Tuesday, 17 September 2013

The good news we have all been waiting for: the eagle has landed!

The eagle has landed: European Commission Approves Alemtuzumab. #MSBlog #MSResearch

"My sincere congratulations to Dr Alsadair Coles and Prof. Alastair Compston for their patience and perseverance and to all the MSers who volunteered for the studies to get this drug to market. Also to Genzyme for taking the risk given Alemtuzumab's profile and the investigators for committing and believing in the drug."

"Let's hope Genzyme and NICE come to a quick agreement on the cost-effectiveness debate so that we can start offering this drug to MSers with active MS. Please note that Alemtuzumab is indicated for the treatment of adult MSers with RRMS with active disease defined by clinical or imaging features. The big word in the previous sentence is OR; this means that regulators have finally accepted sub-clinical MRI activity as disease activity. Let's hope NICE agrees. If NICE don't are you up for an MSer-led street protest? If you are I am prepared to front it."




Press release: CAMBRIDGE, Mass., Sep 17, 2013 (BUSINESS WIRE) -- Approvals Set the Stage for Launches Throughout EU and Strongly Position Genzyme as a Committed Partner to the MS Community

Genzyme, a Sanofi company announced today that the European Commission has granted marketing authorization for Lemtrada(TM). This follows the August 30th approval of Aubagio(R). The company intends to begin launching both products in the EU soon.

"The approvals of Lemtrada and Aubagio in the European Union represent an important milestone for Genzyme and demonstrate our focus on scientific innovation and commitment to multiple sclerosis patients," said Genzyme CEO and President, David Meeker, M.D. "This is particularly exciting as the EU approval is the first for Lemtrada globally. We look forward to making these unique therapies available to MS patients very soon."

Lemtrada is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features. Lemtrada 12 mg has a novel dosing and administration schedule of two annual treatment courses. The first treatment course of Lemtrada is administered via intravenous infusion on five consecutive days, and the second course is administered on three consecutive days, 12 months later.

The Lemtrada clinical development program included two pivotal randomized Phase III studies comparing treatment with Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif(R)) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II), as well as an ongoing extension study. In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.

The most common side effects of Lemtrada are infusion associated reactions, infections (upper respiratory tract and urinary tract), lymphopenia and leukopenia. Serious autoimmune conditions can occur in patients receiving Lemtrada. A comprehensive risk management program will support early detection and management of these autoimmune events.

Aubagio 14 mg is a once-daily, oral therapy indicated for treatment of adult patients with RRMS. The EU approval was based on data from the Phase III TEMSO (TEriflunomide Multiple Sclerosis Oral) and TOWER (Teriflunomide Oral in people With relapsing remitting multiplE scleRosis) trials. The EU approval of Aubagio includes new active substance designation.

"Multiple sclerosis necessitates a highly individualized treatment approach, and the increasing diversity of options is good news," said Hans-Peter Hartung M.D., Ph.D., Professor and Chairman of the Department of Neurology at Heinrich-Heine-University in Duesseldorf, Germany. "The Lemtrada clinical trial data support its potential to meaningfully address disability in active RRMS patients, while Aubagio's efficacy, safety and convenient dosing may provide an important alternative to injectable therapies. The approvals of Lemtrada and Aubagio represent a significant step forward in the way we think about treating this disease."

For full press release see following Genzyme press release:


CoI: multiple

45 comments:

  1. There is nothing momentous about this news. The drug is a dangerous substance. It is overpriced and will hopefully languish for years in NICE's approval pile.

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    1. Killjoy; alemtuzumab may offer a cure, why would you deny someone the choice?

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    2. How is alemtuzumab a cure? Who will it cure? How will it cure them? Is there a guarantee such an expensive drug will cure the sufferer? Will the pharmaceutical company reimburse the tax-payer if the drug fails to work?

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    3. I can't answer this question, but the experiment is running. We will know the answer in about 10 years time with the current cohort of alemtuzumab-treated MSers from the trials. If a large proportion of them stay free of disease activity we can call it a cure and if the comeback with secondary progressive MS we have gotten the autoimmune hypothesis wrong.

