COVID Breakfast. Mousey Shark

C

ProfG warned about not being an Ostrich in case you get bitten in the Arse/Ass.

So all together.

Mousey Shark Do Do…Do…DoDo; Mousey, Mousey Shark DoDo…Do…DoDo; Mousey, Mousey Shark DoDo…Do…DoDo; Mousey Shark

The CD20 wars are going to ramp up and COVID-19 could be just one battle ground that makes the difference. Ocrelizumab has been flying high in the MS_DMT charts. You know Pharma they like a slice of the pie and they hunt in packs

Here we go….Pharma Shark Do Do…Do…DoDo; Pharma Shark DoDo…Do…DoDo; Pharma Shark DoDo…Do…DoDo; Pharma Shark

The makers for ocrelizumab and rituximab are also the makers of a machine that goes ping and have FDA approval to test antibodies against SARS-CoV-2. Therefore they are a perfect place to monitor all their patients on ocrelizumab/rituximab to see if they have made an anti-viral response. Are they going to do it…probably they will have to because if they don’t someone else will do it…But would you trust them?

After all they have done vaccine trials and despite being reported they have not published their in a Peer-reviewed journal, possibly because surprisng surprise, your vaccine responses are not that great. Rule number 1 in Pharma land…don’t SH1 on yourself.

So here we go Mousey Shark Do Do…Do…DoDo; Mousey, Mousey Shark DoDo…Do…DoDo; Mousey, Mousey Shark DoDo…Do…DoDo; Mousey Shark

We have predicted that you don’t need B cells and antibody to get did of the virus, but immunology 101 says it is part of the defence machinery and the important point is what happens next time you get infected. If you have an intact immune response and viral immunity, nothing happens or the symptomatic problems are blunted.

In Monkeys re-infected they showed mild symptoms for a day and the virus was gone. If fact it never got started and these monkeys all had a rip-roaring antibody response

Now the World Health Organisation have started to cause SH1 by saying don’t issue anti-viral passports because we don’t know if immunity will stop re-infection, but immunology101 says this can happen and what evidence is there that you can get re-infected and show severe symptoms?.

We have heard alot about finding virus again, but the simple logic is this is not a re-infection but the infection never went away…we know you are producing virus for over 2 weeks after you have not been sheeding from your nose. I know someone who when to hospital twice once for 3 days and then about a week later for a week. Had they been re-infected? I doubt it. Do people harbour more than one virus I have seen evidence of this. Maybe wrong you can give me the references as oposed to the newspaper cuttings

So the question is if you are B cell depleted will you show re-infection and can you mount an anti-viral B cell response and if you do is it good enough. Why the concern because people treated with rituximab have a reduced vaccine response and this occurs with ocrelizumab too. This may be important if a COVID-19 vaccine occurs

This is the response to a pneumococcal vaccine NCT02545868

Does this surprise me. The anwer is no. This because there is marked depletion of the B cells that are going to make the new responses. If you stop ocrelizumab these take about 60-70 weeks to recover. The question is how many do yu need to give a good vaccine response. Recovery with ofatumumab another anti-CD20 antibody in late stage development is much, much quicker because they use a low dose injected every week. This is not without potential issues.

However, is this going to be more vaccine ready and importantly what will this do to vaccinations?. The trial is ongoing NCT03650114 and it is involving 2010 people and guess what it was posted in 2018 with an end date of 2025, but the info says they actually started in 2010. So now is the time to crack the code…fear not it will be in the label even if it is not reported in a peer review paper ready for when the drug is approved. Will it give ofatumumab the edge….. I guess this approach is likely to give ocrelizumab a new patent as they are plugging the subcutaneous dosing hole (NCT03972306) with a trial testing 40-1200mg. They also did a trial to see if the infusion can be done quicker (NCT03085810). This is being review by the FDA. So it is all go on the B cell front. This will uncover biology.

However this may all be hypothetical. And could all be irrelevant.

Ocrelizumab does not impair B- and T-cell responses to primary VZV infection in a patient with MS. Novi G, Ivaldi F, Sbragia E, Mikulska M, Pesce G, Inglese M, Kerlero de Rosbo N, Uccelli A. Neurol Neuroimmunol Neuroinflamm. 2020 Feb 25;7(3). pii: e695.

This person developed chickenpox 3 months after the first round of ocrelizumab induced depletion. They developed antibodies to the infection. So it may occur for SAR-Cov2. We have to wait and see.

PET PEEVE….Now today is a holiday in the UK, and if you have your Union Flag out remember….PUT IT THE RIGHT WAY UP! THE WIDE WHITE BIT ON THE DIAGONAL IS BIGGEST AT THE THE TOP NEXT TO THE FLAG POLE….

It is amazing who gets it wrong. I remember the Association of British Universities got it wrong. That’s what happens when you have eyes on your flags, rather than a rope and toggle. I went to a meeting is a Dutch town and the flags there were upside down in a American Chain Hotel, I complained and they said it was a mistake, I then went to Streetview and showed them using the different years that it changed when Brexit arrived….Pathetic….Yes I am a pedantic.

