Maven has Landed on the other side of the pond

M

Thanks FDA….you made our REF2021 impact statement even better!!!!…… Only joking.. but today signals a new chapter in our journey with cladribine.

The MDs became CLAD lads way back in December 2004, when we did our first experiment with cladribine.

We saw the potential of the intravenous and subcutaneous variant in MS and had spotted that we could develop an oral variant, if we could have got it off the shelf in Boston (Probably parked so it wouldn’t complete with alemtuzumab).

As to our experiment with cladribine in Mice…..It’s didn’t work :-(.

I presented the daaaata (a clue here is where it was presented:-) for the first time and only yesterday . But hey ho who cares if it is not an EAE “cure of the week”. It’s all biology and mice have the wrong biology

Makes a change that it wasn’t “cure of the week” from animal experiments

But little did we know that ProfG was secretly working with the the oral cladrine tablet team to aquire the rights to develop a new oral variant of cladribine, where the patent was filed in 2004.

ProfG was intimately involved with the development of the first trial of oral cladribine tablets. Dr M&M treated our first person with oral cladribine. This was published in 2010.

Sadly in 2011 the FDA put a spanner in the works and they wanted more trial data. The company spat the dummy (an Australian term) and refused to do it and a bit like a spoilt kid…cut off their nose to spite their face.

They were before their time…a treatment effect with a long-term efficacy off a short-term treatment. It worked by depleting lymphocytes. The FDA didn’t get it, that it was a mechansim of action and not a side effect.

In the rush to do the studies, they had forgotten to do a second trial and a safety signal spoiled the party

Amazingly the European Mediciens Agency still don’t get it as they made the similar comments when oral cladribine was approved in europe in 2017.

Anyway MD and DrK picked up the pieces realising that the men in grey suits (actually that’s neuros in UK, in Australia apparently it’s the men in Beige and the US it’s men in blue blazers, beige chinos and histoically loafers…no joke but now it’s clunky running shoes or two tone comedy shoes…you think I’m joking…Go to a meeting in the US:-)

DrK and his team realised that the safety signal was probably a fluke. The FDA wanted more information from the European company, but seemed happy to ignore an even greater signal from an American -made drug:-(.

Anyway today the Food and Drug Association has seen sense and has today approved cladribine tablets for the treatement of MS. This is approved for relapsing and secondary progressive MS.

So two treatments for our American Friends in one Week.

So in a nutshell

Could I say it in a sound bite?

A new agent that gives selective reduction, replacement and resetting of the imune response to target a core disease biology of relapsing (and progressive) MS…A platform for neuroprotection and repair that give long term effect from a short term treatment

P.S. Cladribine tablets has yet to be shown to work in progressive MS, but the biolgy tells me what will happen…..

COI: Multiple but am currently presenting at a meeting

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MouseDoctor

9 comments

  • Congratulations!!!!
    It is a shame mice are so “important”. So many times it works in mice and not in humans.
    As for Cladribine i personally think it is a good drug for spms. After 10 months on it it has slowed degeneration way a lot comparing how fast i was going down with “wonderful” fingooimod. Fingers cross the good effects remain.

  • Great effort again DrK, Prof G and the MDs.

    “It worked by depleting lymphocytes”

    I am a bit confused here as to the mechanism of action with regards to Lymphocyte count. Tysabri has been shown to induce benign lymphocytosis (https://tinyurl.com/y2ca4drd). Some have even speculated of using Lymph. count as a biomarker proxy (https://tinyurl.com/y24f272h).

    How does tie up with the cladribine’s depletion?

    Thanks again,

    Tony

  • Why are you so sure that cladribine will work for progressive MS?

    and if you do think it will work does that mean you think it will work better for progressive than it does for rrms?

    • Of course it will in progressive MS, because RRMS and progressive Ms are the same disease. Will it stop worsening highly unlikely because there are elements of progressive MS that are unresponsive to this type of drug. As baselayer for other things

      • So surely any trial for a drug in progressive MS needs other protective drugs used in conjunction because a drug on its own as you have said will not yield positive results and so is surely a bit pointless

        Furthermore the drugs used for progressive MS in conjunction with other protective or remyelination drugs should be the most effective currently available drugs used for relapsing-remitting eg alemtuzumab

  • Cladribine does not work for progressive MS until it is proven to work for progressive MS.

    Saying anything else is laying speculation upon incomplete knowledge of the pathology of progressive MS.

  • So for Cladribine to be a long term treatment solution, what happens after the EMA approved two treatment cycles are over?

    Can the treating neurologist simply recommend further treatment cycles in case lymphocyte counts have returned to normal? If so, are there any long term studies to back this approach? Would the cost of a third cycle even be covered?

  • Congrats! After all the trials and tribulations this must feel like a great outcome!
    Onwards and upwards I hope for those with SPMS who’ll benefit and ditto with ASAP attached for Progressive MS.
    Is it a well deserved beer or glass of vino this weekend🙂

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