Sunday, 18 September 2016

The Vikings started it..will they end it

We have the Viking hypothesis that MS started in the Viking nations and then the British Distributed MS around the World. As ECTRIMS in Britain comes to a close, perhaps the Vikings are starting the end of company interest in Immune DMT in MS.

There are now well over ten DMT, with each new addition costing more than the last. 

The next in line is probably ocrelizumab, which is an anti-CD20 B cell depleting monoclonal antibody. This looks set to sweep some of the current DMT under the table…but is it?


The MS bubble is set to burst by 2019 as fingolimod comes off patent and the introduction of generic fingo should see prices tumble. That is unless pharma has something up its sleeve. The major generic makers are also the people making MS DMT, which could through a spanner in the works. This could mean few, if any new drugs to treat relapsing MS, because the costs of the trials to show incremental benefit above what's there now will mean big pharma will be off to find rich pickings elsewhere.

However are the Swedes hastening this downfall? 

The high cost of drugs appears to be all well and dandy in the USA, but it means that low and middle income can't get access to drugs because of cost. In Europe, where there is socialized medicine the costs put strains on the National Purses and this limits access to treatments. 

If we consider those with high cost, such agents can be rationed. However it is clear that there are generic drugs that could be efficacious and more cost-effective. Can they be used, well according to the Health minister, Doctors have the right to prescribe off-label and in certain parts of Sweden Off-label accounts for about 90% of the MS drug use.

There is no doubt in my mind that anti-CD20 inhibits relapsing MS and also it appears to inhibit active progressive disease at least. 

Ocrelizumab is a humanised anti-CD20 at the regulators at the moment. Ofatumumab is a human anti CD20- B cell depletor and is in phase III trial. 

However there is a chimeric antibody antibody available called Rituximab, which is a chimeric part mouse part human antibody and the Swedes have been using it...... a lot, yep I mean a lot

165 - Rituximab in multiple sclerosis; data from the swedish MS registry
P. Alping1, A. Svenningsson2, J. Salzer3, J. Burman4, C. Dahle5, K. Fink1, J. Hillert1, J. Lycke6, A.-M. Landtblom4, C. Martin2, P. Nilsson7, F. Walentin8, T. Olsson1, T. Frisell9F. Piehl11Clinical neuroscience, 2Clinical Science Danderyd´s Hospital, Karolinska Institutet, Stockholm,3Pharmacology and Clinical Neuroscience, Umeå University, Umeå, 4Neuroscience, Uppsala University, Uppsala, 5Clinical and Experimental Medicine, Linköping University, Linköpin,6Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg,7Neurology, Lund University, Lund, 8Neurology, Örebro University Hospital, Örebro,9Medicine Solna, Karolinska Institutet, Stockholm, SwedenBackground: Rituximab (RTX) is a monoclonal anti-CD20 B-cell depleting antibody. Two smaller randomized studies in MS have shown promising effects of RTX, both in relapsing-remitting MS (RRMS) and in primary progressive MS (PPMS). Furthermore, in an observational study we recently found that disease reactivation after terminating natalizumab due to positive JC-virus serology was much lower for RTX compared with fingolimod (Alping et al., Ann Neurol 2016 PMID: 27038238). In Sweden the off-label use of RTX for MS, especially in JCV+ RRMS and inflammatory active progressive MS, has increased rapidly over the last years. 
Objective: To describe and compare baseline characteristics and outcomes for patients starting RTX, FGL, or NTZ therapy, for MS, in Sweden, using data from the Swedish MS register (SMSreg). 
Methods: Baseline and follow up data on all patients treated with RTX, FGL, and NTZ were retrieved from the SMSreg.
Results: In our preliminary data set, we identified 2041 MS patients treated with RTX (until 1 Dec 2015). These patients correspond to 25.3% of all patients with disease modulatory treatment, or 14.9% of all active MS patients in SMSreg. The mean age was 43.6 years, 68.9% were female, and the listed disease course was 68.4% RRMS, 23.6% secondary progressive MS (SPMS) and 6.1% PPMS. The mean disease duration was 11.3 years and the mean treatment duration 21.1 months. At start of therapy the mean expanded disability status scale (EDSS) was 3.22, symbol digit modalities test (SDMT) 50.8, multiple sclerosis impact scale-29 (MSIS) 1.94 (physical) and 2.30 (psychological), respectively. The proportion of patients who terminated RTX therapy for all reasons was 9.3%. Additional data on effects over time on EDSS, SDMT and MSIS-29 will be included in the final presentation, as well as corresponding data for the FGL and NTZ cohorts. 
Conclusions: We here report the largest cohort of MS patients treated with RTX over an extended period of time. Preliminary results indicate that RTX demonstrates a high degree of drug survival, with few treatment interruptions due to an inadequate treatment response or adverse events. Furthermore, we will also present a comparison between RTX, FGL, and NTZ, thus shedding further light on the role RTX in the treatment of MS.

Although this use accounts for only twenty percent of all treatments. In the southern regions this was 10-15% but in the North it was nearly 90%. 

We know that the efficacy rates of anti-CD20 are about the same as anti-CD52, but without the secondary autoimmunities and reported greater efficacy than other DMT so with a cheaper alternative will this be the end of pharma Ker ching?  

Apparently a Pharma company complained about this, but the Swedish Government discussed it and said it was OK to prescribe off label. So if we get spreading of neuro courage it will make it even more difficult for Pharma. Once people realise that Cladribine is just as good a B cell depleter at a quarter of the cost what next.....anarchy. 
 Anyway this is my highlight of ECTRIMS 2016

7 comments:

  1. I am from the US and taking Rituximab. The question I have is when/if Ocrelizumab is approved, why won't care providers choose the cheaper Rituximab? Will neurologists not have this choice since Rituximab isn't approved for MS? Since there are no clinical trials for Rituximab in regards to MS would it be unethical for them to prescribe the drug? My neurologist said that even when the drug is approved, he is still going to keep on prescribing Rituximab anyways. He said the drug salesman can kiss his $ss. He dislikes the price gouging drug companies to say the least. How do others think this will play out in the battle of Rituximab vs. Ocrelizumab?

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    1. Ocrelizuumab use with be a licensed for the MS indication. Rituximab is not, one wonders what Roche will do as the makers of both drugs. We know rituximab makes more neutralising antibodies than ocrelizumab and also if insurance companies will not pay then things may change.

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    2. Dear MouseDoctor,
      As far as I know, there has been now published study comparing the immungenicity of rituximab with ocrelizumab head to head with the same method. If you have any reference for this, could you please post it on the blog?

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    3. There is data from the trial that less than 1% develop neutralizing antibodies with ocrelizumab compared to about 30% for rituximab. This information is from different studies. The non-MSers the rate is lower.

      I suspect that immunogenicity will become a marketing issue.

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  2. Dear PML
    I have removed both your and my comments for the time being and amended the post, I will confer with my Colleges to determine if I am mistaken.

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    1. I seen that the content is online and have re watched the talk and there was insufficient data presented to determine whether CD20 has value as an induction therapy and therapy was apparently typically at 6 month intervals. Comments made about induction during question time was about how treatment was initiated and not induction..We have to get rid of this term.

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  3. My experience is that neuros in US are reluctant to prescribe off-label, & insurance cos. try really, really hard to not cover anything, much less off-label, even if less expensive. I don't forsee off-label drug use becoming popular in USA.

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