If this Odd?

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MouseDoctor

23 comments

  • You lot are bonkers. Miss the NHS so much. ( Early ill health retired dietitian with ms).
    Love all the posts.
    Claire

  • Picture appreciation comment!

    Is Ocrevus one of Roche biggest blockbusters?
    Can’t imagine they’d want to do anything to hurt that

  • Interesting. In fact, years ago, some of the researchers across the pond in the US of A bemoaned the fact that RTX was shelved and OCR developed, in the first place, without much evidence of anything.

    Oblituximab and Ofatumumab are non-approved MAbs for MS. They are therefore not in contention from a patient perspective.

    • Ofatumumab will be here this year I suspect the trial data as it was reported end of last year. However, I have no idea maybe the Novarsians readers can comment on this. In the COVID era it is going to shake things up as you dont need to go to hospital to be infused and at least early on the B cells recover pretty quickly, this may be an attractive characteristic. However I suspect it is not that simple, especially if the dosing data with ocreliumab is correct in relation to progression.

      I suspect Ublituximab is in phase III UbLiTuximab In Multiple Sclerosis Treatment Effects due to finish in March 20201. I wonder what advantage it has, the infusion is abit quicker but Roche have finished therir more rapid infusion trial will struggle if it goes into phase III.

      I have heard of ofatumumab cancer variant being off-label used when people become immune to the humanised variant…However I will put money on this being withdrawn from the cancer market just like alemtuzumab was.

  • “We have predicted that you don’t need B cells and antibody to get (rid) of the virus …. If you have an intact immune response and viral immunity, nothing happens or the symptomatic problems are (blunted).”

    Can you elaborate on this? Can PwMS have immunity — full or partial — to covid-19 without B cells and antibodies?

  • Maybe it is my MS so I can’t really follow this kind of convoluted stream-of-consciousness technobabble.
    Too many typos don’t really help either…
    I normally really enjoy and appreciate the time and material covered in this Barts MS blog.

    As far as re-infection with Covid19 goes, some scientists have published papers showing that this is really just due to the way RT-PCR testing works. It amplifies dramatically the RNA fragments left over from genetic debris due to cellular and viral destruction. These people probably do not have active or infectious virus but they do have lots of old garbage from viral RNA floating around in their bodies for months post-infection.

    I don’t know if a drug company will do any testing or reveal the results unless compelled by law or regulatory necessity.

    All of the Covid19 serology antibody tests have limitations in their sensitivity and specificity.
    Very limited testing has been done on these due to the desire to streamline their introduction into clinical use. To date, NONE of these serology tests have been fully approved by the FDA for use in the USA. They have been granted Emergency Use Authorization after a very cursory review. There are dozens of different antibody tests proposed. Many have no FDA authorization. Some have better sensitivity. (Less false negative test). Some have better specificity (Less false positive test or positive to something that looks like SARS Cov2 antibody but is not). The accuracy numbers for these tests in a controlled lab environment by the inventors may be different from what is seen in a clinical and production test environment.

    I am hopeful and interested to see how people with MS respond to this Covid19 epidemic. Hopefully it is mostly good outcomes. It also would be good if the transparency or data relating to the effectivity of MS drugs in delaying MS progression as well as the associated underlying risks were revealed.

    • Sorry about the Typos….I have not had time to read them after posting.

      Thanks for your comments about the PCR. As for the comments about antibody testing I agree there are some labs that are testing the different tests.

      In UK Oxford tested the competition and said they were rubbish and then sold UK government 50 million tests made by Oxford….Dogey or what

    • It is possible to get at the primary data through sites like clinical trials data request.com. I’m in the ocrelizumab trial data right now.

  • Since you rarely post anything about it, I just have to try to ask randomly, off topic.

    I see that there are several ongoing trials testing socalled BTK inhibitors/ blockers. However, the actual data on efficacy seem to be hard to get a hold of.

    Can you explain:
    – what level of efficacy can be expected?
    – what the role of such medicines will be? Single treatment or add on? I remember prof G writing something about it being an add on maintenance therapy after an IRT e.g. Cladribine to reduce the “wait and watch” risk inherent in such medicines.
    – If so, will we have to wait another 10 years for it to be used as such?

    • There has been one study published by Merck and Montalban et al. a study was reported last month at the AAN by Sanofi-Genzyme. These are phase II and so we are some years away for these being available. The data should be as good or better than anti-CD20 but I have yet so see any evidence that they are as good. They stop early B cell development….however in MS the B cells have developed. How are they going to be used it is up to the companies how they get developed

  • Have you seen the video of Big Ian at the European ‘parliament’ complaining about the Union Jack being upside down?

    • The paisley I guess…I remeber that. It’s those cheap flag makers fault with the two rings there is no this way up with the old toggle and rope there was only one way to hang them

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