Today the EU licensed siponimod for the treatment of active secondary progressive MS. It has been a very long and winding road to get here.
Siponimod is not an eagle, phoenix or maven, but rather a hopebird which symbolises the importance of “an optimistic approach to what lies ahead”. Less than a decade ago we were telling our patients with a progressive course that they were beyond hope, that has now changed.
Being able to offer treatment to people with SPMS will be a challenge to the NHS, because of the way our services are configured, but it is doable. If there is a will to make it happen it will happen.
The next task is to challenge the term ‘active’ SPMS. What does it really mean? How can you tell someone with worsening SPMS they don’t have active SPMS. I think it is time to challenge the old dogmas that thave crept into our field. I also hope siponimod will be a segway into a new era of combination therapy.
CoI: multiple; in particular, I sit on the Siponimod SPMS trial steering committee
I just read your article about Siponomod, I must say it made me very emotional, it’s been a long time coming, and let’s not forget to thank you Gavin who introduced me to this life changing drug X😇
Prof G,
“I also hope siponimod will be a segway into a new era of combination therapy.”
The idea of combination therapy has been around since I was diagnosed with RRMS 13 years ago, but never gets beyond the navel gazing stage. What therapy would you add to a drug like Lemtrada to achieve combination therapy? What would the add on therapy be seeking to achieve? Are there any therapies already available to act as an add on therapy?
Any idea of when a combination therapy will be available? I’m assuming trials are needed so looking at 10-15 years time.
Good luck with all your research efforts.
How do the figures for siponimod compare to your experience with cladribine?
I know there are no direct comparisons but what is your gut feel?
Not sure we only use cladribine in highly-active relapsing patients.
I meant when you have used it for those in wheelchairs IV off label Who who are obviously progressive
We can’t compare; as siponimod has not been trialled in wheelchair users. EDSS range in the EXPAND trial was 3.0-6.5 ;-(
How does fingolimod compare to cladribine in rrms and do those results give you a gut feel for how siponimod and cladribine would work when used in in wheelchair users?
All is revealed in today’s post by NDG. Cladribine is not only cheaper but more effective in RRMS.
This is not optimism. Mayzent/siponimod is false hope masquerading as a meaningful treatment in progressive MS to cash in on the hopes of unsuspecting progressive patients. If one takes away this selection bias trial’s “active” SPMS or end-stage RRMS patients then you have zero effect above placebo on progressive MS.
The FDA, EMA , Health Canada have approved for only “active” SPMS not the majority of SPMS patients, non active SPMS.
This is not an unmet need or a meaningful treatment for progressive MS as proven by the approving bodies denial for approval for treatment of all SPMS patients.
Why is siponimod better than fingolimod, or any other immunosuppressant that has an effect on adaptive peripheral immunity? Why is active SPMS any different than later stage RRMS?
How does siponimod dampen or inhibit the deleterious changes in innate immunity? Simply put it does not as it has no effect above placebo using their data in “non-active” SPMS patients.
History will not be kind to those involved in this era of immunosuppressant only for massive profits to all those involved for “possibly” a slight decline in deterioration but to the same miserable endpoint.
In this case, siponimod by Novartis offers at best, with a loaded trial full of “active” SPMS patients or one could argue RRMS patients, a chance of less worsening above taking nothing by a paltry 23%.
Lipstick on a pig. is still a pig!
Unfortunately I couldn’t agree with you more.
Prof G posted an article on his twitter account that of all the medical specialisms, neurologists are the unhappiest out of work:
https://mobile.twitter.com/GavinGiovannoni/status/1218280085574311937/photo/1
This doesn’t surprise me at all. Everyday they send patients home with a diagnosis akin to a death sentence – MND, Parkinson’s, PPMS, Huntington’s Chorea ….. 7 years of study, a PhD, years of research and on the job experience and none of these patients gets better. I have no doubt brain diseases are up there with the most complex disease, but as cancer treatments and treatments for non-neurological diseases leap forward we are thrown scraps of hope.
