Alemtuzumab use put on Restriction

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The European Medicines Agency (EMA) has started a review of alemtuzumab following recet reoports of sde effects affecting the heart, blood vessels, liver and immune system.  These side effects are rare but potentially serious.

As a temporary measure while the review is being carried out, the EMA has advised that alemtuzumab should only be started in people with relapsing remitting MS that continues to be very active despite taking at least two disease modifing drugs or where other DMDs cannot be taken. So it moves from first line to third line. Those in the US will be saying I told you so as it was placed as a third line drug.

If you have already started Lemtrada and are due to receive further infusions, you should continue with treatment.  Anyone who has been treated with alemtuzumab should continue to have monthly blood and urine tests for four years after the last treatment course

In addition to the restriction, EMA’s safety committee (PRAC) has recommended an update of the product information for Lemtrada to inform patients and healthcare professionals about cases of:

  • immune-mediated conditions, including autoimmune hepatitis (with damage to the liver) and haemophagocytic lymphohistiocytosis (overactivation of the immune system which may affect different parts of the body);
  • problems with the heart and blood vessels occurring within 1–3 days of receiving the medicine, including bleeding in the lungs, heart attack, stroke, cervicocephalic arterial dissection (tears in the lining of the arteries in the head and neck);
  • severe neutropenia (low levels of neutrophils, a type of white blood cell that fights infections).

So Mr Angry will be on my case for being the bearer of this bad news and for contributing to the change in the label (Neutrophils and the anti-drug response). However, this is one reason why you have a Phase IV period where you collect data on the rare side effcts. This has been a story that has just kept giving of recent time as more and more unusual autoimmunities have appeared as case reports. Whilst the thyroid problems were dismissed as treatable others have been significantly more serious.

  • New cases of side effects have been reported with alemtuzumab, including some affecting the heart, blood vessels, lungs and liver.
  • You should get medical help immediately if you experience symptoms of:
    • acute (sudden) heart problems (usually within 1–3 days of receiving the medicine): such as trouble breathing and chest pain
    • bleeding in lungs: such as trouble breathing and coughing up blood
    • stroke and tears in blood vessels supplying the brain: such as drooping of the face, sudden severe headache, weakness on one side, difficulty with speech or neck pain (Really? you have a stroke and you are not going to seek medical help?)
    • liver problems: such as yellow skin or eyes, dark urine, and bleeding or bruising more easily than normal
    • an inflammatory condition known as haemophagocytic lymphohistiocytosis: such as fever, swollen glands, bruising and skin rash.

It is perhaps such a shame that we (ProfG & I) were dismissed over five or six years ago when we when to Boston with a proposal to try and attack the autoimmune problem. There was no enough interest at the time (maybe our ideas were considered to be rubbish) and my ideas of the autoimmunity were Pooh Poohed. The problem now, is that there are alternatives and it will be difficult to recruit…so a window of opportunity was missed. This is rater ironic as it was suggested there was a window of oppertunity to use the drug to work in early relapsing verses progressive MS. Had this been ignored and the right trial-design being used alemtuzumab or more likely the “son of alemtuzumab” would probably have been availablle for progressive MS years before ocelizumab got there..

Now is an oppertunity to work out why alemtuzumab works so well but causes all the problems it does.

So I say thanks very much for the rebuttals, it brought out the ferret (teeth lock when they bite and so don’t let go) in me and the brought out “Le penseur”and has been the giver for a few papers and a lot of student projects, with more to come:-).

The Thinker

So who will be on the PRAC? What will they be looking at?, with Brexit on the cards, Is that a reason I’ve been ignored :-(. I know some questions, I would be asking.

Maybe ProfG (or an alter ego) will come out to give a neuros take on the issue.. as he will have more inside knwledge

About the author

MouseDoctor

29 comments

  • We need to remember that it’s neuro scientists and researchers who come up with the ideas for treatments. When you look at the highly effective treatments, they all have some serious side effects.

