The tortoise has finally arrived

T

The FDA has just approved ofatumumab for patients with relapsing MS.

See Novartis’ press release below.

  • Ofatumumab delivers powerful efficacy with a favorable safety profile and can be self-administered at home, addressing significant unmet needs for people living with relapsing forms of multiple sclerosis (RMS)1
     
  • Approval based on two Phase III ASCLEPIOS studies demonstrating significant reductions in risk of relapses, confirmed disability progression, Gd+ T1 brain lesions and new/enlarging T2 lesions1
     
  • Ofatumumab may halt new disease activity in RMS patients as shown in a post hoc analysis, with 47.0% and 87.8% of patients treated with ofatumumab achieving no evidence of disease activity (NEDA-3) within the first (0–12 months) and second year (12–24 months) of treatment, respectively2

Due to Novartis’ recent bribery case in the USA they are going to have trouble marketing and promoting this product in the US, which means the anti-CD20 marketing wars are going to be asymmetric.

“For more than a decade, Novartis spent hundreds of millions of dollars on so-called speaker programs, including speaking fees, exorbitant meals and top-shelf alcohol that were nothing more than bribes to get doctors across the country to prescribe Novartis’ drugs,” said acting US Attorney Audrey Strauss for the Southern District of New York.

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27 comments

      • Dont worry the immunologists will do this, but not all cells found in Harvard goes anywhere….The Th17…does the X cell mafia say this is all now crap what happened to the Th3?

  • Only subcutaneous….I suspect not for long Roche have been trialing subcutaneous ocrelizumab since 2016
    NCT03972306.
    Will oftumumab get a COVID boost….Interesting that the phase III trial data did not report neutralizing antibodies….it is a matter of time for a few individuals just because it is human does not mean the preparation is not immunogenic…..DrAngry put the kettle on and take a breather as….you’ve got another to do.

    • Did they just not test for neutralizing anti-bodies, or did they tested for them and find that no one developed them? Either way, I agree, it is only a matter of time.

      While rare, it does happen (as with my experience while on Ocrevus). So please, please, please put out a commercially available anti-drug antibody test. I do not want any other pwms to go through what I did!! If funding is problem, I am sure the many readers of this blog would be happy to support a “go fund me” campaign. Information is currency, and results in more honest discussions about the risk/reward balance of selecting a DMT.

    • Only self-adminsitered B cell….not exactly true. Cladribine tablets are self administered and it is an anti-B cell therapy….in fact they are all anti-B cells but some better than others.

  • Prof G put up a post a week or so ago and noted that:

    “I think anti-CD20 therapies are lulling us into a false sense of security, i.e. because anti-CD20 therapies are so good at suppressing relapses and focal MRI activity we think we have sorted out the treatment of MS. However, when you look carefully at the end-organ of pwMS on anti-CD20 it is clear that their brains are still being shredded by smouldering MS. It is clear to me that we need to go way and beyond ofatumumab and anti-CD20 therapies to target whatever is causing smouldering MS.”

    Can anyone on Team G tell me what add-on/s are required e.g anti-viral, a different type of anti-inflammatory…. Also, is any such add on in trial or near to trial? We seem to have come on leaps and bounds in addressing focal inflammation and relapses, but are yet to make any real in roads in addressing smouldering MS (which I understand equates to progressive disability / end organ damage). Give us some hope MDs.

    • Now with several anti cd20 that will put an end to relapses we will start having much more young PMSers. Then or the landscape will change recognizing the real smouldering MS or people will be treated as PMS that will become the only MS left in the world affecting everyone with MS.
      At that point pharma will have anyway to aim for a single target (degeneration) for all types of MS.
      In the end, smouldering MS will be addressed anyway as a consequence of anti cd20.

        • Maybe I am missing something… I haven’t seen trials on combinations. Are you referring to BTK inhibitors in the combo or you know something more, ProfG?

        • Are there any that are showing any promise Prof G? I have read the upcoming metformin trials but what else is in the pipeline? I guess like a lot of other CD20s who are reading this blog, we are just looking for some hope

    • There’s trail ongoing thats comparing Stem cells versus Dmt alemtuzumab, ocrelizumab, etc. This will finally put to rest this on going debate is MS a B cell mediated disease or not. My money is on X cells.

    • We were doing this years ago…what add-ons…we gave you the pyramid…it is not our gift to offer. The MDs have been saying what needs to be done for years…you have to get the neuros to change their behaviour and do combinations…whilst pharma control the show that is some way off.

      • The pyramid was just a fancy graphic. We never got off first base – anti-inflammatories. The Mouse Doctors are the the real chuckle brothers of the MS research world passing the blame to the neuros or to pharma. We need a Nuremberg type trial for all those who have been involved in MS research to find out why after 50 years we have made little progress in addressing the real MS. The little Mouse Doctors will claim that “we were just taking orders from our superiors”….. “nobody listened to us”.

        As Mussolini said “It is better to live one day as a lion than 100 years as a sheep.” I’m afraid to say that the MDs have taken the sheep option. Pushed around by neuros and pharma.

