... I don't have idea what the market value that Roche will play on Ocrelizumabe ... Surely many will $$$$ given the avalanche the drug in the "world of MS" ...

    ReplyDelete
  3. Do these results indicate that it is in the same efficacy league of Tysabri and Lemtrada ? How does it stand vs Gilenya ?

    ReplyDelete
    Replies
    1. Great then ! now hope they price it reasonably to increase patient access ..

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  4. I still don't get the results (brain fog ;-)) -

    so what does the drug do?

    Does it stop the 'pure neurodegeneration' in PPMS that has no relapses and no inflammation

    or is it just the PPMS with super imposed relapses so not really that great?

    ReplyDelete
    Replies
    1. They will not give us the answer I suspect but it is being presented today, it will be the first question asked , they will say no a dodge.

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  5. Surely if it offers improvement for PPMS, it should also be as effective for SPMS. Is that the case?

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  6. The results look similar to lemtrada for RR. If patients failed lemtrada would it be worth trying this drug (assuming it goes on to be licenced)? Does it work in a different way? The safety profile is better I understand.

    ReplyDelete
    Replies
    1. Anti-CD20 depletes B cells, Alemtuzumab is a B cell depleter but based on mouse studies it is not a good depleter in lymph glands and causes B cell autoimmunities

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  7. Hope of something with which to fight back a little. Remarkable. Simply remarkable. Man on the Moon indeed.

    But it should be a Swiss flag, I think?!

    ReplyDelete
    Replies
    1. The Swiss landed on the moon? ;>)

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    2. Whilst Roche is Swiss the antibody was made I believe from Genentech which is US-based and now I guess Swiss owned.

      Delete
  8. Man on the moon? Come on!

    This is merely a very small step. Keep it in check now. No hyperbole.

    ReplyDelete
    Replies
    1. A very significant step in the right direction. That people with PPMS - such as I - have been waiting for for a long, long time. And the only reason I am not ecstatic is that I think of those for whom this step, this new dawn of research in progressive MS, will be too late.

      Cynicism is simply not appropriate at this point.

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  9. and is there an exit strategy from this gear docs or is it a whoopsie like Tysabri ?

    ReplyDelete
    Replies
    1. What? Make sense, for goodness sake.

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    2. can you stop treatment or do you die as a result of stopping treatment as per Tysabri.

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    3. Not yet, it would make sense to plasma exchange if you need to remove the drug from the system quickly. From my previous use of rituximab in other autoimmune disorders there is reconstitution of the immune system and it would make sense to redose when this happens. Sometimes switch to another escalation therapy without the same side effect profile will also make sense.

      Delete
  10. 2 questions please:

    What is the likelihood that the results are replicated with SPMS ?

    What is the the impact on brain atrophy or how do these results (Ocrelizumab reduced the rate of whole brain volume loss over 120 weeks by 17.5 percent compared to placebo) compare to Alemtuzumab?

    Many thanks,

    Tony Fonda

    ReplyDelete
    Replies
    1. We need to see the results in PPMS but shoud be the same, but is it relapsing SPMS
      Not sure of alem atrophy data off top of my head

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    2. Here:

      http://multiple-sclerosis-research.blogspot.com/2015/04/aan-2015-alemtuzumab-brain-atrophy-data.html

      Tony

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  11. is this why this study succeeded ?

    > compared with placebo in 732 people
    > and a predefined number of CDP events was reached in the study

    ReplyDelete
    Replies
    1. I mean maybe ritux study lacked enough particfipantyears to show efficacy and here they got large group and awaited until they got accumulated predefined number progression events in their group to make sure difference is significant

      so is there any other things besides study design that is different between ritux studies and this?

      Delete

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