Tuesday, 12 January 2016

Shaken or stirred: How would you like your Cladribine?








25 years ago this team of oncologists from the Karolinska University Hospital in Stockholm showed that Cladribine can not only be given as infusion but also as an injection under the skin, or administered as a drink. When taken orally the dose had to be doubled, but the figure below indicates the stunning similarity between all routes of administration in terms of plasma concentration.



Since Merck Serono took over development of oral Cladribine (Movectro), this route of administration cannot be used without infringing their patent.

However remember, only 6 (six) subcutaneous injections (10mg/vial) are required in a year to achieve a dose equivalent to the one successfully used when oral Cladribine was tested in CLARITYand ORACLE MS.

If Movectro gets a license from the EMA, and the annual course of treatment costs say £25,000, would you be prepared to have six injections* instead of generic Cladribine, for example Litak, costing less than £1,000?

This is a serious question.

*No injection site reactions such as those known from beta-interferons. 

MD says "It is amazing that Merck spent a estimated $800,000,000 according to a financial website (so it could be untrue) to develop the pill version". So enough to treat about a third of the World's population of people with MS".

17 comments:

  1. I live in the UAE where my access to medication is tied to my work provided health insurance hence I feel like I'm tied to a job I HATE.I wish that I could switch to generic Cladribine to regain my freedom !!

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    1. Move to the UK. Life is good here, as are employment laws.

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  2. It's a no brainer! Just 6 subcutaneous injections for less than a grand? Just think how many people could be treated! Do Merck really believe we're that wimpy about injections?! And I who injected their stingy acidy Rebif three times a week for five years!

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    1. Thanks, we'll survey this, but your response is certainly a great start!

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    2. Klausy, excuse the French but Can I take it in my ass?

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    3. Oops I messed up there: 1 cx Copaxone which costs about R$ 4.000,00 amount to almost £700.00. In any event the amount spent here with 2, 3 months of treatment with Copaxone pay the Aníbal costs of Cladribine ...

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    4. I will not make a joke form your comment but the injection is subcutaneous not intramusclular so as long as you can pinch some skin to get underneath it with the needle the skies the limit, but we will be providing you with the details of what would be involved in the next couple of days. People used to taking beta interferon it would be a sinch.

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    5. Anon 6:43 - one could argue that Team Mouse are trying to prevent you from 'taking it in the rear' from big Pharma, by getting you knowledge, and access to generic Clad treatment at just a fraction of the cost that Pharma would try to. :)

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  3. I don't think it's a matter of them thinking we're wimpy. I think it's simply a matter of them valuing their portfolio and their shareholders more than the health and well-being of human beings in need.

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  4. ...Even though NEDA in Copaxone in almost 02 years, I change in the moment for generic Cladribine without hesitation! I don't want to wait MS reappear in me with all its fury, and I see the Cladribine as the best options at the time, probably is the best.
    I may not have many side effects with Copaxone, but I know that the efficiency is very low, out having to inject all the day; it is not so much the act of injecting itself but has no adipose tissue that can withstand it for so long.
    Off the cost issue. A monthly Copaxone box with 28 injections goes for about R$ 4.000 (£ 23.560) to the Brazilian Ministry of Health.
    Look at the economy it would be with Cladribine injectable generic!!
    Two months of Copaxone would pay nearly all expenses of the annual treatment with Cladribine!!! Very good is that o//

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    1. Here's a good paper comparing Azathioprine to Clabridine:

      http://www.ncbi.nlm.nih.gov/pubmed/20567960

      Most likely this post will be removed by Team G or the author will be bashed.

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    2. So it sounds like you have been trawling to find a paper to counter the value of Cladribine.

      Cladribin-Tabletten bei schubförmiger Multipler Sklerose
      Noch ein Purinanalogon oder echte therapeutische Innovation?
      S. Schmidt. Nervenarzt. 2010 Oct;81(10):1231-41. doi: 10.1007/s00115-010-3040-6

      However as the article is in German I am not going to comment on it as it will take me a while to read as my German vocabulary with not be good enough, however maybe DrK may have a flick through it. We can deal with alot of different European languages within the group.

