Friday, 25 January 2013

UCLP Bosses speak out against the actions of Genzyme

Thompson AJ, Giovannoni G. Removal of access to alemtuzumab for patients with aggressive multiple sclerosis. BMJ. 2013 Jan 18;346:f275. doi: 10.1136/bmj.f275.

Team G speak out. 


Although some treatments are now available for multiple sclerosis, better treatments are needed for people with aggressive disease. The need to find agents that can prevent or slow disease progression is particularly challenging and requires a concerted global effort that combines academic and pharmaceutical expertise. Although such partnerships are rare, the story of alemtuzumab has shown, inspirationally, that academic and pharmaceutical prowess can be combined to deliver an agent with real promise. Alemtuzumab, which has been used successfully off label to treat active relapsing-remitting multiple sclerosis, is a humanised monoclonal antibody that targets the CD52 antigen on leucocytes. Not surprisingly, there was therefore an outcry when Genzyme, now a Sanofi company, surrendered the licence for all currently licensed preparations of alemtuzumab, with effect from 8 August 2012, meaning that it will no longer be available as a licensed product in the United Kingdom once existing supplies run out.


This withdrawal was not related to product safety, efficacy, or supply, but was part of Genzyme’s plans for bringing alemtuzumab forward as a treatment for multiple sclerosis. It was done in agreement with the Medicines and Healthcare Products Regulatory Agency (MHRA). When stocks run out, alemtuzumab will still be available through a named patient access programme for its cancer and transplant indications. But what does this mean for people with multiple sclerosis in the UK?

It means that off-label use of alemtuzumab in patients with multiple sclerosis has come to an abrupt end. Patients and clinicians will have to wait for the new formulation (Lemtrada) to be licensed by the European Medicines Agency and be approved by the National Institute for Health and Clinical Excellence before it can be accessed on the NHS. (Years away)

The removal of access to off-label use of alemtuzumab is a complex matter. It will not surprise anyone if the new formulation of alemtuzumab that is specifically for multiple sclerosis (Lemtrada) costs more than the old formulation (Mabcampath) when launched. A cynical perspective is that the old formulation was withdrawn simply to allow the manufacturer to increase the price of the new formulation. Of course the argument is that Genzyme needs to recoup the costs of running the multiple sclerosis clinical development programme for Lemtrada and make money for its shareholders. If we want the drug industry to repurpose existing drugs for new indications it needs an incentive to do so. However, until we know what Lemtrada will actually cost any further debate on this matter is moot. (Bet you it will cost alot if word on the street is correct)

Mabcampath is not entirely safe. Serious, albeit treatable, adverse events have occurred in people with multiple sclerosis who have received alemtuzumab.These have included several life threatening autoantibody mediated autoimmune diseases, the most serious of which are immune mediated thrombocytopenia and Goodpasture’s syndrome. If licensed for the treatment of multiple sclerosis, alemtuzumab will almost certainly have an intensive and rigorous post-marketing surveillance programme. Patients treated with alemtuzumab for multiple sclerosis will probably need monthly blood and urine tests performed for at least five years after treatment to monitor for these complications. It would be difficult for Genzyme to implement this programme if an unlicensed formulation of alemtuzumab (Mabcampath) was simultaneously being used.

What about the ethical problem of patients who have already been treated with alemtuzumab who will no longer have access to it? This is important because alemtuzumab is an induction therapy—it is given as a course of five daily infusions at the beginning of year one and three daily infusions at the beginning of year two.(Ironically, patients with multiple sclerosis will be offered a third, or subsequent, course of the drug only if their disease is active—if they have a relapse or have evidence of disease activity on magnetic resonance imaging, which is counter intuitive.) Genzyme and the relevant healthcare providers must come to an interim solution that allows patients with multiple sclerosis who have had a course of alemtuzumab infusions but need additional courses to receive the drug on a named patient basis before it is brought to market for the new indication. The onus will then be on the treating clinicians to make sure that patients are monitored appropriately for any delayed complications of alemtuzumab treatment.

