Friday, 12 January 2018

Newsflash: the wait is over ocrelizumab finally gets its EU marketing authorisation

If you have PPMS, and live in Europe, you are one step closer to having a disease-modifying therapy for your MS.



If you have PPMS and live in England you have to wait for NICE to determine whether or not ocrelizumab is a cost-effective treatment to slow down your disease progression.  To help manage expectations I anticipate NICE saying no for the PPMS indication. Ocrelizumab will be priced for the RRMS indication and not PPMS. The impact of ocrelizumab on disease progression is less in PPMS compared to RRMS and because it will be compared to 'best supportive care' for PPMS it is unlikely to be deemed cost-effective. One solution to this impasse is for differential pricing, i.e. for Roche to charge the NHS much less for PPMS compared to RRMS. Is Roche and the NHS ready for differential pricing? I am not sure. However, the NHS accounting mechanisms are in place to do this. It will be interesting to see how the NICE negotiations play out.

EMA information on ocrelizumab.



ProfG    

45 comments:

  1. If NICE don't approve for PPMS perhaps this would be a good opportunity to promote off-label cladribine for everyone with worsening MS.

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  2. It would be cruel for NICE to deny PPMSers Ocrevus. At least give it to those in the early stages if you can't afford to give it to everyone! I would like to see how NICE would react if they were given such a diagnosis.

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  3. If NICE don't approve for PPMS perhaps we can reassign everyones disease as RRMS . as they are all one disease these days!

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    1. I agree, I'm 25 and newly diagnosed with PPMS! How could they be so cruel?

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  4. Approved for RRMS not for PPMS......just semantics, as you have said there is just MS period.

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  5. What hope is there for PPMS?! I'm 25, is there any hope or should I just quit while i'm ahead?!

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  6. "If you have PPMS",
    "the RRMS indication and not PPMS"

    "This tells you that MS is one disease and that if we can diagnose and treat MS in the asymptomatic phase we may be able to delay the onset of PPMS. "

    Could you explain sometimes i get confuse ,you say one thing and

    after a while you say another

    Obrigado

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    Replies
    1. Although Barts-MS takes the position that MS is one disease, this is not the position of the wider MS community, including the regulators, NICE and the NHS.

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    2. This should be an important topic of discussion at ECTRIMS whether MS is one disease or not as it affects treatment options. I think proponents of classifying RRMS, PPMS, SPMS would argue that adaptive immune activity and BBB permeability are more characteristic of relapses and progression is defined by glial cell activity inside the CNS.

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  7. I understand why barts is tryingn not to get ppms patients hopes too high. But i find it hard to believe nice will follow different path to fda and ema. Only if they are negotiating the price down. I am 100% sure they will approve for ppms. As much as they are ruthless i find it hard to believe they will deny the only drug approved for ppms. So stay positive.

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    1. I thought this too, how can they deny PPMS patients the only slither of hope that has ever been presented to us? Surely there's no way that they won't follow fda and ema.

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  8. I'm 22 with PPMS in England, just diagnosed. Ocrevus is obviously my only hope. Is there ANYTHING else on the horizon that could help me? I'm so young and am scared I won't be able to have a life without any treatment! What else is there?

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    1. @Iz and Anonymous Friday, January 12, 2018 10:50:00 pm

      There is Ocrevus/Mabthera (off label) but also Cladribine and HSCT could help you (maybe even more). Thinks are moving fast these days and there are more things coming for the progressive forms of the disease.
      Its hard to get such a diagnosis but its there is some light in the darkness.

      @Barts Since there is no other official treatment for PPMS I believe (hope) that NICE will not see the statistics. Only Canada hasn't approved yet for PPMS but it is expected to happen.

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    2. Would Cladribine work for PPMS? Is there no way that a neurologist could prescribe Ocrevus even despite NICE's ruling?

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    3. Hi Iz and Anons with PPMS
      Please don't despair you are too young to lose hope.
      1. NICE may approve ocrelizumab. Hang on in there, not long to wait.
      2. As I understand it, MS is one disease and cladribine off-label will be effective.
      3. NHS are ok with off-label cladribine as it is relatively cheap. Off-label is justified when there is no licensed treatment available. So you need to wait for ocrelizumab decision first.
      4. If NICE say no, ask your GP to refer you to another neurologist if you get nowhere with yours re cladribine. Ask for referral to Barts?
      5. Are you confident of your diagnosis? Second opinion?
      6. Pray for a relapse! Only half joking, bloody annoying this dividing MS into arbitrary different diseases :(

      Never give up! There will be more treatments..

      Very best wishes AM :)





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    4. Hi AM, thanks so much! Trying not to lose hope, it's just incredibly scary! And yes unfortunately we're certain of my diagnosis. I'm furious!

