Tuesday, 22 September 2015

Pharma are like sharks once they smell blood they all join the party

Holgate RG, Weldon R, Jones TD, Baker MP Characterisation of a Novel Anti-CD52 Antibody with Improved Efficacy and Reduced Immunogenicity.PLoS One. 2015 Sep 15;10(9):e0138123.

Anti-CD52 therapy has been shown to be effective in the treatment of a number of B cell malignancies, hematopoietic disorders and autoimmune diseases (including rheumatoid arthritis and multiple sclerosis); however the current standard of treatment, the humanized monoclonal antibody alemtuzumab, is associated with the development of anti-drug antibodies in a high proportion of patients. In order to address this problem, we have identified a novel murine anti-CD52 antibody which has been humanized using a process that avoids the inclusion within the variable domains of non-human germline MHC class II binding peptides and known CD4+ T cell epitopes, thus reducing its potential for immunogenicity in the clinic. The resultant humanized antibody, ANT1034, was shown to have superior binding to CD52 expressing cells than alemtuzumab and was more effective at directing both antibody dependent and complement dependent cell cytotoxicity. Furthermore, when in the presence of a cross-linking antibody, ANT1034 was more effective at directly inducing apoptosis than alemtuzumab. ANT1034 also showed superior activity in a SCID mouse/human CD52 tumour xenograft model where a single 1 mg/Kg dose of ANT1034 led to increased mouse survival compared to a 10 mg/Kg dose of alemtuzumab. Finally, ANT1034 was compared to alemtuzumab in in vitro T cell assays in order to evaluate its potential to stimulate proliferation of T cells in peripheral blood mononuclear cells derived from a panel of human donors: whereas alemtuzumab stimulated proliferation in a high proportion of the donor cohort, ANT1034 did not stimulate proliferation in any of the donors. Therefore we have developed a candidate therapeutic humanized antibody, ANT1034, that may have the potential to be more efficacious and less immunogenic than the current standard anti-CD52.


As soon as you have one successful drug, pharma simply try to copy it as they want a slice of the therapeutic pie. So you have one beta interferon, next you have three. I have lost count of the number of fingolimod mee-toos. Even novartis have made their own me-too called siphonimod. Alemtuzumab is a depleting monoclonal antibody that gets rids of T cells for years, but it is abit rubbish at depleting B cells. However it is licenced and people are smelling the blood.......money. 

So it is not surprising people are making CAMPATH mee-toos. It is amazing that despite depleting white cells out of sight, Alemtuzumab is immunogenic and some people make neutralising antibodies to alemtuzumab. The new me too is more potent than alemtuzumab at killing and may be less immunogenic.  So something to knock AAlemtuzumab off its perch.....Big question is will anti-CD20 have already knocked anti-CD52 of its perch by the time ANT1034 is developed.

CoI: None

14 comments:

  1. At least for fingolimod, it makes sense to develop me-too drugs, in order to eliminate the non-specificity of its S1P binding.

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  2. Talking of sharks, here's an especially egregious example. Not MS related thank goodness but instructive nonetheless.
    http://www.theguardian.com/business/2015/sep/21/entrepreneur-defends-raise-price-daraprim-drug

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    Replies
    1. Remember dimethyl fumarate? Fumaderm=Tecfidera?
      http://www.ncbi.nlm.nih.gov/pubmed/17456929
      http://www.ncbi.nlm.nih.gov/pubmed/10584060

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    2. Seems like the US is finally waking up to the problem. Maybe Martin Shkreli has actually been of some use with his egergious action.
      http://www.theguardian.com/us-news/2015/sep/22/hillary-clinton-promise-treatment-prices-hits-drug-companies-shares-daraprim

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    3. We can only hope that the bad press on this one for the HIV drug is repulsive enough to our legislators that they will take steps to address this problem, but this isn't a new problem and the furor always seems to die down. we'll see if waking up to the problem lasts or if we nod back off.

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  3. Presumably ANT1034 would still have the attendant negative side-effects (development of secondary B cell driven autoimmunity) of alemtuzumab though?

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  4. Why shouldn't they develop me-to therapies? The more MS drugs introduced to the market the higher the prices go also. It's a free for all and this is a result of "the grand bargain". So any 50 year old immunosuppressive drug is an ideal candidate for a new MS therapy, but there is nothing to address the cause or course of the disease.

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    Replies
    1. If the "me toos" actually drove the price of MS drugs down, which would be a huge benefit, there's nothing wrong with that but all evidence so far shows that prices charged are what the market will stand, so they end up costing the same as the existing products. This isn't how markets are supposed to work.

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  5. I think and hope that anti-CD52 treatments are going to look like a version 1.0 product when the 2.0 version comes out. Two weeks today?

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  6. Good, more competition means cheaper prices.
    But this might have an adverse affect also, pharma might opt out investing big money on MS research because any other company can take their product and change a little bit and put it on the market at a much lower cost.

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    Replies
    1. "Good, more competition means cheaper prices."
      Trouble is, all the evidence on pharma pricing shows the complete opposite. Lemtrada being an obvious example.

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    2. One question MD2.
      Do researchers get a slice of the pie on drugs?
      Honest

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    3. Not if they work for pharma, however if they don't work for pharma and invent a drug that gets to market, inventors do get a (very small) slice of the pie after the spoils are shared out with the big guys (the university, funders, pharma partner maybe venture capital etc).

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