The withdrawal of alemtuzumab has generated a backlash from the multiple sclerosis community. However, we would encourage a broader debate on the questions that this and other related cases raise about the role of the drug industry in drug development—particularly in the repurposing of existing drugs—including relations with academia and the industry’s role in the wider economy. On a positive note, the alemtuzumab multiple sclerosis development programme is an excellent example of how academia and the drug industry can work together to find new treatments, with benefits on both sides. What started as an academic initiative in the early 1990s was successfully transferred to industry and has resulted in a promising treatment for people with multiple sclerosis. Perhaps future models might be based on partnership throughout the entire drug delivery pipeline.


I think this is a sorry state of affairs, but companies want to make money that is clear......however it is right for BigAl and ProfG to raise questions. Will Teva make a citizens petition to the FDA against it or maybe Novartis and Biogen will make a case as it will compete with their product?

This is why we need the BPA (see above), that can even move into the Big Pharma space. 

Maybe the As from Cambridge are a bit embarrassed about this whole process of profiterring, because if seems that at least one of the As is keeping an unusually low profile, with regard publishing the effects of alemtuzumab or is that Lemtrada-which is less alemtuzumab at ten times the price?

Also they are lucky it is a biological because had it been a chemical, the patent life would be gone by now and the me-toos would be on the table?

CoI: Written by Team G

45 comments:

  1. Yes, I heard that Dr Coles is on sabbatical for a year, probably to avoid being part of the Lemtrada it machine...maybe he is making a moral stand

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  2. This post almost reads like a debate between 2 people who are alternately speaking for/against Genzyme

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  3. Copyimg a biological is well within the capabilities of companies in India and probably other places too. Once the product is licences and succeful they will come into the market

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  4. If there is a patent is still active then there should be protection worldwide and countries should not flaut this principle, but would it be identical because if it isn't then it is different and hen trials may be important.

    Have we got copies of tysabri?

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    1. Tysabri is still in patent (i think). Alemtuaumab is out of patent.

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    2. I think the team said that monoclonal antibodies can't be reproduced for the market without further clinical trials of the 'me too' drug as they are biological. I presume it's all the drugs that end in 'umab' ie alemtuzumab, natalizumab etc. Too costly for the drug companies, therefore, not going to happen so the pharmas that own these drugs in or out of patent have a monopoly. Too bad IV cladribine is out of patent- it's chemical and so could be reproduced, but no pharma's interested

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    3. Keep watching this space regarding Cladribine!

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  5. Pray, do tell Prof Giovannoni, how was the Christmas hamper sent by Biogen-Idec last month? Nay, at least tell us Novartis remembered to keep you on their Christmas card list?

    You have defended and collaborated with greedy pharmaceutical corporations your entire career, informing sufferers of MS that such industries have the patient at heart and consist of good people wanting to rid the world of terrible disease and suffering. It's all hogwash and the only real intent is to generate mass profit at the expense of vulnerable people. These pharmaceuticals want money. They want the illness to continue, only to be perhaps held at bay with the constant aid of the drugs they are peddling out. Drugs that don't even clinically remedy the disease in question.

    I say this is a brilliant example of why all MSers need to boycott expensive drugs. These drugs are not fixing your MS and they never will. They are just putting you in a false sense of security, whereby, because you're told the drugs are efficacious, you therefore believe that to be true. It keeps neurologists in work and maximises huge money for executives.

    To hell with Genzyme. To hell with every pharmaceutical tyrant feeding poison to MSers not in a position to know any better. There is no cure for your disease. Don't let them fool you into thinking there is one.

    I hope that NICE doesn't greenlight Alemtuzumab. I hope the Sanofi mafia gives up on Britain and focuses its trickery deeds elsewhere, perhaps in America where their greed will be most welcome. To be honest, Alemtuzumab won't get a UK licence in this life. These are the times of austerity and the government will rightfully withhold access to a poisoness concoction like Alemtuzumab, and so they should.