As you say, Siponimod isn’t addressing the real MS, isn’t stopping progression in its tracks. I have sympathy with neuros and MSologists, but they have been stuck in a rut for the last 25 years following the licensing of the first treatments. There is too much money involved and too many reputations at stake to rock the boat. But as MS patients we shouldn’t be lulled by the claim that there are treatments for progressive MS. We need some honesty. A treatment that stops increasing disability is a real treatment for progressive MS. With stability we can plan again, look forward to the future etc. Slowing deterioration down by a few months or pushing back the need for a wheelchair by a year is the worse of all worlds. It just lengthens the suffering and the number of days we wake up with these wretched disease. It’s time for real advances to address the real disease. Researchers have had a good inninings with MS but now need to put it to bed and. I’ve on to the other dreadful diseases that fall under the neurology specialism.
Agree 100% Ken.
Novartis (Pharma) and it’s paid neurologists, researchers and statisticians are “gaslighting” the progressive MS patients for profits into thinking they have a meaningful treatment for progressive MS, when they clearly do not.
Hopebird is singing? More like Hopebird has been shot and has uttered it’s last breath as it falls from the tree.
Get a room guys 🙂
Here comes a practical question: A long term patient on high efficacy maintenance therapy (10 ys +) is relapse free but showing signs of smouldering MS on low res (1.5 Tesla) standard MRI scan.
When are they deemed to have switcjed to SPMS in the absence of relapses?
And if the answer to the question is complicated, why not consider flipping that patient to siponimod pro-actively in anticipation of full blown SPMS?
Those questions assume that immune reconstitution can be controlled during the transition.
Tony
Re: ” … consider flipping that patient to siponimod pro-actively in anticipation of full-blown SPMS?”
As they don’t have active SPMS, i.e relapse and or recent focal MRI activity, you won’t be able to. Siponimod is only licensed for active SPMS.
There is a vast number of people who have has MS for many years and are now diagnosed with SPMS but it is not active. This includes people who are pre DMT. What real hope is there for these people?
CoI – i am one of these people with no hope
Agreed, by the terms of the license, the patients Tony described are not eligible for siponimod.
I think his question may have been hypothetical: would it help the smouldering MS if they could get siponimod? Is that something worth aiming for?
Speaking as someone with what appears to be inactive PPMS, this is nothing like a “hopebird” but just another old battery hen.
I agree siponimod is fingolimod under a different name retargeted at a different audience in order to make money after the patent for fingolimod expired last year.
However at least they have a treatment for spms
Prof g would you expect most DMT if trialled for spms to be effective to some degree especially as you believe Ms is one disease,?
Unfortunately pharma have now realised that failed clinical trials waste a lot of money. In their never ending greed they now front load trials with people likely to respond. Then they skew the data to show positive outcomes. Prime example Biogens alzhmiers treatment. And with enough sweeteners they known they can get approval from fda and ema. Example biogen with the all clever people in the world and mathematical tools missed positive responders. Just like in the failed Anti lingo trial. Sounds familiar? Don’t worr, there will be more examples to come. It’s not enough pharma stifle any efforts to find a cure. Now in order to recoup lost investment will push ineffective treatments. Sponimod is no more effective then fingolimod but with less side effects. Which failed in progressive. Sorry barts this article is more to make pharma happy.
Could it be the FDA are giving the sweetners, most pharma have dumped Alzheimers and maybe the FDA have realised it is better to throw pharma a bone so they come back for more, otherwise there is nothing.
Yes. I’m not stating facts just opinions. From the information I see and know it seems that way. The problem is the huge cost of trials and the length of time they take. To reduce the cost of trials. They should be limited to 3 years in length. The numbers should be limited to the median point between phase 2 and 3. This eliminates the need for 3 phases. Also there should be multi end points. Eliminate placebo double blinded where treatments already exist and compare with highest efficacy treatment., No mimick like ozanimod, posinmod, fingolimod, etc. Where is the flaw in this sensible approach?