      The question is if you had MS would you be willing to wait 10 years for an answer when the window of opportunity for responding to alemtuzumab may be very narrow?

      http://multiple-sclerosis-research.blogspot.co.uk/2013/02/neda-defining-cure.html

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    4. ^^Reminds me of the guy who would follow the Roman general during a triumph procession saying, ""Respice post te! Hominem te esse memento! " It's just meant to keep the heroes humble. Personally, I am happy for you all and can't wait for it to get approved here in the U.S.

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    5. http://kindofafireguy.wordpress.com/2012/03/13/memento_mori/

      “Respice post te! Hominem te esse memento! Memento mori!”

      “Look behind you! Remember that you are but a man! Remember that you shall die!”

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    6. Re: "The drug is a dangerous substance."

      Incorrect it would not have gotten a EU license if it was dangerous.

      "It is overpriced and will hopefully languish for years in NICE's approval pile."

      I am not aware that a price has been announced. If you have this information I am sure a lot of readers including myself would be interested to hear.

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    7. "If a large proportion of them stay free of disease activity we can call it a cure and if the comeback with secondary progressive MS we have gotten the autoimmune hypothesis wrong."

      If the autoimmune hypothesis is correct, does that conflict with the thinking behind the Charcot project at all?

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    8. The major adverse effects associated with alemtuzumab (the active ingredient contained in Campath) have included infusion-related reactions, hematologic toxicity, and infections.

      Alemtuzumab has been associated with infusion-related events including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, rash, syncope, pulmonary infiltrates, ARDS, respiratory arrest, cardiac arrhythmias, myocardial infarction, and cardiac arrest. Some cases of cardiac adverse events have resulted in death.

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    9. These reactions are seen in cancer patients who receive about 10x the dose. In MS were a much smaller dose is used the infusion reactions are milder and largely suppressed by pre-treatment with steroids. The best of my knowledge there have been no deaths due to infusion reactions or allergic reaction in the MS population.

      You need to remember that alemtuzumab is often used as part of the conditioning protocol for bone marrow transplantation.

      If you want to reboot your immune system there is not easy or completely safe way of doing it.

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    10. This is great news for patient that Alemtuzumab has been approved for those who will benefit. However, please spare a thought for those who this treatment is not suitable. Whilst you say that 1 in 7, 1st and 2 degree relatives will get MS, surely we don't want them to get it at all. 1 in 3 of us will get cancer and I would hate to see patients sue heir doctors, NHS and drug companies because they have had a treatment that directly alters their immune system. I hope Alemtuzumab works, but I hope patients receiving it have eyes wide open.

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  2. With Alemtuzumab who needs steroid treatment?

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    1. When you are given your infusions of alemtuzumab you are pretreated with intravenous steroids to reduce the infusion reactions. Unfortunately, not everyone is rendered relapse free; the annualized relapse rates are reduced to about 0.1; i.e. 1 relapse every 10 years.

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  3. Well, that's fantastic news. Fervently hope NICE play ball and it's available to as many MSers that can benefit asap. I too am willing to take to the streets if NICE don't play ball.
    I hope the pricing is sensible and not profit-gouging.

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  4. Prof G, how is this momentous news? Why should we MSers that are beyond this medicine's window of effectiveness actually campaign to get it onto NHS approval books I have followed this blog for almost half a decade and this news is all we have got in "good" news. This is terrible.

    I will not waste my time campaigning. It won't benefit me. I can't care less if alemtuzumab gets British approval. It's a total waste of time.

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    1. My thoughts entirely. To deny someone the possibility of a treatment just because it won't benefit you is the last word in mean-spiritedness.

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    2. We live in a society where one has to look out for themselves. I will not campaign for a drug that will not benefit the majority of current sufferers. It is not worth my time. Give me something that helps all MSers then you have deal, but no way am I going to fight for future MSers. Their battle belongs to them, mine to me.

      You are on your own on this one, Prof G. Alemtuzumab can't help me so therefore it can sit on the shelf for all I care. The MS game has lost much favour with most of us. It has been a great big disappointment.

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    3. You're all heart. Your altruism is an inspiration to all.