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    1. Dr Dre you should keep quite and only comment on issues you have experience with. I have been treated with Alemtuzumab. My only regret is didn't get treated 3 years earlier when I had my first attack. I am now relapse free and have made a reasonable recovery from my major attack. I sincerely hope others like me get the option of being treated with the drug.

      Prof. G I would ignore Dr Dre; keep-up the good work.

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    2. I agree. I too have been treated with alemtuzumab. I wish it was an available induction therapy as I wouldn't have the neurological problems- albeit minor- I have now. Dr Dre- is MS not your disease too? What alternatives are you suggesting to pharmaceutical ones? Diet and CCSVI?

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    3. perhaps dr dre wants us to bycott the drugs because he has shares in wheelchair, walking stick, eye patch etc companies :-)

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    4. Dr Dre is not suggesting any alternatives. He says MSers should resign themselves to their fate

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    5. Can I suggest that in future we ignore Dr Dre? We are giving him/her too much airtime. Cam I suggest that VV & Dr Dre meet? A match made in heaven?

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    6. Can I suggest you please list all the available treatments available to someone with progressive MS.
      I'm here all week so you've got plenty of time to do your research.
      Look forward to it,
      Regards as always.

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    7. Another Alemtuzumab patient - relapse free for 5 years. As above, wish I'd had it earlier. Won't have a word said against Dr Coles. See him every year and think the world of him.

      Compton/Coles are my heroes - prof g and prof mouse have yet to get any treatment to patients - hoping Charcot project or neuro-protection trials come good. Until then, you are in the shadow of the two great men in Cambridge.

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    8. Dr. Dre is stressing a clear, yet unpleasant fact: There is no effective treatment for MS, despite the plethora of expensive substances used. The rest is suffering.

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    9. If the truth be told Compston and Coles didn't get the treatment to patients; Genzyme did! That is the reality of drug development; without Pharma it does not happen. I think this blog has being trying to tell us this for some time now. So when Genzyme set the price of Alemtuzumab I would be very surprised if any academic has any input at all.

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    10. If it was not for Prof. Compston taking the brave step of trying Campath-1h in MS we would not be having this discussion. If it was not for Dr Coles' dedication and focus we would not be having this discussion. I agree they deserve all of academic credit of getting alemtuzumab this far. Genzyme, however, deserve credit as well. They have taken a massive financial risk; I am told that their investment to this programme is already well over $500,000,000. With alemtuzumab's side effect profile this was a brave decision. In short they should be thanked. Numerous other pharma companies held the alemtuzumab ball and dropped it.

      What about all the investigators and staff who worked on the alemtuzumab trials? This includes myself and the team at Barts and The London.

      Finally, the most important people that need to be remembered and thanked are the MSers who were brave enough to be treated with Alemtuzumab. Without MSers volunteering for the trials we would not be here today. Volunteering to participate in clinical trials is very altruistic; there is no guarantee that you will derive any benefit but you do it for the good of the field. Thank you. You, the MSers, are the real heroes of this story.

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    11. Prof g has yet to get anytreatment to ms. I suggest read the literature he wasinvolved with the devlopment of both tysabri and oral cladribine. Both we approved for ms but cladribine was withdrawn by the makers
      .
      His mentor said you get into bed with all of them or non of them.....so you have prof g the pharma ho:-)
      ps they cannot. Give christmas hampers

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  6. I get the profit motive but these are people's lives. At the least it needs to be available to people who have had the first course.

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  7. Who is Dr. Dre?. To be honest he has said what I thought, but I have been relapse free since I started on Tysabri so I am thankful for the pharma option. Does anyone know when Alemtuzumab will get a licence? Without that I guess the NICE debate is futile. Keep up the good work all. Peter

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  8. I was not dissing dr coles indeed a man with morals.
    Have i had ideas that have become drugs...yes
    can i give drugs to msers no.

