#MSBlog: NMSS Promise 2010: Did we break our promises?
“I am about to leave Los Angeles. As promised I have uploaded my slides from last night’s talk.”
“I spoke at the Southern California Chapter of the NMSS annual golden circle fund raising dinner last night. I last did this in 2008 and saw some familiar faces in the audience. I was particularly impressed by hearing that this chapter raised over $3M for the Promise 2010 initiative. Well done!”
“I also had the opportunity to touch base with the wonderful staff of the Southern Californian Chapter – appreciative, friendly, hospitable, hard-working and simply great hosts. I shared the platform with Cyndi Zagieboylo, the NMSS’s CEO; a very impressive lady with vision and lots of experience in the field. She was also sporting a very cool haircut, as one observer put it, but that is another, very inspirational, story! The NMSS are very fortunate to have her.”
“I challenged the audience to judge whether or not we have broken our promises! Some readers of this blog clearly think we have not delivered on the promise.”
“I tried to structure the talk around the four aims of our research programme, presenting a narrative around each aim. In preparing the talk I realise, with some pride, that we have delivered on all of our aims, to a greater or lesser extent. The fact that we have 3 follow-on phase two clinical studies addressing neuroprotection in MS and three follow-on basic science grants is testament to the success of our programme. However, we have yet to deliver a treatment for progressive MSers, which is why some MSers think we have failed them. I think the latter is more to do with unrealistic expectations. We never once said in our application or in discussions with MSers and the NMSS that we would have a treatment for progressive MS after only 5 years. This is far too short a time to deliver a treatment. I therefore used the development programme of fingolimod to illustrate the point that it takes decades to develop treatments. For example, it took 18 years from the time the fingolimod molecule was discovered to it becoming licensed as a treatment for MS. Innovations entering clinical practice today started in the laboratory 15-20 years ago. The simple reality of scientific progress is that it takes a relatively long time to deliver tangible benefits for people with disease.”
“At the end of the talk I presented the headline results of Dr Jeremy Chataway and colleagues Simvastatin SPMS trial and the problem we will face getting funding for the required phase 3 studies and the hurdles getting the drug, and related drugs, licensed for MS as they are now off patent. I also had some discussion after the talk about how the current system does not support the repurposing of off-patent drugs. If we could solve this problem we would definitely be able to accelerate drug development for progressive MSers.
“Dr Chataway’s simvastatin trial definitely comes a close second on my 2012 highlights list for MS after the publication of the phase 3 alemtuzumab results and the alemtuzumab submissions to the EMA and FDA.”
“I am about to leave Los Angeles. As promised I have uploaded my slides from last night’s talk.”
“I spoke at the Southern California Chapter of the NMSS annual golden circle fund raising dinner last night. I last did this in 2008 and saw some familiar faces in the audience. I was particularly impressed by hearing that this chapter raised over $3M for the Promise 2010 initiative. Well done!”
“I also had the opportunity to touch base with the wonderful staff of the Southern Californian Chapter – appreciative, friendly, hospitable, hard-working and simply great hosts. I shared the platform with Cyndi Zagieboylo, the NMSS’s CEO; a very impressive lady with vision and lots of experience in the field. She was also sporting a very cool haircut, as one observer put it, but that is another, very inspirational, story! The NMSS are very fortunate to have her.”
“I challenged the audience to judge whether or not we have broken our promises! Some readers of this blog clearly think we have not delivered on the promise.”
“I tried to structure the talk around the four aims of our research programme, presenting a narrative around each aim. In preparing the talk I realise, with some pride, that we have delivered on all of our aims, to a greater or lesser extent. The fact that we have 3 follow-on phase two clinical studies addressing neuroprotection in MS and three follow-on basic science grants is testament to the success of our programme. However, we have yet to deliver a treatment for progressive MSers, which is why some MSers think we have failed them. I think the latter is more to do with unrealistic expectations. We never once said in our application or in discussions with MSers and the NMSS that we would have a treatment for progressive MS after only 5 years. This is far too short a time to deliver a treatment. I therefore used the development programme of fingolimod to illustrate the point that it takes decades to develop treatments. For example, it took 18 years from the time the fingolimod molecule was discovered to it becoming licensed as a treatment for MS. Innovations entering clinical practice today started in the laboratory 15-20 years ago. The simple reality of scientific progress is that it takes a relatively long time to deliver tangible benefits for people with disease.”
