Saturday, 5 April 2014

How long does it take to repurpose a drug?

The alemtuzumab ultra-marathon is not over yet. What can we do to help American MSers? #MSBlog #MSResearch

"The history of alemtuzumab (formerly Campath-1H) is an interesting one and is an example of how long it can take to repurpose a drug. If you have the time I would recommend you watch this YouTube video or the article by ."




"You will have noticed that the first laboratory work that led to alemtuzumab's discovery started in 1979 with the first MSer being treated with it in 1991 in Cambridge. The culmination of this work is the NICE appraisal below stating that Alemtuzumab is a cost-effective treatment for adults with active relapsing remitting disease; 23 years to repurpose. The cost of the drug is £7045 per vial, this equates to £35,225 for the 5-day course in year 1 and £21,135 for the second and subsequent courses. About 65% of alemtuzumab-treated MSers will need just 2 courses over 5-years, 25% 3 courses, 10% 4 courses and very few 5 courses. In addition to the cost of the drug there are all the costs associated with infusions, treatment of infusion reactions, monthly blood monitoring, annual MRI scans and the treatment of the autoimmune complications. A rough calculation suggest to me that alemtuzumab is similar, or possibly cheaper, than natalizumab. Are we able to start prescribing it? No. NHS England has to adopt the NICE appraisal, this usually takes 3 months and there is a remote possibility given the costs of the drug in the first year that they may restrict access to prevent a run on the bank. NHS England works on an annual budget and it will hope that not too many MSers have been warehoused for alemtuzumab treatment."

"I would like to reiterate that the current hypothesis is that alemtuzumab is working via rebooting the immune system. When it reboots there is evidence that it changes the regulatory networks of cells; it is been hypothesised that these changes are responsible for its action. I am not sure that this is necessarily the case. One hypothesis I have proposed is that it may be working via B cells. Why? When you line up all the highly effective therapies in MS the only cell that is common to the action of all of them is the B cell. This is why I am B cell man. Clearly more work on  the B-cell hypothesis is required."

"Once again we need to reflect on the pioneers and heroes responsible for alemtuzumab, in particular Professor Alastair Compston for trying it and Professor Alasdair Coles and his team for their perseverance. Then there is Genzyme who were bold and brave enough to take on the financial risk; the programme could easily have failed. Finally, last but not least, we need to thank the many investigators and MSers who participated in the clinical trial programme. The development of alemtuzumab for MS has been an ultra-marathon."

"The ultra-marathon is not over yet; American MSers don't have access to this drug in their own country and a large proportion of MSologists are reluctant to try alemtuzumab first-line. The latter is the biggest problem; the data is clear that MSers have the most to gain from alemtuzumab when it used as a first-line therapy and as early as possible after the onset of the disease. Alemtuzumab is the drug that under pins the early highly-effective treatment paradigm. Are you ready for alemtuzumab? It is a transformational therapy."



CoI: multiple

21 comments:

  1. Prof G,

    What, roughly, do the other dmts cost annually e.g. Copaxone, Rebif, Gilenya? My friend received Campath in 2004 and 2005 and has had no relapses since the first infusion.

    The cost in today's prices would be £56,000. So spread over the 10 years this equates to £5,600 a year. Not bad value for a return on no relapses and no progression.

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    1. Cost of drugs to the NHS.

      The NHS gets a discount on these drugs; Copaxone = ~£5,200 per annum, Rebif ~£8,300p.a., fingolimod ~£12,800 and natalizumab = £17,600 p.a. + VAT at 20%. All drugs prescribed and dispensed in the community are VAT exempt. All drugs give in hospital have VAT added; hence th £56,000 is actually £67,200. The cost of an infusion is not trivial and comes in close to £650 hence you need to add on another £5,200 and then there is the monthly cost of urine and blood tests. This rapidly escalates above £5,600 per year.

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  2. Profs,

    Availabilty of Alemtuzumab on the NHS is great news and fits with your approach of achieving NEDA. Hopefully, in the next couple of years, some of the highly effective B cell depleting therapies will become available. My question is what does this mean for MS research? With such effective anti-relapse drugs is there a need to contniue research in this area, particularly head to head research c
    Looking at copaxone v rebif. The unmet needs are progression and repair. I'd like to see research focus on these areas. While the future is very bright for those not yet diagnosed with RRMS, we still have huge numbers of MSers who are SP or PPMS, or RRMSers with deficits from relapses. Will research teams make such a shift?

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    1. With regard to studies on existing drugs these are marketing studies that may allow a patent and extension of product life. They may give msers access to a drug that they would not gey access to. In the uk you have the risk sharing scheme. Did it deliver its promise will pharma cough up any refunds. . However eithout that msers in uk wjo have to wait six years for tusabri to arrive and anither decade for campathto arrive.

      However with a kill rate of upto one in five hundred wr must be able to get safer treatments and so.immunology is still being studied. Howevrr things have changed the ms society has funded very little basic immunology for the past years and we switched away from immunology and relapsing disease towards progression over a decade ago and the results of some of these studies are surfacing. So people do change.

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  3. Firstly, big congratulations to Don Giovannoni and his posse for getting Campath 1-H from the bench side to the bed side here in England. One supposes your call to arms encouraging readers of your blog to mobilise and campaign has paid big dividends. You’ve achieved something pretty impressive here. Well done.