    Andy enjoy the wait. I could list new ones for this year.

    dr dre it is like rap this comments all sounds the same:-)...just like his stuck record.

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    1. Please list them MD, then I can enlighten some Neurologists much in need.

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    2. You will need to get on the up and comming trialsypu can hear about them at the research day

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  9. ".....prof g and prof mouse have yet to get any treatment to patients"

    I would suggest that Prof mouse's seminal work on cannabis for spasticity greatly helped the approvals granted for Sativex around the world. That's just one example.

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  10. How charming! I return to this blog and convey a valid interpretation which results in a braying mob intent on personally attacking me.

    Not even Prof G will be foolish enough to state that every MSer treated with alemtuzumab has avoided developing progressive MS. I know for a fact that patients in his care that were administered alemtuzumab went on to become devastatingly disabled. Alemtuzumab is merely a gimmick. If the MSer stays in a stable condition then the ‘professionals’ say that the drug works, but if they become progressive then the very same neurologists then state that they were treated too late to reap the benefits of such drugs. This way they - the ‘professionals’ - can have their cake and eat it.

    Let’s be honest here. Even hundreds of years ago MS existed as a disease in which sufferers had bouts of disease activity that came and went. In that era ‘professionals’ declared the power of pray was a healer, whereas now they spin out some toxic medicine that performs a similar operation of smoke and mirrors. It’s all nonsense. Medicines for MS are about as useless as getting on one’s knees and praying to some non-existent God to cure you. Neither one works. It’s all in your heads, literally.

    The processes driving progression and relapses are different and misunderstood. Statistically, MSers treated with DMTs are still massively ill within a decade of diagnosis, enough to give up work and spend a lifetime on disability benefits. The biggest mistake visitors to this blog make is confusing relapses with progression. The two are independent of each other. That is why alemtuzumab treated MSers can often become progressive MSers.

    Prof G and his sidekicks hardly ever advocate living a healthy lifestyle and instead focus all their energies in detailing lethal concoctions they’re learning about that will most likely not take care of the fundamental causes of MS. They are being highly irresponsible, and some MSers using these toxic drugs are dying as a result. It’s no different from CCSVI peddlers that are doing the same thing. People’s lives are at stake.

    MS is incurable. That is the reality. You cannot cure a disease when you don’t even know why it’s happening. Alemtuzumab will not cure your MS. Many of you having taken alemtuzumab still have your residual MS symptoms regardless of relapse activity. Your MS is progressing in ways you cannot detect and no medication alleviates progression. That’s a fact.

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    1. "How charming! I return to this blog and convey a valid interpretation which results in a braying mob intent on personally attacking me."

      Given the highly opinionated nature of your posts with scant regard to much of the evidence, particularly with regard to the new generation of DMTs, what did you expect?
      You extrapolate data from the old DMTs and extrapolate to the new ones, which is hopelessly biased.
      As is clear it appears the majority here don't agree with you.
      It's far too early to judge whether alemtuzumab will really stop progression. It will take decades but judging from the comments here and the studies so far there is justifiable hope that this can make a real difference.
      You appear to have a severe case of Private Fraser syndrome ("We're all doomed, doomed I tell you").

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    2. I love it when posts end with "That's a fact". It rarely is ;-)

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    3. "...there is justifiable hope that this can make a real difference."

      There are Alem and Tysabri receivers who saw no benefit. Is this a fact, MD2? Can you explain why that happened to them? If not, you can't really be sure that those who benefited did good for the reasons you say they did, can you?

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    4. The effect of campath on progressive ms was reported years ago and because of this it was decided to go early after diagnosis and i have yet to here why this is nota good approach.

      The content of the blog is generated by publications and there is limited work published on neutriceuticals and life sytle and when it is the work is often poor quality that says nothing concrete. If you want to find out about life sytle etc there are plenty of sites on the web.