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    4. They are just bitter MD2. It's something I encounter often on other blogs as well - it's quite understandable though. As with other things in life it is the same with health - people are just envious and bitter if opportunity escapes them. Sometimes when I read about CIS people I also get wistful but not that bitter hopefully. It's human but not nice. Alem is great news, though. Hope in a FEW years time progressive MSers will get there Eureka moment.

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    5. In a way, selfish comments like this person's help the rest of us. It reminds us of what we can become if we start to let ourselves think negatively. It is a fine reminder to try to not let this disease get to us mentally.

      More on the topic, this approval is wonderful news! Hopefully we get the same good news later this year here in the US. Thanks for all your hard work Team G!

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    6. Did you know that 1 in 7 people with MS have affected 1st or 2nd degree relatives? What about them? If we all had this attitude society would grind to a halt. Altruism, where has it gone? What is happening to the world?

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  5. Prof G, how many RRMS people that you've treated with alemtuzumab went on to develop SPMS?

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    1. Admittedly a few; all were treated late. However, the vast majority are doing very well, particularity those treated very early. Most have no evidence of disease activity (NEDA).

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    2. This statement speaks volumes. I am glad that you have admitted that alemtuzumab is not a panacea for MS the way readers of this blog think. The truth is that even without alemtuzumab the majority of MSers do well for a few decades that follow. Alemtuzumab seems like another overhyped product that many money-makers are pushing relentlessly. It is a dangerous medicine and has many major side-effects. You are wrong to paint it as harmless. It's very unprofessional of you to do that.

      NICE will drag its feet on this one. Your claims of 2013 being momentous are unfounded. This post should be retitled 'The Ego Has Landed' because the licensing of alemtuzumab has more to do with your personal aggrandising, Prof G. It has little to do with sufferers of MS.

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    3. May be it is time for the MSers who have been treated with alemtuzumab to respond?

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    4. There have been quite a few MSers who have been treated with Alemtuzumab that have posted here previously (with positive responses).

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    5. "This post should be retitled 'The Ego Has Landed' because the licensing of alemtuzumab has more to do with your personal aggrandising, Prof G. It has little to do with sufferers of MS."

      We should have an alternative comment section entitled Churls Corner which you will be free to contribute to. These negative comments emind me of the "What have the Romans ever done for us?" section of the Life of Brian.

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    6. Prof G can you quantify 'treated late'? Is this 1 year, 2 years, 5 years after diagnosis?

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    7. "Prof G can you quantify 'treated late'? Is this 1 year, 2 years, 5 years after diagnosis?"

      I'd be interested to know this too. Do you measure "too late" by time since diagnosis? Number of relapses? Imaging features? Accumulated dissability? Other?

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  6. Oh brilliant! I applied for the trial in 01. I still have relapses and I am keeping my fingers crossed that I can finally get to be treated with Lemtrada. Slight lump in throat now.

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  7. I would like to know what is the likelihood of getting cancer or some other serious infection after a year-long treatment with Alem. I have an aggressive RRMS and am thinking now a bit more seriously of choosing Alem over Gilenya.

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    1. You only have a short course of Alemtuzumab each year and you do not constantly take it. So whilst the influence of the drug is long lasting the drug does not hang about forever and so the remaining cells have the capacity to deal with infections, but there more people reporting infections than the interferons in some of the trials, but these on the whole not of major cause for concern and likewise there is a cancer risk which is of a similar magnitude to other highly effective DMT and remember that there is a cancer risk inherent in life.

      ProG may have a comparison of adverse events, or talk to you neuro.

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    2. How about reactivation of cytomegalovirus. CAMPATH studies indicate that up to 29% of patients experienced symptomatic reactivation of CMV.. That seems very concerning. Guess why one needs to take Antiviral treatment with Alemtuzumab. CMV is a causative agent in viral encephalitis

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    3. What do you mean anon 6:13- it's not standard protocol over here to give antivirals with alemtuzumab? IV steroids, paracetemol, anti emetics and anti histamine was about it, unless it's now changed. Also I've not heard of any cases of viral encephalitis post alemtuzumab for MS?

