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

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