        • That’ll be the Mussolini whose tanks had 5 gears, all reverse? 😉
          There are many MS scientists worthy of your scorn, we are very proud of our record.
          Have a lovely weekend, Sid, (I’ve just dropped another kilo) 🙁

  • Hi MDs, for the layperson, what is the difference between Ofatumumab & Ocrelizumab? If they both do the same job, is it just pharma competition – if so, surely as you’ve all confirmed in the past, why are they making another CD20 drug that helps certain types of pwMS but not really tackling the ‘elephant in the room’ degeneration! For me ‘T,’ ‘B,’ or ‘X’ cells – I would just like to know that, if we are going to be taking these awful medications and to prolong our lives without further disability and or cognitive decline, we should definitely be looking at a cure and finding a better drug to combat inflammation.

    • Here here. My point exactly. People are so caught up about B and T cells, and whose right and wrong, but neither therapies cure. Ok Alemtuzumab and HSTC make the immune forget to attack the myelin. But i bet in sufficient time, sufficient people will redevelop ms.

      • The name tell you what they are and what they were designed for. Monoclonal antibodies (MAB) were historically made in mice or rats. They inject mice with human proteins and they make an antibody response against the human protein. However mouse immunoglobulin proteins that make up the antibody cause an immune response and are rapidly rejected and so you try an limit the rejection (immunogenicity). There are chimic (XI) antibodies where the antigen-binding fragment antibody comes from the originating mouse monoclonal antibody, but to make it less immunogenic they have replace most of the mouse bits with human antibody (immunoglobulin). You can reduce immunogenicity further by making the antibody humanised (ZU) so only the bits contacting the target are mouse derived. The next stage is human (MU) where often the have made a mouse that had human immunoglubulin genes and so make human proteins. These antibodies were originally made to target cancer (TU) or sometimes the immune system (LI).

        So you have riTUXIMAB (chimeric antibody) that causes anti-drug antibodies in about 15-25% of people within a few years. This is infused into the blood every 6 months. It’s patent was running out so ocreLIZUMAB (humanised antibody) was made. This is injected (infused) every 6 months also but it only causes ADA in less than 1% of people. This may be because it is humanised but also th dose makes a dfference so if you drop the dose from 600mg to 20mg the frequency of ADA goes up. OfaTUMUMAB is human and was made for cancer as an infusion, but development was halted in multiple sclerosis so that it could be given at a lower dose (60mg) and injected under the skin every month. It allows the B cells to return quicker and you don’t need to go to hospital to have it.

        They may have different prices and approvals.

        There is another anti-CD20 (B cell ) depleting antibody comming for MS, Ubliximab (this is chimeric but it has been engineered to have a higher ptenecy than rituximab.

        However, there are many may more variants available

      • The reason why it is important to understand what is the problem is that allows you to monitor things and allows you to make it better and reduce side effects

    • Ocrelizumab is administered in a hospital and healthcare system has to pay for the treatment to be given to people plus the cost of the drug.
      Ofatumumab can be administered at home so, if the price is the same, the latter is cheaper because you do not need to set up hospitals to do infusions.
      There are people not comfortable with going to hospital even if it is just twice a year.
      With pandemic like covid people can get cd20 drug at home without exposure to risk of infections with better treatment adherence and possibly outcome.
      Then Ofatumumab is fully human and it should be, in theory, less immunogenic.
      In the end it is competition and as already posted in this blog pharma hunts in pack and they do similar drugs. but sometimes equivalent drugs have different pro and cons.

    • The name tell you what they are and what they were designed for. Monoclonal antibodies (MAB) were historically made in mice or rats. They inject mice with human proteins and they make an antibody response against the human protein. However mouse immunoglobulin proteins that make up the antibody cause an immune response and are rapidly rejected and so you try an limit the rejection (immunogenicity). There are chimic (XI) antibodies where the antigen-binding fragment antibody comes from the originating mouse monoclonal antibody, but to make it less immunogenic they have replace most of the mouse bits with human antibody (immunoglobulin). You can reduce immunogenicity further by making the antibody humanised (ZU) so only the bits contacting the target are mouse derived. The next stage is human (MU) where often the have made a mouse that had human immunoglubulin genes and so make human proteins. These antibodies were originally made to target cancer (TU) or sometimes the immune system (LI).

      So you have riTUXIMAB (chimeric antibody) that causes anti-drug antibodies in about 15-25% of people within a few years. This is infused into the blood every 6 months. It’s patent was running out so ocreLIZUMAB (humanised antibody) was made. This is injected (infused) every 6 months also but it only causes ADA in less than 1% of people. This may be because it is humanised but also th dose makes a dfference so if you drop the dose from 600mg to 20mg the frequency of ADA goes up. OfaTUMUMAB is human and was made for cancer as an infusion, but development was halted in multiple sclerosis so that it could be given at a lower dose (60mg) and injected under the skin every month. It allows the B cells to return quicker and you don’t need to go to hospital to have it.

      They may have different prices and approvals.

      There is another anti-CD20 (B cell ) depleting antibody comming for MS, Ubliximab (this is chimeric but it has been engineered to have a higher ptenecy than rituximab.

      However, there are many may more variants available

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