Friday, 23 June 2017

#NewsSpeak: another eagle has landed only this time it is a maven

Oral cladribine finally gets licensed for the treatment of relapsing MS #NewsSpeak #MavenClad

I was invited to a meeting to advice Serono in 2002 whether, or not, they should in-license an oral formulation of cladribine. We advised yes and today the CHMP have recommended that the EU give Merck a marketing authorisation for oral cladribine. The process took 15 years. Who said MS drug development was fast? 

The oral formulation of cladribine, Mavenclad, is the first oral selective immune reconstitution therapy (SIRT)* for treating patients with active relapsing MS. 

*Please note SIRT is a new term to describe the class of drugs that work via immune depletion, which can be non-selective or selective, followed by immune reconstitution. 


CoI: multiple  

37 comments:

  1. Replies
    1. Well done ProfG.
      What will angry of Tunbridge think of this?
      Eating humble pie twice in fortnight

      Delete
    2. Suggest he goes on a liquid diet as more to come....On a roll:-)

      Delete
    3. Angry of Tunbridge is happy. It's because of my badgering that Team G finally got their act together and started publishing decent research papers and helping get agents to the patient. So well done Team G. Unlike you Mouse I don't touch alcohol (Devil's brew). Keep up the good work.

      Delete
  2. Big news. Now they should re-introduce it in Australia where it has been licensed for the better part of a decade.

    ReplyDelete
    Replies
    1. I am sure Australia and Russia will be first in the queue

      Delete
    2. Somebody told me Australia is in hand.

      Delete
  3. Well done, but... 15 years??? Really?

    I know it takes long for the clinical trials, but that long is unacceptable.

    ReplyDelete
    Replies
    1. A big reason for the delay was development was stopped in 2011 by Merck Serono because of a cancer risk, which was subsequently identified by Dr K and team as erroneous in 2015 https://www.ncbi.nlm.nih.gov/pubmed/26468472 this led to Movectro's reactivation and resubmission to the EMA and now approval.
      I hope Merck Serono will be showing their appreciation ;-)

      Delete
    2. It shows you how long it takes.

      First they had to work out how to take a drug that is active in MS and turn it into a drug that is active in MS and has a patent attached to it.

      In this case they took generic cladribine that is active via the intravenous or subcutaneous route and spend a few hundred million making it into an oral version so you can take a few pills a year rather than a few 10 second injections.

      Do the toxicology and do a thousand peorson trial. This was done and dusted before 2010.. So then you go on a 7 year holiday urinating money away from lost sales.

      Happy to play a part no matter how little.

      Delete
    3. Who is that person/organization with God's powers who decides that some hundreds/thousands of people will not be on the DMD which may work the best for them for 7 years?

      While there are other DMDs for pwRRMS, a similar story applies to ocrelizumab, where there is no alternative for pwPPMS. The system is broken.

      Let's assume that someone finds the cure for MS next month. Will we have to wait another 15 years till we have access to it? And till that time, are we going to see ourselves lose the ability to walk, hand function, etc etc?

      Delete
    4. The God is called the EMA and it represents its democratically elected member states.

      Delete
  4. This is awesome! So is that paper... My favourite bit, is the bit that says "The authors are grateful to Barts Charity for funding to cover publication costs".
    Have to admit, it is pretty cool to be treated in a healthcare system where our national academics have got 2 excellent treatments licensed to treat this historically intractable condition in less than a decade! Huge thumbs up to British research!

    ReplyDelete
    Replies
    1. Thanks for the support, but the pharma stuff has to thank French (Sanofi) and German (Merck) resource to make it happen

      Delete
    2. But modesty gets you nowhere Dr Mouse. Take the compliment as it was intended.

      Delete
  5. Just got home from a very long day and was reflecting on the EMA's decision and the whole drawn out process of getting Clad to market. I am feeling a bit flat and let down. Why? Mavenclad should have the same license as alemtuzumab, i.e. we should be able to offer it patients with active relapsing-forms of MS.

