Tuesday, 30 June 2015

Alemtuzumab, here I come: Top line results of the Ocrelizumab in relapsing MS studies

This morning, Roche announced the headline results of their Ocrelizumab in relapsing MS program (OPERA I and II).   Here is their press release:


Numerous posts on this blog have highlighted the potential of this humanized version of Rituximab (check the "BartsMS essential off-label DMT list" in the left upper corner), an established drug to treat people with B cell lymphoma, for the treatment of people with MS. Ocrelizumab appears to be significantly better compared to interferon beta, however is it as good as alemtuzumab but without the significant risk of autoimmunity?

36 comments:

  1. Out of interest, marketing/price/patent aside, what is the difference between Rituximab and Ocrelizumab?

    Do they have similar efficacy in term of wiping out B cells?

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    1. Rituximab is a chimeric antibody the variable region is mouse the constant region human
      Ocrelizumab is humanised so only the complementary determining region (target binding) are mouse and Ofatumumab is totally human and sat on a shelf...will it be moved now.

      Functionally they are the same.....The question will be the price....they will want every 6 month dosing or an induction therapy.

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    2. MD, when do you think they will present detailed result? Do you think this therapy could eventually stop MS in his track ?

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    3. i am guessing it will be like alemtuzumab without the symptoms

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    4. Data to be presented at ectrims 2015

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  2. Good results were expected , beating inf beta also a given ..no data ? ..will it outperform Tysabri and Alem ?

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    1. no autoimmunity like lemtrda lower pml frequency i guess

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    2. Sounds so good ! , can't wait trial results ..

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  3. Dear B cells,

    I want to end our relationship.

    It's not you its me, I feel that you participate in an attack against me for no good reason. We've had a long time together but I think that you need to leave.

    -Aidan

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  4. Would this be useful in PPMS for the initial or any secondary inflammatory action?
    Or is this another purely RRMS drug, that the headline makers will state 'cure for ms' but forget those who have progressive disease

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    1. The progressive trial is finished nexf year. Based on rituximab i would predict no effect on nonrelapsing disease but positive effect on gadolium enhancing

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    2. Then why are they waiting to file until 2016? I think they know the trial is positive for ppms and want to file on both rrms and ppms. Obviously reading tea leaves here but would think they would want to get to market asap otherwise.

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    3. I was thinking the other way round - they're probably starting to see that effects on ppms are either marginal, or not observable this far in. Otherwise, I'd expect to see some hint of positive data being collected. You'd think they'd want to back up the positive RRMS data with some suggestion that there was more good news to come, if they are presenting for shareholders. Look at how over-inflated the Biotin stuff was, before the data for it was released.

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    4. It blows my mind that incredibly powerful anti-inflammatories like Rituximab & Ocrelizumab don't seem to affect the low-grade inflammation typically associated with progression, yet something as benign as aspirin does seem to have an effect (even if only a subtle one).

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    5. Me too. The only thing with aspirin and ibuprofen is stomach problems. Even taking enteric-coated still causes bloating and constipation. But they do appear help with low-grade inflammation and also heat intolerance for me, and perhaps because of helping with low-grade inflammation and humidity, it also seems to help my cognition too. I don't take aspirin all the time, because of the stomach problems but enough to see a difference in cognition.

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  5. These press releases are irritating, especially if there is a large gap between this and seeing the actual figures.

    Obviously they've analysed the results if they've decided to put this out.

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    1. They are telling shareholders good news so this is a business announcement not a science one. They course know the result

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    2. Likewise the importance is not when they announce the result the importance is when the regulators announce what they are going to do in terms of approval and the company will be working on this and I bet have been working on this waiting for the trial results. Remember time is money.

      I guess there will be an investigators meeting when the neuros involved will be told of the result, is this going to be in Switzerland or US?

      ProfG will know but is probably not allowed to say anything..The meeces are kept in the dark:-(

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  6. How is it no one knows that causes orogressive disease or indeed how to stop it?
    One would think it would be an easier target than an inflammatory stage?