“At the end of the talk I presented the headline results of Dr Jeremy Chataway and colleagues Simvastatin SPMS trial and the problem we will face getting funding for the required phase 3 studies and the hurdles getting the drug, and related drugs, licensed for MS as they are now off patent. I also had some discussion after the talk about how the current system does not support the repurposing of off-patent drugs. If we could solve this problem we would definitely be able to accelerate drug development for progressive MSers.
“Dr Chataway’s simvastatin trial definitely comes a close second on my 2012 highlights list for MS after the publication of the phase 3 alemtuzumab results and the alemtuzumab submissions to the EMA and FDA.”
Then please give us a realistic time frame for when treatments for progressive MS may come about… no wait, they will only get changed again because they either won't work out or you'll plead for more time.Prof G, we realise you're trying to advance treatments for PPMS but the lack of clear dates is frustrating. We have waited lifetimes for something and it seems we may have to wait for much longer. PPMS is a harsh disease course and it seems forgotten. We hardly read posts about PPMS in specific which makes me wonder if enough researchers and pharmas are interested in it.
Prof G,This is where researchers and MSers are miles apart. I remember the launch of Promise 2010, way back in 2004. One of the promises was "Nervous System Repair and Protection" – "repairing damage and restoring lost function". These weren't the words of MSers, but the NMSS (advised by MS researchers). I see not success on this front at all – so a broken promise.Even if we look at neuro-protection, there are no treatments available. The researchers are trailing existing drugs knowing they won't get licensed! As above, I would like a timeframe of when neuro-protective treatments will be accessible to MSers – 5, 10, 15 years? What about the promise of restoring lost function? This was the hook which sucked me in and led to me donating. In any other walk of life this would be fraud! Until treatments are readily available, Promise 2010 has been one big failure – at least for MSers.
Promise 2010. You are asking us to justify what we did but also what the other three consortium did. We can not answer for them and their goals were much more focussed on repair. Maybe we could ask for a post. However I hear many of you extol the virtues of Franklin lab. This was part of the ffrecnh-Constant consortium and this has delivered targets for repair. I do nto believe they were funded under that funding round to do a trial on what they found. It seems an unrealisitic expectation"They are trialling exisiting drugs"…. You want drugs…this is the only way to get drugs in any senible time frame. For an academic to develop a drug from scratch it takes many years…trust me I know. We have one and it is about 10 years on and it is still not yet in human phase I. To get the investment is where you spend half your energy. (Even with Pharma geting budgets are an isssue too but they have mchinery to do this in a timely fashion)) and academics do not have the skill-set or knowledge to do this alone.So if drugs were made as consequence of promise 2010 it could be 2015 and your human trails would not have started. Phase I 1 year, phase 2 may be 3 yeaars, phase 3, 7 years, regulatory review 1-2 years. We have been through this many times on the blog…. search on "Drug-the Game". To speed this process you have to get the mechanism of drug development changed."What is a time frame for accessible"….only a fool would give specific dates because no one knows but to answer your question it depends on which ones workIf it were Gilenya then the trial in PPMS is fully recruited and is due to finish at the end of september 2014 according to Clinical Trials.gov then you need the regulatory approval.Restoring lost function….the Edinburgh/Cambridge group have undertaken trials with stem cells already.If it was not for Promise MS you would not have the "SMART-trials" which has already been about 5 years in the planning. The "International collaborative" may not be where it is there are many positives that has come from this initative
You can't rush the scientific process! Science takes time. In addition, you can't put MSers at risk with unproven treatments. So no guestimating on the time. The BigPharma funded trials will report soonest – 2015 for fingolimod.