    I can already see the perverse scenario emerging in which a patient wants an IRT (immune reconstitution therapy) and has active, but not highly active, MS and all that we can offer is alemtuzumab in the class. C'est la vie?

    ReplyDelete
    Replies
    1. Don't feel flat, you did your bit. Well done, there are not many clinicians who have the good fortune to take a drug to market.

      Just think how people at Novartis felt they get a second line licence whilst you got alemtuzumab a first line licence

      Delete
    2. Yeah thinking about it, its all messed up...what where the regulators thinking?

      Delete
    3. Part of it is the old story of the horse turning out to be a camel when a committee designs it. There are motives involved that have nothing to do with the science.

      Delete
    4. Well done Professor G. and the Barts folks.

      Once again you have helped change the world!

      Dont 'feel flat' Prof. G. The world of MS is changing faster and faster thanks to folks like you and yours.

      People thinking of new ways to view MS and more, old guard .vs. new in many ways.

      Let's move it ahead!

      We're gearing as we speak to help.

      Delete
  6. Gavin I note Fred Lublin referred to you last night as an 'inductionist', it sounds much cooler than an SIRTist. The latter sounds like and itch in a place you don't want to discuss ;)

    ***

    P.S. Congratulations and don't be too disappointed, when you take a broader perspective cladribine got there against all the odds. I am looking forward to being able prescribe it myself without having to refer my patients East.

    ReplyDelete
    Replies
    1. Can we think of an appropriate word beginning with D
      apparently PIRT means something bad in German...DrK must have been away to long as he wasn't aware of it.

      Delete
    2. PIRT sounds to similar to PERT that means something sexy in English.

      1. adjective
      If someone describes a young woman as pert, they mean that they like her because she is lively and not afraid to say what she thinks. This use could cause offence.
      ...a pert redhead in uniform.
      ...pert replies by servant girls.
      2. adjective
      If you say that someone has, for example, a pert bottom or nose, you mean that it is quite small and neat, and you think it is attractive.
      [approval]
      But there is more to Charles than his pert bottom and hairy chest.
      ...the tiny drops of rain gleaming on her wide forehead and her pert nose.

      PIRT would never have done it for me. Is a SIRT any better? Possibly.

      Delete
  7. What will this mean for your #OffLabel campaign? Will you stop promoting and using cladribine off label?

    ReplyDelete
    Replies
    1. I want treatment for all, if you are EDSS 6.5 you will still have no option unless one goes off-label. I think todays announce vindicates the stance of DrK that this is not a second rate treatment option

      Delete
    2. However the highly active indication makes no sense if you consider alemtuzumab, could you use off label for low activity...all makes no sense

      Delete
  8. The major side effect is lymphopenia....how bonkers is this, the drug kills lymphocytes as mechanism of action and its a side effect.

    ReplyDelete
  9. What is difference between active and highly active? They mention imaging, are there a different number of active sites?

    ReplyDelete
    Replies
    1. I dont know i will let G answer.
      The difference.... a few thousand pounds...they will charge more for a second line than they would had it been first line and greater sales i suspect. It is in the space of natalizumab

      Delete
  10. maven
    ˈmeɪv(ə)n
    noun NORTH AMERICAN informal
    an expert or connoisseur.
    "fashion mavens call beige oatmeal"

    Is Cladrabine called a MAVEN because it does something different?

    ReplyDelete
    Replies
    1. Maven actually comes from Yiddish, but it has made its way into American slang.

      Delete
  11. Nice work...But how mu$ch will it co$t....?

    Luis

    ReplyDelete
  12. Good News!!

    Finally the eagle will fly.

    Lymphopenia but no risk of PML, right ?!

    ReplyDelete
    Replies
    1. There is a long history of cladribine use in hairy cell leucemia and this is not an issue, but never say never. Cladribine does not seem to deplete CD8 cells much. Using a dose adapted approach based on lymphocyte numbers we don't have grade 3/4 lmyphopenia.

      Delete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.