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    5. Dre is a bit of a controversial attention-seeker, but I do feel the whole 'let's wait decades and see if alemtuzumab does what it says on the tin,' to be really worrying.

      There are MSers who I read were treated with alemtuzumab and still became progressive, which means the drug is not a cure. Maybe it makes a difference to relapse rates (a very good thing, I say) but it's not solving the big problem.

      We need to stop the active progression or else it's all just manipulated statistics.

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    6. None of the drugs is a cure and maybe none of them stops progression.
      Doesn't matter - I'm happy to have anything that slows progression and postpones disability. That may just be good enough.
      After all, with or without MS, we will all age and get various disabilities.

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    7. Anonymous 5:56
      The thing is that Alemtuzumab seems to be very good at stopping relapses. The earlier you do this in theory the better the long-term influence on disease if you buy into the lesions are the sole cause of neuronal damage. For those patients who have been treated very early in their disease this may mean that any progression may have been stopped in its tracks BUT (and this is an important point) if neuronal death is occurring independent of lesions then this will grumble on and we need to do long-term follow ups to see if that is the case and where we will need to consider neuroprotective therapies as an add-on therpay to DMTs.
      The patients who did progress on alemtuzumab were treated later in their disease where the nerve death cascade may be too well established to prevent progression.
      Hopefully the data will show that if you treat early and aggressively there will be no progression and we can maybe start talking about cures.

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    8. MD2, there is nothing but pure speculation to support that any DMT will actually slow progression.

      If the CRABs havent been proven to slow progression (at all) why would an even more powerful DMT have the capability to do so?

      There is just no logic in this approach.

      If what you are doing is not working then stop doing it.

      If you are in this for the good of the patients its time to change direction. Its never too late.

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    9. "If the CRABs havent been proven to slow progression (at all) why would an even more powerful DMT have the capability to do so?"

      That's right Anon. New age DMTs are supposed to impact on relapse rate and lesion count as did old age DMTs, only a bit better. According to Dr Ebers, these metrics should not be used in drug trials since they have nothing to do with long term disability. Yet, pharma corps continue to use them because the can manipulate both the relapse rate and lesion count, thus creating a false image of efficacy.

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    10. "MD2, there is nothing but pure speculation to support that any DMT will actually slow progression."

      But how will you know if you don't try?

      VV the new DMTs are a lot better than the old DMTs at stopping new lesion formation. Again there needs to be long term follow up to see if there is an effect on slowing progression but this will obviously take time. In the meantime lets just give things a chance and we can decide which treatments are truly making a difference.

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    11. "But how will you know if you don't try?"

      The immune system as probable cause of MS is being studied since 1933. Haven't you tried enough? Do you have solid ground beneath your feet to continue trying?

      "VV the new DMTs are a lot better than the old DMTs at stopping new lesion formation."
      Prof Ebers says that this is of no importance. Is he out of his mind?

      "In the meantime " = 16 years from onset to progressive phase
      Now i can wait that time. Can everybody?

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  11. I agree, everything is about chemicals on this blog and too little focus on healthy living.
    How will healthy living, according to you Dr Dre, effect progression of MS?
    What exctatly does healthy living entail?

    We know you opinioin about pharmaceuticals by now but what can else can you chip in with?

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    1. I've always found regular breathing to be the secret of a long life.

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    2. Actually MD2 you're not so wrong - irony aside - regular breathing means relaxation which is good for soothing one's nerves! I wish I could relax more.

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    3. MD2, Its exactly this kind of ignorance and arrogance that troubles me. It may actually, I sincerly believe, come as a surprise to you that lifestyle effect risk and prognosis of most diseases.

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  12. Please MD2, there should be plenty for you to dig into yourself.
    However, as I know you guys like the lancet here is a couple for you

    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60766-7/abstract

    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60692-2/fulltext


    I'm sure you can find plenty yourself if you bothered.

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    1. Anonymous the 2 links you posted are related to type II diabetes not MS.
      If you find something similar that relates to MS I'll gladly have a look.

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