Prof GI find this sad. Firstly,that for those with progressive MS, and those with RRMS, the earliest any treatment will be available to provide neuro-protection is 2015. And this depends on successful trials and approvals (licensing and funding). Researchers and patients have a totally different view on timescale. I'd happily take an epilepsy drug if it offered so hope e.g. Phenytoin. Wait, wait, wait…. I don't want to get worse, but no one cares. Glad to hear that I won't be put at risk,
If BG-12 is neuroprotective as Biogen would have us believe it could be 2013.
Perhaps we should have a poll – has Promise 2010 made any difference to your disease? Do you expect the work flowing from Promise 2010 to have any impact on your disease within the next 5 years?MS for us is a disease of the hear and now – time isn't on our side. The urgency doesn't seem to flow through to the research world. I'm going to make the most of my life with MS and MS research can do what it wants (a bit like MS).
If you are on one of the trials then it may well do.Urgency does not flow through to research world. We are not time travellers I am afraid. but …..then what are you going to do! It seems that you need to get behind something like the the BPA and get change in the development and regulatory pathways. It needs international Political Involvement.
Be aware urgency and gung ho…often leads to failure and may even kill the technology leading to the benefite we want to deliver.
Prof G,Your slides list 3o or so other researchers who I'm guessing were also funded by Promise 2010. Have they delivered in accordance with what they were funded to do?Is there any way that bringing findings from bench to bedside can be speeded up?
BPA
Sorry for kicking you while you're down, but as someone said above PPMS is the poor relation and could be argued as the 'Elephant in the room'. Untill we see you understand PPMS and (take progressive MS seriously) (Prof G's words) I feel you are decades away. Sorry to be so realistic.Regards as always.
I'm not down…actually I am quite happy and the moment. I am hearing some good science.I agree we need to understand progressive MS both PPMS and SPMS. Decades away…you said it not me but…we have given time lines for any drug development and the development processes.Having listened to some talks this morning I think you MSers need to understand what the current reality of stem cells therapy is.The vast majority is in my opinion hype. Can they offer benefit..sure they can but in many cases the cells cannot get in the brain so they are not going to be turing into new myelinating cells or nerves, which MSers think is happening. I believe we will be managing expectation again, again as we will never deliver enough, fast enough.
Forgive me for saying this, but the questions and comments are childish All want a cure NOW because none of us has time. But this blog has helped me to understand why things take time. At least Team G is trying to speed up the process, with the LP idea, repurposing old drugs, BPA, etcAn old boss of mine once told us what to say to clients who set impossible deadlines and asked us to increase the team size for their projects:'Tell them 9 women can't make a baby in one month'
'Childish' isn't the vibe I was getting from the above comments, perhaps 'Frustration' is a little nearer ?Deadlines I'm afraid make the world go around and if one continually fails to meet theirs, you find a diminishing client base. The real world, where supply and demand are king.
Well said Andy. The notion that an individual should be talked down to for demanding clear answers is symptomatic of how the modern age is right now.One can understand that the time taken from inception to eventual completion of an MS drug is lengthy, however, the treatments being compiled to inhibit progression have been around for decades. They have cleared mandatory licensing hurdles and require a manageable process of re-appropriation. This is not rocket science and I think it's shameful that the work done in PROMISE 2010 is only now leading to human MS trials. Upon completion, progressive MSers will wait even longer for NICE to sanction their use on the NHS. We're talking years here.My thoughts regarding drugs in MS are pretty clear. I'm even reluctant to endorse drugs being hatched to treat progressive MS. I do think that we ought to wait until remyelination strategies become a reality, but if we're to believe Gavin Giovannoni's science diatribe, the existing compounds he's trialling in progressive MS will automatically encourage the bodies existing stem cells to come back to life and start remyelinating surviving nerves in the CNS. It's a beautiful concept, but Giovannoni doesn't exactly have a brilliant track record on delivering on his beliefs. His most recent change of opinion regarding DMTs ability to curtail progression is emblematic of that. Once again, I actually wish Giovannoni luck in his endeavours because if he is right then it'll be the biggest sea change in multiple sclerosis treatment and understanding ever witnessed. The world will never be the same again and every MSers quality of life will be changed for the better, forever.But let's be realistic. Giovannoni has difficult odds and his MouseDoc sidekick's disastrous doings on the CUPID trials is also indicative of bad omens at play. Even MouseDoc: Part II doesn't have a cracking success rate when we consider he was severely active in the CUPID shenanigans.Anyhow, back to my day job for now (I'm writing an essay on pornography's economic predicaments in the 21st century). Don't let the bullsh*t get you down 'fellas. I'm offering constructive criticism. If you lads succeed then I'll be the first to apologise for being a nasty and obnoxious prick.
