Hopebird

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The debate about what is active and inactive secondary progressive MS will not be settled by the EMA adopting a positive opinion, recommending the granting of a marketing authorisation for siponimod, which is now ‘licensed’ for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease. Siponimod reduces disability progression in people with active SPMS. The most common side effects are headache, hypertension and increased liver enzyme levels. The full indication is: “treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity (see section 5.1)”

This label will disappoint the many pwSPMS who don’t have active scans and therefore won’t be eligible for DMTs. I have commented on what is and is not active SPMS in the past. I think the siponimod label entrenches the MRIcentric worldview of what is active MS. We know that the majority of people dying with SPMS have ongoing inflammation in their brains and spinal cords at post-mortem. Try telling someone with SPMS who is getting worse that they don’t have active MS because they have no enhancing, or new or enlarging T2, lesions on MRI. And what about using CSF and/or peripheral blood neurofilament levels to assess activity? We clearly need to challenge the EMA’s and FDA’s definitions of what is active SPMS.

At least the licensing of siponimod for treating SPMS is a big positive for the field and indicates that we are beginning to address the unmet need in treating more advanced MS. 

The impact that this will have on our MS services should not be underestimated. We are now going to have to monitor our SPMS patients with annual MRI scans. Do we have the resources for this? What about the extra follow-up clinic slots? This alongside ocrelizumab for active PPMS is going to put a major strain on our MS services. Will our managers give us more resources?

Siponimod may not be an eagle, phoenix or maven, but rather a hopebird which symbolises the importance of “an optimistic approach to what lies ahead” and why it is important to have a “glass half full” attitude. Less than a decade ago we were telling our patients with a progressive course that they were beyond hope, that has now changed. 

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

26 comments

  • treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity (see section 5.1)”.

    Is this not saying that if you are having relapses you still qualify for treatment regardless of whether you have active MRI scans?

  • Prof G,

    Apologies for my thickness. I’m confused by the terms active and inactive SPMS. In old speak, inactive would be a good thing, but I’m guessing it isn’t really inactive but neurodegeneration – the dying off of brain cells. Does siponimod have no impact on inactive SPMS? Does inactive SPMS mean SELs and smouldering MS, or is this active SPMS? Sorry, for the Mickey Mouse questions, but the various terms are getting confusing for me eg Progressive and Advanced are bad things (but good when applied to non-MS things) and inactive is probably worse than active (as the latter can be treated)!

  • Why can’t Neurologists be given the freedom to treat MS in a “ belt & braces approach. I recall taking a friend fo an oncologist appointment, he commented, “ we treat with a belt and braces approach “. I get that Cancer can kill, but not all. I know people not treated in this approach and survived decades, only to die of something else. So why are the MS community so second rate in value, we have decreasing abilities and struggles as we age as you’ve discussed well on this blog. Surely, patients who have clearly progressed according to loss of ability should just be offered this opportunity. Not all will choose to take it. I’ve given up at 58, and likely SPMS, of being offered any new treatment but I hope so much the next generation of MSers are not given so many false hopes that I’ve witnessed over 2 decades.

  • “At least the licensing of siponimod for treating SPMS is a big positive for the field and indicates that we are beginning to address the unmet need in treating more advanced MS.”

    Surely you jest Dr. G.? “Big positive” for who? Progressive MS is not at all addressed with this or any immunosuppressive drug that is not CNS penetrant and does not address negative changes in innate immunity.

    Why is active SPMS not considered later stage RRMS?

    Would a patient that has activity in terms of relapses or Gd+MRI changes not qualify for a more efficacious medication like cladribine, ocrezulimab, alemtuzumab or HSCT?

    Why is this an improvement on fingolimod other than improved pricing for Pharma and their shareholders? Why is this innovative other than its marketing?

    According to FDA and EMA, this does not in any way, above placebo, address innate immunology/slow burn/PIRA. It targets deleterious peripheral immunity changes and in no way addresses the real MS, progressive MS.

    Lipstick on a pig is still a pig comes to mind. I cannot believe MS researchers just standby and watch this train wreck of MS research while patient’s lives are destroyed.

    • “…watch this train wreck of MS research while patient’s lives are destroyed.”

      Yes…it doesn’t register with them..just read these:

      “Progression is steady. Was on Ocrevus for 2.5 years. Progression continued during this time.”

      ” I seem to be in the same situation as you”

      “I am in same boat…Praying for all of us”

      • Annonie Mouse: Read my statement completely before you comment: CNS penetrant AND works on inhibiting innate immunity changes, which neither siponimod or fingolimod do. Purposely worded this way for a reason.

      • Another thing Annonie Mouse:

        EMA and FDA should not feel shame for refusing siponimod approval for non active MS patients. They are refreshingly telling the truth.

        Siponimod provided zero benefit over placebo to “non active” progressive MS patients. It simply does not work on progressive disease. It is just like any other immunosuppressant that works on the peripheral immune system, a downstream effect of MS.

        Dr. G. will argue it is not powered to look at non active SPMS patients. My question would be why did Pharma load a trial with “active “ SPMS patients when the largest unmet need is for “non active” progressive patients?

        Pharma preying once again on false hopes of SPMS patient for something/anything that impacts progressive disease when clearly it does not as proven by siponimod’s approval for only “active” SPMS by both the FDA and EMA.

        Also, “possible “ or “may” remyelinate is not a reality and are catch phrases thrown out by Pharma to prey on hope you once again. I heard the same garbage with fingolimod and copaxone. Where is the proof or publications or trials to prove these claims?