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  9. Despite what Prof G & co say, the experts haven't got a clue what is driving progression. I see that Pfizer are pulling the plug on Alzheimer's research. Why? Because 99% of trials over the last 15 years have failed. We were sold a pup with Ocrelezumab for PPMS. The effects of the drug is minimal and only for a subset of patients. What do patients want? To stop progression / increasing levels of disability. What do the experts give us? A drug which has a mild effect on slowing down the accumulation of disability for a minority of patients. We have used the term expert too loosely for MS researchers across the world. An expert knows everything about their subject. We are years away from really effective drugs to STOP neurodegenerative diseases. Until the so called experts understand what they are dealing with, there will be no real advances.

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    1. Sorry you are wrong.

      We have lots of clues what is going on, the issue is how best to deal with the clues we have, as you suggest trials take a long time and we need agents to target important pathways...they don't just magic themselves into exsistence I'm afraid.

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    2. Many have sadly passed away on MS meds that's being hushed away .

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    3. Pharma invests like crazy on Altzheimers - Parkinsons, so it is a little arbitrary to suggest that Pfizer pulled back because neuroscience is miles away from positive results. It could be just that Pfizer sees that their drug isn't as good as the rest so it doesn't worth to invest.
      An diabetes drug had positive results for Altzheimers lately (a diabetes drug had been found to help the course of MS too). Will it ever be licenced for Alzheimers with all these invests on new drugs? You can never thust Pharma.

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    4. Please could you clarify - Anonymous Saturday, January 13, 2018 4:03:00 pm - where you found out that 'many have sadly passed away on MS meds'? How many deaths and which drugs were involved?

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    5. Mouse, clues and ideas are of no value to someone diagnosed with SPMS or PPMS. Where are the neuroprotectives? What happened to the work of Dr Kapoor? Where is Team G in the field of neuroprotection? I'm not picking on Team G, but Bristol, Cambridge, Edinburgh, Glasgow. All have MS research units which are considered world class, but none have addressed progression. Year after year goes by and trials never deliver effective treatments - trials based on the theories and ideas of researchers. Pi** Poor sums up the progress to date by the world of MS research. How many more ECTRIMS / ACTRIMS conferences must we have before the cause of MS is identified / agreed and effective treatments for progressive MS are delivered to the patient?

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    6. Anon 4.03 4.04
      To put it in perspective: many more people have passed away from MS.

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    7. "Please could you clarify - Anonymous Saturday, January 13, 2018 4:03:00 pm - where you found out that 'many have sadly passed away on MS meds'?"
      Don't bother asking this question, this person posts the same comments day after day. These 2 slipped past the moderation process (there are hundreds of similar posts in the spam folder).

      Delete
    8. Anonymous Sat 7:45 pm
      All the neuroprotection studies thus far have been without the involvement of pharma so progress is as a result painfully slow as these studies cost a lot of money and the pot is limited. It's a source of huge frustration here at team G as we have been perhaps the leaders in identifying potential neuroprotectives for MS but the challenge of getting from the bench, where we have abundant data to the bedside is very difficult. Not that long ago pharma wasn't interested in MS but that has changed greatly however, their focus is solely directed at treating the immune mediated aspect of MS. We have shown that just focusing on this aspect is not good enough for many but until they also decide neuroprotectants are also important (and they can make money from such a strategy) we are limited. So from a researcher's perspective, it isn't for the want of trying.

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    9. Can I ask what neuroprotectives sound promising to Barts?

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    10. MD 2, many thanks for your response. I'm not trying to undermine the hard work of research teams, but understand the reasons why we still have no neuroprotective therapies given the work of researchers such as Dr Kapoor (a researcher who I know has done a lot of work in this area). Research is published which looks promising, alliances are formed to propel research forward.... The patient never seems to get a treatment which stops nerves from degenerating further!

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    11. you're welcome. We're as frustrated as you are, part of the reason is that studies such as performed by Dr Kapoor etc (stimulated by research here without pharma support) are limited to using agents that are already licensed for use in other areas (such as phenytoin and lamotrigine for epilepsy). This is also the case with the PROXIMUS study which again is looking at Oxcarbazepine, again an agent used for the treatment of epilepsy. Experimentally, oxcarbazepine showed a very good neuroprotective potential but will have some negative side-effects which may lead to non-compliance. To my mind it is sad that the CUPID trial for
      cannabis effects on progression (again building on our research) was viewed as a failure (due to a variety of reasons) as it was clear in a sub-group of pwMS it was clear that there was as effect on the slowing of progression in this group but sadly this is not likely to be taken forward now. So, progress is frustratingly slow and until pharma gets properly on board it seems it will remain slow but the potential is undoubtedly there and once pharma realises they can make money in this area they will, eventually climb on board but perhaps ten years too late.

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    12. Please could you clarify - Anonymous Saturday, January 13, 2018 4:03:00 pm - where you found out that 'many have sadly passed away on MS meds'? How many deaths and which drugs were involved?

      Sorry this escaped the spam filter it will be from our mate in Leicester.