"His most recent change of opinion regarding DMTs ability to curtail progression is emblematic of that."That was for the original DMT's such as beta interferon, he certainly does not believe that the new generation of effective DMTs will not affect the rate of progression and nor do I.Honestly, reading some of these comments I wonder why I bother keeping going with our research. It's miserable enough not knowing if you're going to have a job next year as it is. If everyone packed it in there wouldn't be any progress at all so think on!
Sorry to hear that MouseDoc2 – but it's even worse not knowing if you're going to have a job next year and to have MS on top of that as it happens to be in my case! I just hope that brighter days will come!
Andy, my 'childish' comment was directed more at the others than at you. I understand and share the frustration, but frustration is no excuse. Temper tantrums and other childish behaviour go hand-in-hand with frustration.
Cheer up MD2, it could be worse as Anon 1:22 says.I have a view on why Prof G so publicly dissed old school dmts and has lauded the new generation in quite the manner he did, but that might be too cynical. 'The King is dead, long live the King'Regards as always
I didn't think it was Anon 2:14, merely pointing out I think you were wide of the mark. No Childish temper tantrums here, just a heavy dose of realism. I totally agree, if anyone is looking for the fairy tell ending where the Prince carries off his bride to a life of happy ever after is probably on the wrong blog page. Keep up the work fellas, and don't take the criticism personally, after all you're not rounding up sheep.
In my view the old DMTs were at best of limited usefulness but they were the only things available at the time. This situation has now changed.It gets a bit wearing coming on here day after day and being slagged off left right and centre. It doesn't encourage you to come into work weekend after weekend (which I have done for more years than I care to remember) to try and find something that will make a difference to progression. I'll keep doing what I do and frankly I don't give a stuff if some don't think it's good enough. Whatever we do it never will be good enough for some and I guess that's just the way it is.
Dr DreMaybe you can be a sugar daddy with your millions from (c)rapping.but without resource we can't do much. As we know money does not grow on trees maybe in your world this is not a barrier, but it is in the real world.Give me two-five million for a trial and another two for the regulatory filing and perhaps I could start a study that will make a change. I will ask and you will pay-up rather than haing to beg over 5 years or more. Maybe time to put up if you want action or shut up.Look at the CUPID data in Prof G talk you have the slides. I know you do not get sound but again I think you are wrong and shooting from the hip (is that the Hop) I do not think it did nothing and I really resent the accusations that I or MD2 had anything to do with the failure (or success) of CUPID. We were not consulted at any part of the process, so get your facts right! You suggest it is wrong to be talked down too but you are doing just that! This effects me more that you know, if that trials fail…all our hard and others work identifying and validating the science and the target for someone else, who has not made the science, to turn it into rubble. No-one will be interested in cannabinoids for this indication no more oppertunities to develop this, no more oppertunities for us to get grants, no more oppertunities to develop the science, no interest from companies to develop alterative drugs, 12 years of our lives pissed away. Whats more MSers less likely to get access to a set of drugs that should do something positive.We hear about the RXR remyelination potential for studies by Franklin and ffrench constant, which you seem to like. However this is published and now any clinician with the ear of pharma, there are plenty of professional trialists out there, who have a drug can do this. This is without the need to have Franklin/ffrench constant anywhere near guiding the trial. It gets messed up because of trial design..where is your remyelinating therapy now…it in the bin..is that frustrating for you?.Buttons have been pressed.It is not just you who are affected by the clinical failures!However soap boxes cost nothing…progress does..