      Azaothiaprine is anti proliferative cell and was recently shown to inhibit the rate of relapse to about the level found with beta interferon, so way less than expected for Clad

      http://multiple-sclerosis-research.blogspot.com/2014/11/cheap-as-chips-azathioprine-is-better.html

      It is also not an induction therapy

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    3. Why remove it - because it's in German? – Nothing disagreeable with that:

      “Für AZA konnten konsistente Effekte auf Schubratenreduktion und EDSS Progression überwiegend durch Metaanalysen gezeigt werden. Prospektive, im Rahmen von Phase-III-Studien erhobene Daten zu MR-tomographischen Endpunkten existieren nicht. Darüber hinaus wird die Bewertung der Studiendaten durch den Einschluss heterogener Studienpopulationen sehr erschwert.

      Im Gegensatz dazu konnte für parenterales Cladribin und Cladribin-Tabletten eine hoch signifikante Schubratenreduktion sowie eine Reduktion T1-Gd anreichernder und neuer T2-Läsionen in mehreren Phase-II- und III-Studien gezeigt werden. Darüber hinaus konnte ein Effekt auf die EDSS-Progression bei RRMS mit Cladribin-Tabletten nachgewiesen werden.”

      Which can be interpreted as: There is evidence for an effect on relapse reduction on Azathioprine, however mainly through meta-analyses (the paper by Luca Massacesi, et al. was only published in 2014 – we discussed the study: http://multiple-sclerosis-research.blogspot.com/2014/11/cheap-as-chips-azathioprine-is-better.html), without underpinning MRI data, and in quite heterogeneous study populations.

      For Cladribine (specifically highlighting parenteral and oral formulations!) a highly significant reduction in relapse rate, as well as reduction in T2 and Gd-enhancing T1 lesions and a significant effect on EDSS were shown.

      Over and above the fact Azathioprine is not an induction treatment, and has a relatively modest efficacy in pwMS, it is quite often not very well tolerated (we use it in autoimmune conditions, for example, myasthenia gravis).

      Delete
  5. Shaken or stirred? I'll take my Cladribine with a "Bond girl" thank you.

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  6. I think I remember Prof. G. saying something about Cladribine *permanently* depressing the immune system after induction is completed, though not by all that much. Did I understand that right? If so, that's a bit of a negative. Though obviously preferable to active disease.

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    1. No doubt, and repeated many times on this blog and elsewhere, one cannot rule out an increased long term risk of highly effective immunosuppression. This applies to any drug with which immunosuppressio is achieved, though some have an already established and quite specific high risk, say TRAL in Mitoxantrone.

      For Cladribine, some long term data (20 years follow up) are available on the secondary cancer risk in people who were treated with Drug C for hairy cell leukaemia (HCL). Here's from a series of 88 pwHCL (http://www.bloodjournal.org/content/123/2/177.long?sso-checked=true):

      "Eleven second primary malignancies were documented in 8 (9%)
      of the young HCL patients treated with cladribine, representing a low and statistically insignificant (1.60-fold) increased risk of developing second primary cancers. Four of these second malignancies were hematologic. Earlier reports documented second malignancies in 8% to 22% of HCL patients following cladribine. Using National Cancer Institute SEER data, investigators at Scripps Clinic have previously reported an observed-to-expected ratio of developing a second primary malignancy following cladribine treatment from 1.88 to 2.03, both representing a relatively small but statistically significant increased risk. This is reassuring given the young age of these HCL patients and the initial concerns that cladribine-induced immunosuppression might be associated with the late development of second primary malignancies."

      As you say, it is always the risk-benefit scenario that counts, and where people will make different choices. We are participating in an MS Society-funded study run by Leeds University that is about to start exploring the issues surrounding decision making further.

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  7. its funny that i have control of the spam button yet trolls behave like trolls and end up in the bin

    ReplyDelete

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