    Alemtuzumab remains one of the most effective treatments for MS. Most of the side effects can be picked up by monitoring and treated effectively. My MS is inactive 12 years after my first round of infusions. Prof G has proposed that for some it could be a cure (15 year treatment).

    It’s easy to stick the side effects on the box, but what about the side effects of not taking a highly effective treatment. The PM’s mother died in her early 50s, J K Rowling’s mother died in her mid-40s, Jacqueline du Pre died in her early 40s. MSers die c.7-10 years below the average life expectancy and need substantial care well as MS advances. Prof G refers to MS as a dementing disease and says that cognitive issues are as bad (if not worse) than the physical issues. My GP visits three women in their 30s with MS who are in elderly care accommodation. MS leads to unemployment, break-up of relationships, suicide (particularly in men) etc etc. These are the real side effects of MS and in my view the side effects of Alemtuzumab must be balanced against them.

    Having Alemtuzumab as a third line treatment means that patients will still be loosing brain as the first and second line treatment are pretty ineffective.

    I would have gladly taken the 1-3% risk of death with HSCT if it had been available. MS at the latter stages is worse that death (Prof G posted something on his Twitter account yesterday about a man who is paralysed from the neck down because of MS).

    I hope that Alemtuzumab will come back as a first line treatment for those who understand the risks and are prepared to accept them (against the real risks of MS).

    I hope this blog doesn’t gloat too much with the usual “we could see it coming”, “we could have sorted it out if they’d let us”. The real losers are MSers again.

    In the meantime MSers who were looking at Alemtuzumab my have to consider Nataluzimab (and the PML risk) or Ocreluzimab (big questions as to whether it stops patients moving to progressive MS).

    The one thing I’ve learned about MS research over the last 18 years (since diagnosis) is that you build us up to knock us down. We still wait for the neuro-protectants, re-myelination therapies and neuro -restorative treatments). What the researchers have given us are a choice between fairly ineffective treatments with few side effects or highly effective treatments with more side effects (sometimes serious). We are caught between a rock and a hard place.

    Sad day.

    • “It’s easy to stick the side effects on the box, but what about the side effects of not taking a highly effective treatment.*

      Extremely well put. I wish that all neuros could take their patients down this line of thinking when helping them to make the best choice of drug.

      Instead, many pwMS are left with the feeling that in this scary new uncertain world they are in that the choice between terrifying sounding drugs has been left to them.

    • Excellent words. Thank you for expressing what I cannot due to being devastated that I now cannot go ahead w my first lemtrada round in a few weeks.

    • “Sad day…”

      Yes..now you join u.s. where it’s not
      really prescribed.
      One option would be book travel to Russia,India,Mexico
      for HSTC.

    • Did you only have one round of alem infusions in total to date?
      As in the infusions on five consecutive days, as an inpatient and no round two a year later?

      • I had two rounds (5 days first year and a year later 3 days). I did get thyroid issues and now take a pill a day. I’ve had 12.5 years relapse free (and my relapses before Alemtuzumab were very disabling) with no further treatments. My EDSS is stable. I’m not saying the risks should be dismissed and are not for everyone. It’s been excellent for me and I’d do it all again if required. My neuro is excellent as is the MS clinic. They are thorough with the monitoring / follow-up.

        Correction to my first post – Prof G proposed that the question as to whether Alemtuzumab was a cure (for some) is a 15-20 year experiment.

  • Thanks . Out of interest are there any pwMS who have had only one round of alemtuzumab and are doing well. And have not taken another DMT ?
    In other words could one round of alemtuzumab and no futher DMT be enough in some cases?

    • Came across this awhile ago; it’s a small group, but as they say, warrants further study.
      https://www.ncbi.nlm.nih.gov/pubmed/29666985

      Induction of disease remission with one cycle of alemtuzumab in relapsing-remitting MS.

