Saturday, 28 May 2011

How long does it take to develop a DMT?

The following is fingolimod's time-line. This is typical example how long it takes to develop a DMT for MS. If the PPMS trial is positive fingolimod will only be available for people with PPMS in late 2014 or early 2015.


"Is it fair to make people with PPMS wait this long?"


  1. 1992: Fingolimod (FTY720) first synthesized by Japanese scientists
  2. 1997: Fingolimod in-licensed by Novartis for clinical development
  3. 1998: First studies in man (Phase 1 trials) and subsequent start of transplantation trials
  4. 2003: Start of MS Phase II trial
  5. June 2005: Presentation of Phase II study results followed by publication in NEJM 2006
  6. Jan 2006: Start of Phase III FREEDOMS study in RRMS
  7. May 2006: Start of Phase III TRANSFORMS study in RRMS
  8. June 2006: Start of Phase III FREEDOMS II study in RRMS
  9. July 2008: Start of Phase III INFORMS trial to assess suitability for treatment of PPMS
  10. Dec 2008: Release of TRANSFORMS study results and presentation at AAN April 2009
  11. Sep 2009: Release of FREEDOMS study results and presentation at AAN April 2010
  12. Dec 2009: Regulatory submission to FDA and EMA (ROW submissions in Q1 2010)
  13. Feb 2010: Results of Phase III TRANSFORMS & FREEDOMS studies published in NEJM
  14. Sep  2010: Approval by Russian Health Authority
  15. Sep 2010: Approval  by the US FDA for relapsing MS
  16. Jan 2011: Approval by the European Medicines Agency for highly-active relapsing MS
  17. April 2011: Licensing approval in the UK for highly-active relapsing MS
CoI: I have received personal compensation from Novartis for being a member of the phase 4 fingolimod development programme and our centre is one of the sites participating in the phase 3 PPMS trial. 

7 comments:

  1. "Is it fair to make people with PPMS wait this long?"

    NO

    Given that the focus has been on the inflammatory phase and there are now potentially very effective treatments coming on to the market, the focus must shift to treatments for progressive MS. Safety really isn't such an issue if you are progressing quickly. If there are potentially promising agents - these can be tested in the usual Phase i - iii trails, but they could also be issued to patients now (who would be happy to take them if there was a chance of stopping / slowing the progression). We've got to think of ways of giving patients an option to have treatments which should hypothetically work, but haven't been formally tested. Neuros really need to think how they would feel if they were in the progessive phase of MS - loss of independence, dignity, work etc. If there was an agent which potentially showed promise but had yet to go through 5-7 years of testing, would they want an opportunity to take it.

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  2. Goodness me, it took Robbie Williams less time to come back to Take That than what it’s taken scientists to figure out that Fingolimod might stand a chance at benefiting PPMS sufferers.

    On a serious note, you seem to advocate the use of Fingolimod in PPMS because it has an impact on slowing down brain atrophy in RRMS therefore it has more than a fair chance of being effective in PPMS. Does this mean that a neurologist would have to prescribe it off-license? Cannot my GP prescribe it off-licence? Where can one find an intrepid enough clinician who will provide Fingolimod to me? If there is such a belief in the treatment powers of Fingolimod in PPMS then why is there not greater faith in prescribing it to PPMS sufferers, in general?

    To be honest it is not fair to keep PPMS patients waiting for another 5 years to conclude the efficacy of Fingolimod; not if it can help us now. This is a drug that already exists. It’s on the market. It’s powerful, some might argue too powerful. So far nothing that ostensibly benefits RRMS patients has shown to help PPMS sufferers. Perhaps at the moment PPMS patients are beyond hope, but that doesn’t make it any easier. Rather than hearing terrible stories about people flying out to Rotterdam or Costa Rica for ineffective (bovine) stem cells which they only do out of fear and despair, perhaps neurologists need to engage in immediate and individualist thought of how to offer something that may truly help PPMS patients right now. Yes the expectations of PPMS sufferers might be too grand, but I have read enough about potential neuroloprotective compounds that already exist but there’s no effective plan of action to get these drugs to PPMS patients in the fastest time possible. That’s not fair.