    It’s at moments like this, however, one is reminded of Prince Andrei’s character in War and Peace saying: “what is this fantasy that medicine has ever cured anybody ... killed yes!” Leo Tolstoy was right about so much, and his understanding of people’s desire to jump on pharmacological bandwagons because of doctors’ encouragement is probably more valid now than it was almost two hundred years ago when he said it. Illness makes people and those around them desperate; that’s where Big Pharma arrives with talons out and prey in sight. Perhaps you’ve all unleashed a lion instead of merciful lambs. Maybe the arrival of Lemtrada is going to cause irreparable problems.

    One of your readers requested we watch Louis Theroux's documentary on end of life care in LA, which I subsequently did. Young ill people will subjugate themselves to the most aggressive medicines and treatments principally because they were too unwilling to accept the alternatives. These medicines, as one doctor suggested, may have actually ended their life marginally prematurely than what may have been. Drugs give hope, and hope can be, at times, a very delusional thing when sold misguidedly.

    A part of me feels that this blog’s approach in getting alemtuzumab licensed has been the equivalent of the way M&S sells us the idea of having the perfect Christmas: you’ve heightened the fantasy over reality. Come the New Year will we be facing large debt bills and spousal divorce papers once the reality of this fantasy manifests? Who knows, hey?

    So here we are, MSers buoyed on and Sanofi popping expensive bottles of Champaign on a job well done in getting the NHS to agree on paying mega money for an industrial supply of a seriously dangerous drug. Cue the onslaught of Graves’ disease cases, PML, thyroid complications and sundry serious side-effects that may cause more problems than it’s worth. Cue post code lottery realities and reluctant neurologists not wanting to administer the risks that come with this drug. Cue devastated MSers who despite being treated with the miracle of Lemtrada still slide into progressive debilitation only to be told they were too late in getting it. Cue the start of reality biting.

    The real work starts now, Don Giovannoni. Let’s see how this goes. We’re all watching, friend.

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    1. Do we have a safe and efficient alternative? Am I missed something?

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    2. Yes i think so, you have to say safer not safe

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    3. Dr Dre!

      "To say ... (his) ... speech was long-winded would be to utter an understatement as unequaled as his pontification was protracted."

      - long-winded
      - wearisomely verbose
      - tiresomely long
      - talking or writing at tedious length
      - using or containing too many words
      - rambling
      - prolonged
      - tedious
      - wordy
      - long-drawn-out
      - repetitious
      - verbose
      - prolix
      - windy

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    4. Dre speaks sense. Just because he questions the status quo people get nasty. He makes his point more impactful than anyone else here. Thank god for Dre, I say

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    5. Dr. Dre is the man! His ability to so eloquently get his controversial points across makes this blog worthwhile. He makes m e think about stuff in a different way and he seems pretty fair in his criticisms We fear intelligence in our society nowadays. Dr. Dre is obviously very clever.

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    6. (This is Anonymous 8:09:00 pm again)
      "Don Giovannoni and his posse" is nastier than my thesaurus copy-paste

      My comment wasn't about what Dre says, just how he says it. I wish he would make his point in fewer words and spare us these long essays

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    7. Anon 8:55am, I can't believe I'm doing this but I kind of think Dre has a point.

      The argument is that alatuzamab does seem risky. Prof G even admits in the above post that he doesn't fully know how the drug is working - he merely has theories. Considering the possible serious side effects and unknown quantities, more caution seems very logical.

      Dre's prose is flowery and pretentious, I agree. He probably wants to make his arguments register and have greater meaning. It's admirable but requires too many precious brain cells to fully engage with. That is a problem when our grey matter is at a premium.

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    8. I think Dre's essays are entertaining. He makes an effort. We're getting too used to snappy sound bites and Twitter word restrictions. I like it when people write well and can engage at length. It's a dying art form. I like it when Prof G writes long essays, too.

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    9. Dre is the Man....are you sure?

      My little Cousin was in same the English class with Lexie and she thought that Dre must therefore be the girl who used to cry when the teacher caught them talking rubbish:-)

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    10. On a more serious note there an many questions that we do not have answers to. What are the long term outcomes of using Lemtrada...Cambridge has more data than anyone and Dr Coles is talking tomorrow on the "Lessons on the long-term alemtuzumab treatment what we know and what we don't know".

      What do you want to know?.

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  4. If you want to help American ms patients, facilitate medical tourism for rituximab and alemtuzumab.

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    1. Although Alemtuzumab is licenced in canada and mexico,remember you need the monthly check up as if ITP occurs it needs to be dealt with immediately.

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    2. No doubt, but such follow up can be managed. A neurologist could screen for a local doctor willing to commit to after care. Getting around the licensing issue is more difficult.

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  5. "Reluctant neurologists not wanting to administer the risks that come with this drug"

    I suspect this will be correct...so who should chose you or your neurologist?

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  6. Prof G. if you are convinced the B-cell should be the target of therapies would you say that Rituximab is the most promising candidate?

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  7. Re; "Prof G. if you are convinced the B-cell should be the target of therapies would you say that Rituximab is the most promising candidate?"

    Rituximab is not in phase 3; I would say ocrelizumab (Roche) and ofatumumab (GSK).

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