      It should be in spam...Say this is censoring if you like, but (a) it is not supported by evidence and there a hundreds of such comments in spam they arrive often daily.

      The number of deaths of ocrelizumab and any other drug is reported in USA are reported as are those in EU.

      Delete
    13. Totally agree with MD2.

      The trial designs have been a problem. It is very frustrating for us.Many years of our lives and research avenues are thrown in the bin by a failed trial.

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    14. Sorry mouses but from your comments on this and other threads, it does not sound like you are as frustrated as the patients (nor can you be lol).

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  10. Is it really better?

    "Nonetheless,
    ocrelizumab infusions in MS patients appear to be related to elevated risk of upper and
    lower respiratory infections, upper respiratory irritation during the infusions (typically the
    first infusion), peripheral herpes related infections, and some concern over malignancies, particularly
    breast cancers [25]. In terms of rituximab, such adverse events were not seen in our
    study or in prior studies. These differences in the profile of adverse events may highlight fundamental
    differences in the pharmacokinetic and pharmacodynamic properties of the two
    molecules, which remain to be explored. It is already known that the two molecules have differences
    in the mechanism whereby they achieve B-cell depletion. There may be important difference
    in tissue penetration, repletion rate, and secondary effects on T-cells"


    Long-term safety of rituximab induced
    peripheral B-cell depletion in autoimmune
    neurological diseases

    https://doi.org/
    10.1371/journal.pone.0190425

    Obrigado

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  11. I have a question! If Ocrevus reduces the risk of progression by 25% for some patients, does that mean that there is a 25% chance that you WON'T progress while on Ocrevus? (Very small chance, but do I have the right Idea?)

    Thanks docs x

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  12. it has been stated and I quote Dr Giovannoni here that with cladribine it is "just 8-10 days of treatment in year-1 and a repeat cycle year-2 is sufficient to put the majority of subjects into long-term remission for up to 4 years and beyond". I have some questions on this for the doctors at Barts with experience with using cladribine: 1) in case of those blessed patient completing the 4 years treatment with cladribine and going into long-term remissions what is the clinical exit strategy for them? in other words how are they treated following successful treatment with cladribine? 2) what happens to patients on cladribine if they have a relapse within 4 years of treatment? will they need to step up and escalate therapy? 3)is it possible to re-use of cladribine if a patient has previously relapsed on that in previous treatment lines? it is highly likely it is not logic to re-use but it would be good to hear that from who had experience with that....thanks

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    1. I am not a Doctor and have no knowledge who Merck expect it to be used for disease breakthrough and I have no conflicts of interest

      First things first but if you look at the trial data, you have to expect that about 50% of people will show some form of disease activity in the first two years, just like you get with alemtuzumab and ocrelizumab it is not infallible.

      There will be people who break through before and after 4 years just like occurs with alemtuzumab. The reason why people are reporting 4 year influences is because they have trial data on that the 2 year tiral and the 2 year extxtension study. For people it works well in they may not need retreatment...they may.

      If you have disease activity with alemtuzumab you can get a further treatment if you can get your health payer to pay for it you can have a third course. There is is no reason to expect that this will not work again and unlikel alemtuzumab where neutralizing antibodies dictate when you can retreat this will be less of an issue with cladribine as it is not a protein drug.

      Obviously if disease is very active you may need to change if it is not working.

      In UK I dont know if NHS will support a third treatment cycle if they dont there is generic cladribne which could do the same thing.

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  13. it has been stated and I quote Dr Giovannoni here that with cladribine it is "just 8-10 days of treatment in year-1 and a repeat cycle year-2 is sufficient to put the majority of subjects into long-term remission for up to 4 years and beyond". I have some questions on this for the doctors at Barts with experience with using cladribine: 1) in case of those blessed patient completing the 4 years treatment with cladribine and going into long-term remissions what is the clinical exit strategy for them? in other words how are they treated following successful treatment with cladribine? 2) what happens to patients on cladribine if they have a relapse within 4 years of treatment? will they need to step up and escalate therapy? 3)is it possible to re-use of cladribine if a patient has previously relapsed on that in previous treatment lines? it is highly likely it is not logic to re-use but it would be good to hear that from who had experience with that....thanks

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  14. Since we are into videos lately...

    Ocrevus (ocrelizumab) Mechanism of Action
    https://www.youtube.com/watch?v=Pco9l6gcR4w&feature=share

    3D for MD ;)

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    Replies
    1. I can't wait to see this.
      I'm expecting antigen presentation, B cell follicles and cytokine inhibition which is the usual guff. When I see it will I've surprised.

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    2. Yep no surprises....and yep no real insight. It give the stock view with a few inconsistencies

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  15. MS Trust Seeking PPMS Patients' Views on Ocrevus as It Tries to Obtain British Coverage
    https://www.surveymonkey.co.uk/r/ocrelizumab-for-PPMS

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