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    1. please read through the blog or some answers and solutions

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    2. Great answer mouse

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  7. What are the implications of the high efficacy of anti CD20s on the science and what we think we know about MS pathogenisis ?

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    1. That the sole focus on T cells by the immunologists was misplaced and we've all been guilty of that to a greater or lesser extent over the years. If ocrelizumab is as effective as alemtuzumab at stopping relapses without the development of secondary autoimmunities, the alemtuzumab is finished. The same for Tysabri if PML isn't a problem.

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  8. Anon 7:28 - have a look at this link: http://multiple-sclerosis-research.blogspot.com/2015/04/aan-2015-embargo-lifted-early-on-optic.html

    It's not an iron-clad guarantee that sodium channel blockers are the key to progressive MS, but the evidence thus far is pretty compelling, and it looks like the mice have done their homework. They make a pretty persuasive argument that this approach will likely save nerves.

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  9. This is all good and well but where next? They've proved that the drug has to be given early so why is there not more bejng done for those with the disease now
    Is there further trials planned yet? When is this theory expected to be brought to the patients

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    1. The soonest it is being brought to patients is now.....at the Barts and the London. Sign up to PROXIMUS.......DMT + Sodium Channel blocker....Oxcarb wiped the floor with phenytonin.

      The problem for sodium channel blockers is their potential for side effects, especially in people with demyelination...We believe there are solutions.

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    2. MD, great science on your guys' part with the whole sodium channel blocker thing (seriously, well done). But I'm curious why you think that side effects would be worse for people with demyelination than for people without demyelination. Are you talking about the same side-effects as other folks, but just more likelihood of having them? Or totally different & new side-effects than those that have been seen in non-MS populations to date?

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    3. This is the reality the lamotrigine trial filed because 50% of people were not taking the drug. In health the sodium channels are concentrated at the nodes of ranvier which is the space between the myelin sheaths. When you have demyelination you get alot more channels because you need them to keep the nerve working, so blocking them can cause a number of problems including movement problems

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  10. Of note, I have a significant amount of experience with rituxan in off label in relapsing multiple sclerosis (> 200 patients), and I can tell you that mild infusion reactions are common, but serious infusion reactions are quite uncommon. Achieving undetectable b cell counts for 6+ months is common with rituxan. I doubt there would be any significant safety or efficacy improvements with ocrelizumab or ofatumumab, though ofatumumab is an anti CD19 agent. However, CD19 and CD20 counts are often identical, suggesting a very strong overlap (there are not many CD19+CD20- cells floating around). My experience concurs with what mouse doctor suggests-that rituxan is not effective in non-relapsing progressive multiple sclerosis which is radiologically silent. In the OLYMPUS trials (rituxan and PPMS), there was a signal in the post-hoc analysis were those who were < age 50 and had Gad+ lesions did better than placebo which is logical.

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    1. Thanks for this insight

      I am pretty confident that Ofatumumab (trade name Arzerra, also known as HuMax-CD20) is a GSK or Novartis (or cancer) anti-CD20 and not an anti-CD19 antiboy.

      The anti-CD19 antibody in trial inMS is MEDI-551

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  11. If it wasn't safe enough for RA pts, why should it be safe in MS Pts?
    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087379

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    1. If we look at risk benefit.

      Ocreluzimab development was terminated in RA due to death due to infections. In RA is you fail to treat and you get damage you can replace a joint, but in MS you cannot replace a brain. So someone with MS will take more risks than someone with arthritis. Likewise if you have cancer that may kill you you will take more risks that someone with MS

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  12. Rituxan is very good at suppressing relapses.

    What happens after that -- does it keep patients stable after the relapses stop?
    Or does it perhaps convert RRMS into a variant of PPMS?

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  13. I suspect it depends on how early people start after diagnosis at some point there may be people going progressive. The question is what is that window of oppertunity to achieve maximal effect.

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  14. Is ocrelizumab a life long treatment as interferons.....?

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