  • How ridiculous that getting treatment could be reliant on guidelines that insist on MRI scans. If I had waited for an MRI before I received treatment for my latest relapse I would be in a care home. This is why so many research trials are failing to help us. How many people with MS has had an scan in the past 20 years if they’ve not been on a DMT. I asked the question in October on this blog, as to how neurologists diagnosed relapses before MRI scanners, I didn’t get an answer. Now I realise the importance of my query, as it seems I would not qualify for Sipinimod as I didn’t have or need a machine to tell me or my Neurologist that I was having an MS attack. Let’s waste more NHS money on scans that are not necessary.

    • My point here is that the treatment availability is reliant on the scans and not examination by a qualified physician, therefore the trial lets us down. I’ve waited 6 months for scans and then the results haven’t been sent to my Neurologist. I’ve written to my MPs of different parties about various topics affecting pwMS. One went to see the Chief Executive of a major London teaching hospital. I have seen changes. So anyone in the UK that is unhappy, now is the time to either tell the politicians on the doorstep or write to them after the election.

  • I think it’s now dawning on the readers of this blog that (1)MS researchers haven’t got a clue about this disease And (2) the whole point about MS research is to expand and continue the MS research industry. I’ve had MS for 20 years and in that time it’s been 5 diseases (RRMS, SPMS, PPMS, RPMSand Benign) and is now 1. It was inflammatory and then neurodegenerative and is now neurodegenerative from the start. It’s been T cells then B cells. It’s been an escalation approach to treatment and then hit hard from the start. 4 different types of lesions were identified and now there is also the Slowly Expanding Lesion. The disease is active and inactive! There is the Black Swan and now the Hopebird. The researchers have promised the earth (remyelination, neuro-protection, neuro-restoration) and not delivered. Everytime a new anti-inflammatory is licensed, problems appear a few years down the line (PML, thyroid problems..). We are talked down to like kids and told off for being glass half empty rather than glass half full people. Go to my local MS Society meeting and you would be a glass empty person. I don’t want to be in an electric wheelchair at 52. I don’t want to be in a care home at 55. What do the researchers and neuros not understand? I’m not going to be grateful for a treatment that allows me to continue to brush my own teeth for another 4.6 months! If you turn up at your neuro on Monday morning with PPMS or SPMS there is nothing your neuro can give you in the U.K. ie nothing that stops the relentless progression. Thank god everyday Prof G that you don’t have MS – you wouldn’t be the glass half full person you are today.

    Okay – rant over. Have a good weekend. But the points I make are real. As a patient, the treatments available to treat this disease (not relapses or focal inflammation) are pitiful. If you think they are available Prof G, then I’ll send you my address and you can pop the pills in the post.

    • The points you make are real. As a medical science researcher (not MS) with MS I guess I can see both sides of the story, and I don’t want to be in a wheelchair or a care home in the near future either.
      The average time for the discover of a drug to clinical approval is 12+ years… and that’s for diseases that are fully understood.
      MS is a relative small population, therefore many side effects e.g. thyroid etc don’t show up until after a drug is licensed, is it better not to have the drug licences at all??
      The team at Barts and many others around the world are doing the best that they possibly can given funding, government approval and many other factors that seem to be insurmountable obstacles.
      In my opinion, no one here talks down to pwms, in fact just the opposite, everyone is really trying to be inclusive of pwms. The way the researchers try to include pwms should be held up as the gold standard for how to include patients.
      If you think that the first MS drugs only became available about 25-ish years ago, the field has actually come a long way in a short time, especially in the last 10-12 years.
      I really do know it’s hard and frustrating it is to be a pwms, but I also know how hard it is to be a med sci researcher.
      I know how good it can be to vent occasionally but there are always 2 sides to every story.

        • But compared to some cancers, cardiovascular disease and diabetes to name a few, it is still small. Then cut that population down for the clinical trials due to age, EDSS, use of previous treatments, other comorbidities, the cost of trials, and the fact that trials by their nature run for a finite time, then it is not surprising that many side-effects only appear in post-marketing surveillance.

          • I find it valuable to have your view as a medical science researcher, especially as it can be so easy to feel desperate as a PwMS. In my view the fact that you can bring both to the table adds to the legitimacy of your views and insight.
            I try and remind myself that MS is the only neurological condition for which any treatments are available. But I do wish that the treatments were available to everyone diagnosed everywhere: here in the UK and elsewhere.
            I also agree that here everyone with MS, even those who’s comments are so scathing , even unpleasant, are treated with respect and are not patronised. I’ve experienced more than once clinicians being alienated, I’d even say threatened, by my being a well informed PwMS with no medical or scientific background. So yes, this site is most definitely gold-standard!

  • Hi everybody,

    Excuse me if this has already been covered and my lack of understanding , if relapsing remitting SPMS is something in between RRMS and SPMS , why do you need to use siponimod ? it is going to maybe stop relapses like any other drug but it is going to do nothing to stop SPMS? Is siponimod p great breakthrough ? I do not believe that . Why would you give this drug and not any other drug that effectively stops relapses ?

    Nothing stops SPMS unfortunately , why is it so misleading and creates so much confusion all this advertisement? Please just stop confusing .

    • Although we can’t stop SPMS getting worse we can slow it down. This is what these treatments do, which is why we have to manage expectations.

      • Thank you very much Professor g for your answer . It is very difficult for an SPMS patient to know how bad it would’ve been without the medication . Because things are not stopped you never know how fast you are deteriorating …. it is very easy to get frustrated and lose hope .

  • Let’s see…we’ve had the “Black Swan” and now the “Hope Bird”. Is there an open season for these birds? They’re annoying as h***.✌️Out.

  • If an SPMS who is denied DMTs goes to a compound pharmacy and gets DMF, how different benefits would he/she have comparing to receiving Siponimod, do you think? The same difference Fingo has to DMF I guess (generic leflunomide might be a better option though, as we know that teriflunomide has better results on brain atrophy).
    The innovation is poor, the idea of treating SPMS is valid though.

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