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    4. The CMV reactivation is an oncology problem. The dose of alemtuzumab in oncology is >1000mg over 12 weeks. In MS we use 12mg per day x 5 days in year 1 and 12mg per day x 3 days in year 2. The most you get in a year in 60mg compared to more than 1,000mg in leukaemia patients. Please don't get the cancer profile confused with the MS profile.

      http://www.campath.com/pdfs/Campath_Dosing_and_Administration_Guidelines.pdf

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    5. Lexie we give MSers treated with alemtuzumab 28 days of an antiviral whilst their counts are low to cover against herpes reactivation. We don't cover CMV reactivation.

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  8. I am waiting to go on Lemtrada. BRING IT ON! Like every MS drug there are side effects and everyone has to make their own informed decision. My neuro is encouraging me to go for it and I trust her, she is well informed and doesn't sugar coat, doesn't make false promises either.

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  9. This is excellent news that another option will soon exist for us to atleast choose from. I'm very happy for my fellow msers in the UK to have this option soon, and look forward to when the FDA accepts its use for treatment of MS so we in the US have the same option. If any place might need campaigning to make it affordable it may be here!... but one step at a time! One question I did have Prof G. I haven't seen it posted or discussed too much, but is it true there may be some damage done to male reproductive tissue with Alem?

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    1. I learn stuff new all the time......CD52 on sperm

      I'll leave ProfG to comment as he no doubt is more aware of the literature on the pros and con of Alemtuzumab

      Mice homozygous for CD52 are viable with no gross abnormalities and no defects in sperm development or function.

      Yamaguchi R, Yamagata K, Hasuwa H, Inano E, Ikawa M, Okabe M.
      Cd52, known as a major maturation-associated sperm membrane antigen secreted from the epididymis, is not required for fertilization in the mouse.Genes Cells. 2008; 13:851-61. doi: 10.1111/j.1365-2443.2008.01210.x.

      CD52 is a glycosylphosphatidylinositol (GPI)-anchored antigen expressed on lymphocytes and in epididymal epithelial cells. CD52 is also known as "maturation-associated sperm antigen" but its function is unknown. We therefore generated Cd52 disrupted mice. The resulting Cd52 null mice were healthy, even though Cd52 is expressed on cells of the immune system. We then examined a possible role for CD52 in reproduction. Sperm from Cd52-deficient males were investigated and the viability, motility, morphology, and incidence of spontaneous acrosome reactions were found to be all similar to values for wild-type sperm. In in vitro fertilization system, the sperm showed normal fertilizing ability. As CD52 was found to be transferred onto sperm only after they had migrated into the vas deferens, we examined the behavior of sperm from Cd52-deficient mice in vivo. The mice mated naturally and we observed that a normal number of sperm passed through the uterotubal junction, known to the crucial hurdle for various gene knockouts resulting in infertile sperm. As a consequence, there was no difference in the litter size from the wild-type and Cd52-null males. Our results therefore indicate CD52 is not required for fertilization in the mouse either in vivo or in vitro.

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    2. Re: male reproduction

      It is true that there is CD52 in the testes, but this not affect male sexual function. There have been several births post alemtuzumab when the recipient has been the male. There will be study on sperm function post-alemtuzumab presented at ECTRIMS in Copenhagen. I will report on this in more detail after ECTRIMS.

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    3. Before my son had alemtuzumab I was concerned about its effect on sperm and even went so far as to look into the cost of sperm banking. However, I emailed Alisdair Coles about this and he said he didn't think it was necessary to sperm bank.

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  10. Exciting a therapy that targets CD52 on B-cells and T-cells. Finally all the work by researchers is bearing fruit. Hopefully anti-CD20, rituximab or its counter part ocrelizumab will follow. Hopefully, "One small step for man one giant step for MSers". Let's keep the pressure on to push forward.

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  11. I would have Lemtrada like a shot if offered it. Life is full of risks, just like all aggressive medications.

    I applied to go on the Campath trial (Care MS2, I think it was called?), but it never happened.

    I was fit and healthy back then, but the aggressiveness of my illness has left me borderline SPMS. I fear this is one boat I may have missed.

    *pulls sad face*

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    1. Sorry to hear that Dan. Maybe not everything is lost yet!

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  12. – In recently published clinical trials, single-agent Campath® (alemtuzumab) was associated with an incidence of symptomatic CMV reactivation that ranged from 4% to 29%. CMV is cytomegalovirus and is common in the general community. Is this not concerning???

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