In defense of Prof Z who did the CUPID trial, this is where the CAMS trial led his ideas and as to trial design we are learning from the failures. He got off his bum and tried something so this needs to be applauded. In 2003 it was CAMS which failed in 2012 there was MUSEC that now worked. Is there going to be a CUPID 2 once we work out how to do the trials? This is out of our hands it was never in them. Furthermore we need to see what is presented from the CUPID trial before we start saying too much.
Alright MouseDoc, don’t have a cow, man. Sorry I spoke.I’m not trying to undermine ya’ll, just trying to point out basic observations. I can’t give you the kind of money you need, at least not in the sums you’re requesting. You may say that I ought to “shut up” then, but I have every right to state my opinion, do I not? I’m neither abusive nor threatening, though I do have habit of being provocative, I suppose.I have hit a raw nerve. Look, I’m just trying to get by just like you. I realise the current climate has made your professional security more volatile and the threat of redundancy is vexing all of you. That sucks. Dudes that have studied and accomplished as much as you guys should have job security, but we live in a world where the idiots that brought about a near cataclysmic economic maelstrom are the ones to be rewarded while highly educated peeps like yourselves are threatened with P45s. It’s not fair, I know.I do like Franklin and his achievements. You insinuate that his work is on the cusp of being made a pig’s ear out of because it’s now in the public domain and ready to be messed up by greedy pharmaceutical sociopaths, but I say let’s not wish it failure. Don’t be so jaded, man. Let’s hope that Franklin is the dude to finally put some cheddar in all our sandwiches, including yours MouseDoc.Let’s be friends MouseDoc. Let our better angels cut through all the nonsense and let’s get this party started. Start pushing the awesome compounds you keep bigging up and let’s get some myelin back on to these poor MSers nerve fibres. Stay loyal, stay focussed. Peace out.
"You insinuate that his work is on the cusp of being made a pig’s ear out of because it’s now in the public domain and ready to be messed up by greedy pharmaceutical sociopaths"I have no idea where Prof F is or an other person in their translational hope it was hypothetical on my part, but Prof F is a Vet and not a Neuro. It does not have to be pharmaceutical sociopath, well-intentioned meuros can mess it up also. If someone gets funding to do the study there is nothing Prof F can do about it and probably will not be aware of it until it has all been planned.Until the trial design is right we destine things to the bin. I need to write a review on this.
I wish those MSers who are feeling frustrated and are taking it out on Prof G,MD&MD2 would stop visiting the blog. Why don't you go on the MS Soc. website or get in touch with your MPs about the lack of progress with progressive MS, and the problems with the licensing authorities (and see how far that gets you). They are the ones with the money and the power to do something. I don't know how many times Prof G and the others have explained the length of time it takes drugs to get to market, and I am grateful that they take the time out of their day to explain the science and to interact with MSers and their concerns. They probably get frustrated by the lack of money and the beaurocracy that inhibits their progress in all areas of MS research.As for Dre, I wonder if he even reads the blog. The old DMTs are fairly useless re progression and disability.The new DMT's may halt/slow down progression and disability, but its too soon to say. Look at the research results, they do substantially reduce relapses which will probably halt/slow down progression, but too soon to say.You need 3 things in this order 1. stop inflammation 2. neuroprotection 2. repair. Doing 3 without 1 or 2 would not work.I remember years ago when the MS Soc used to do a question and answer session every few months with an expert on MS. Dr Franklin said then that the way forward was to pharmacologically induce the brain to produce more neural stem cells rather than try and transplant them.
Good post and thanks for the positive comments. I'm cheering up!Have a good weekend all.
Ok, now, after the ranting (again) what are the goals for 2013 Team G? Which important results are expected to appear or which novel drugs should be ready by next year (omitting the regulatory process just from a researcher's point of view)? Personally I set my hopes in Dr. Chataway (no illusional hopes just logical ones) because stopping/slowing progression is a more tangible goal than neuro repair. We all need to calm & carry on!!!
When we have time to reflect and consider things over the Christmas break we will prepare a few posts to address this.