Subcutaneous Cladribine as a Treatment Option

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After Cladribine tablets had been rejected by regulators in 2010/11, Merck-Serono binned their respective development programme. This was in spite of excellent data on disease control and adverse events – if there hadn’t been those three cancers in the active arm of the CLARITY study (and none in the placebo arm). Although it subsequently turned out the malignancy risk with cladribine is no different than with other highly effective DMTs (in fact, more recent data suggest cladribine is at the lower end of the risk spectrum), the reputational damage was done, and the mud stuck firmly, indeed in some of my fellow neurologists’ minds it’s gotten stuck to the present day…

However, we looked at the data and saw huge opportunity, not primarily to help Merck recover from throwing the baby out with the bathwater, but to help people with MS in the UK and worldwide getting access to an effective drug that’s been sitting on the shelf for decades (licensed for hairy cell leukaemia), if only in a less convenient formulation than a tablet, namely as an injection.

Hence, from late 2014, we started using subcutaneously injected cladribine to treat pwMS who were either not eligible for NHS-funded DMTs or chose the compound over what was on offer at the time. Should you wish to revisit the early history of how this all came about, eventually leading to a collaboration with Merck that now (alongside the MS Society UK, National US MS Society, Barts Charity and – in particular – the NIHR) delivers #ChariotMS , click here and read MD’s White Knight Diaries.

Following peer review, our manuscript was accepted last Friday, the final day of #ECTRIMS2021. In it, we report our experience with subcutaneous cladribine in pwMS, an attempt at making a difference irrespective of NHS-DMT eligibility. The long list of authors illustrates broad support of this approach by colleagues with an interest in MS across the UK, and beyond.

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The abstract (full paper upload to follow) speaks for itself – subcutaneous cladribine is a promising option for pwMS across the disease spectrum who display disease activity based on either MRI and/or through elevated CSF neurofilament levels.

Among others, we hope this might help underpin the MS International Foundation’s (@MSIntFederation) drive towards improving access to effective immunotherapy in lower and middle income healthcare environments. The willingness of pwMS to undergo the treatment with BartsMS as well as our positive, albeit preliminary, outcomes were key factors in getting #ChariotMS underway. Thanks for all your courage and support !

@KlausSchmierer

CoI: I am the Chief investigator of ChariotMS, which is co-funded by Merck. I also serve on the steering committees of Merck’s MAGNIFY-MS trial, MS Masters Forum, MS Global Advisory network and ‘MS in the 21. century’. Lipomed supported an early ChariotMS investigator meeting in July 2017.

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6 comments

  • I don’t understand why would someone choose a subcutaneous injection given that cladribine is availble as oral tablets.

    • To do with licensing. Back in 2014, tablets weren’t available, they were only approved in August 2017 in Europe, and in 2019 in the US. Depending on the healthcare system you live in, there are restrictions/eligibility criteria for accessing the tablets which are largely based on cost-effectiveness.

      • Unless the patient is needle-phobic, do cladribine tablets have any advantage over subcutaneous cladribine?

        What treatment protocol and dosing do you follow for subcutaneous cladribine?

        • Advantages of the tablets are (i) placebo-controlled trial data, (ii) ongoing systematic research & pharmacovigilance, (iii) no need to visit the centre since pills can be taken at home (particularly useful in a pandemic and for people with difficulties mobilising), (iv) support for service, teaching, training.
          I just proof-red the manuscript and expect it to be available online shortly. I’ll put a note here on the blog once that happens; won’t be long and available open access. The dosing schedule is part of it there.

  • Prof K,

    I appreciate your determination.

    Are the results from subcutaneous cladribine and tablet form cladribine exactly the same? I thought a drug would be more potent as subcutaneous.

    Did subcutaneous cladribine show any impact on oligo clonal bands?

    • The active ingredient in both variants are the same.. However sSubcutaneous cladribine is 100% bioavailable meaning what you inject enters the circulation to have a potential impact. Oral cladribine is about 40% bioavailable, so to get the effect of a 10mg tablet you have to inject about 4-5g of subcutaneous cladribine. In the subcutaneous cladribine studies dose equivalents were used to replicate the approved oral dosing…so that the safety profile would be similar, but with the subcutaneous dosing it was more dose adapted to make it potentially safer to limit marked lymphopenia.

      The oligoclonal bands studies are ongoing I believe…I have made my predictions and we aim to back these up with science and biology

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