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  3. By the way, you said that that hand transplant worked because the hands are already made and only need connecting, well my Central Nervous System is already made... I guess that it just lacks myelin and is need of a bit of nerve fibre is all. (I bet you’re shaking your head thinking if only it was that simple anonymous commentator... who knows, maybe it’s simpler that what is imagined...)

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  4. I'd just like some sense of when (if) there might be an effective / partially effective treatments for progressive MS. EDSS 8 was the point I decided I'd have had enough. Living with the unpredictability of this disease is hard enough, but not having any sense if anything will be available in 5,7 10 years make it much, much harder. So many initiatives e.g. tissue bank, but cracking progressive MS (understanding the mechanisms and coming up with treatments) seems to be too much for even the best of our researchers. We put a man on the moon 40 years ago, but cannot figure out what's going on in brain tissue under a microscope. I don't doubt the immense effort being made by Prof G and others, but it's so frustrating that the cause / mechanisms causing the damage are still an unknown.

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  5. I have PPMS and I’m young – much younger that what most people who get this form of the disease are. Other than mobility problems, I’m in great shape and (minus my PPMS) otherwise in good health. Neuros should be more willing to give me a drug like Fingolimod because I reckon my body, on account of its moderate youth, will be able to handle it even if it doesn’t benefit me in the way I hope it will. If it doesn’t kill me then it can only make me stronger. Saying that, it would be good if it actually did benefit me because it burns me up to see RRMS patients my age at our local MS centre gloating about how much they’ve benefitted from taking something like Tysabri while I’m out in the wilderness simply decaying from this disease called PPMS.

    I honestly hope that Anti-Lingo-1 really works. I hope that it speeds through the trials phase with splendid results. The timeline given above sucks, it really does. I’m so disappointed at the current state of the PPMS drugs market that I’m already bracing myself for the Anti-Lingo-1 trials to fall apart and another potential drug biting the dust. I must come across as so jaded but can you blame me (or any of us PPMS patients for that matter). Like the person above said, our nervous systems have the oligodendrocyte cells needed to make new myelin so why the delay? Fingolimod sounds good but there’s no chance of it producing remyelination in PPMS patients because the pathology is different; our olygodendrocytes are dormant unlike those with RRMS. In order for us to remyelinate the oligodendrocyte cells need kick-starting. Still, it’d be nice to stop or even slow the progression.

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  6. "On a per head basis, MS is the second most expensive neurological disease on the planet... Brain tumours are the most expensive but the next one in is multiple sclerosis, far above stroke, Alzheimer’s, Parkinson’s, etc. Now, those are the real costs to society - the costs not only of your treatments but the costs of people having to take time off work and all of the various knock on costs. This is a figure that I think should be burnt into the brains of people who make decisions about health policy. The total EU cost of MS in any one year is 9 billion, not million but billion, Euros. That’s a huge amount of money. As we’re talking about such vast sums of money here I think it’s really important that the MS community gets across to the policy makers and the people who decide how to spend budgets just how important a disease this is and just how great the societal cost actually is." Charles ffrench-Constant - MS Society Edinburgh University Translational Research Centre

    MS is a disease that needs to be prioritised. Rather than wasting money on just care and services, the government needs to invest more in research. MS is predominantly a young persons' disease. These people are in the prime of their lives with more years ahead of them than behind them. The costs of not developing medicines to stop progression and reverse damage will only add pressure on national finances. It makes no sense why this issue is not argued in Parliament. We don't just need a cure/ treatment for the patient's sake; it’s society that will ultimately benefit most of all. MS is not just a drain on the sufferer; it's a drain on social pockets. We need less deliberation and more action.

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  7. Cost-effectiveness assessments or rationing of health care is a very difficult area. I agree that we need to take into account both direct (NHS) and indirect (societal) costs when making a call. This is something we need to lobby the government and the relevant stakeholders to do. As far as spending more money on research; I would say yes, but then I would say yes as I have a vested interest in research. Not all research is productive so we need to adopt methods that try and increase research prductivity (output, quality and clinical relevance). For example, (1) priming blue sky research by funding individuals with a track record in creativity, (2) allocating resources at targeted problems, (3) making sure that well-defined programmes are milestone driven, and (4) funding infrastructure to underpin research (biobanks, registers, etc.). At the end of the day it is tax payers money that is funding research we therefore need to demonstrate value for money.

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