      “CONCLUSIONS:
      Given that 96% of patients who did not relapse in the first 12 months following the initial dose of alemtuzumab remained relapse-free regardless of receiving a second course of drug, our data suggests that induction of disease remission for some patients might occur following just one dose of alemtuzumab. With further study, these data could support modification of the current therapy regimen.”

      • Thanks for this. I’ve had one round and have a few concerns about having round two. So this is assuring in some ways.

        • I wonder if it would be possible to have round two of alem if I start relapsing sometime after 12 months, rather than booked in for 12 months after round one ?

          Do you think this might be an option?

  • You were promoting Alemtuzumab for PPMS + everything else on the ‘pyramid’ as and when it becomes available? This is not realistic I think. I hope the problems with Alemtuzumab are more fuel to whichever research engines there are looking for safer treatments, looking for the cause, the antiviral…

    Look what has been done for cervical cancer rates with vaccination! That’s real progress.

  • Since Taking My 2nd course of Alemtuzumab. My BP has been a little funny. My diastolic is 110 whilst my stiaslotic is 133. Could this be a clotting issue caused by Alemtuzumab? If so how can I have this investigated?

  • What happened to Prof G post? How was Prof G promoting himself other than giving his expert advice. The blog does not look or feel right. It’s lost its soul.

  • 3/ Net Sales by Franchise
    The table below sets forth our 2016 net sales by franchise in order to facilitate comparisons with our peers. For a detailed reconciliation of net sales by franchise and net sales by GBU for our Pharmaceuticals segment, refer to the table showing Pharmaceuticals segment net sales by geographical region.

    (€ million) 2016 2015 Change Change constant For/exchange

    Multiple Sclerosis 1,720 1,114 +54.4% +56.1%
    (total

    Aubagio® 1,295 871 + 48.7% +49.7%

    Lemtrada® 425 243 +74.9% +79.0%

    Total
    Multiple sclerosis
    1,720 1,114 +54.4% +56.1%

    UNITED STATES
    SECURITIES AND EXCHANGE COMMISSION
    Washington, D.C. 20549
    FORM 20-F

    Sanofi

    There goes the botom lin€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€

    https://www.sanofi.com/-/media/Project/One-Sanofi-Web/Websites/Global/Sanofi-COM/Home/en/investors/docs/0000-2999/20-F_2016.pdf?la=en&hash=7846BE2C0A1CB7D9EB60A24C8274D5DE2D43CFDA

    Obrigado

  • Really well put Mr Angry!
    Am feeling a lot of hurt at the moment for Bonnielle and all the others who are experiencing the devastation of having their receiving Lemtrada cancelled. I recall the impact of having my hospital admission delayed by just a couple of days and the thought of so many having to deal with Lemtrada treatment being cancelled completely is really awful!

    Additionally I’m saddened by the impact on this Blog of ProfG no longer being a main player in terms of provision of posts and replies to the resulting comments, and as a more minor point, the fact that he’s no longer supposed to use ‘ProfG’ It’s silly maybe to feel the loss of an online form of personal identification, but it feels that way for me – yes, you can read his response on Medium, but he’s been a lynchpin, alongside MD on THIS blog!

    I’ve devoured this Blog on a daily basis since being diagnosed 3 years ago and have been totally persuaded by the argument for ‘flipping the pyramid’ – ending use of CRABS etc. So, does this development with Lemtrada mean another loss in terms of the prospect of ever seeing an end to the use of the escalation treatment model?

    Very sad right now😔

  • Does anyone know how these regulation changes in the UK will affect access to alemtuzumab in other countries? Namely Canada? Any Canadians with their finger on the pulse regarding Lemtrada?

    • ” I saw a patient for a third opinion late last year. She was in her mid-20s and had just failed alemtuzumab with a severe spinal cord relapse 19 months into her 2-year alemtuzumab treatment”

      It’s great for what it is..but this is a reminder..It’s not a cure for everybody.

  • How flexible is it to have the Lemtrada second round?

    Is it only 12 months after the first round or can it be 18 or 24 months after round one?

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