Tuesday, 19 August 2014

COP-1 v COP-2

After many year as market leader Copaxone (COP-1) is coming to the end of its patent life and the young pretenders (generics/ me toos) are about to muscle into the glaterimer acetate market. Based on comments on the blog some people making comments (Hope they are not Teva reps), seem to love COP-1. Will it be knocked of its perch.


COP-1 is a random mix of four amino acids found in myelin basic protein, and a lot of other proteins, namely glutamic acid, lysine, alanine, and tyrosine. There are a load of generics companies wanting a slice of the pie. And some of them are just as good , or bad, as the Teva product.

However, there is another version in development (COP-2 really called PI-2301, which has been round the companies), which not a generic but a so called next generation drug. 
In EAE this is claimed to be better than COP-1. There are other more versions COP-3 or COP-4. One has a combination of  tyrosine, phenylalanine, alanine, and lysine that binds better to the MHC complex, which is associated with susceptibility and MS. 

They show that COP-2 (it's not really called this:-)) works when you have subcutaneous injections but just like the COP-1, there is limited good animal data published to show that it blocks relapsing disease when administered subcutaneously after the attacks (is this secret data...just as it appears to be with COP-1?), yet it is already in clinical trials and has a name (Plovamer acetate). 


Will it work ?  Will it make it in the day of the pill?

Savinainen A et al. Differentiating Plovamer Acetate and Glatiramer Acetate: Efficacy and Mechanism of Action in a Preclinical Model of Multiple Sclerosis (P1.187)

Amelioration of proteolipid protein 139-151-induced encephalomyelitis in SJL mice by modified amino acid copolymers and their mechanisms. Stern JN, Illés Z, Reddy J, Keskin DB, Sheu E, Fridkis-Hareli M, Nishimura H, Brosnan CF, Santambrogio L, Kuchroo VK, Strominger JL. Proc Natl Acad Sci U S A. 2004; 101(32):11743-8. Epub 2004 Aug 3.

Modified amino acid copolymers suppress myelin basic protein 85-99-induced encephalomyelitis in humanized mice through different effects on T cells. Illés Z, Stern JN, Reddy J, Waldner H, Mycko MP, Brosnan CF, Ellmerich S, Altmann DM, Santambrogio L, Strominger JL, Kuchroo VK. Proc Natl Acad Sci U S A. 2004;101(32):

Amino acid copolymers that alleviate experimental autoimmune encephalomyelitis in vivo interact with heparan sulfates and glycoprotein 96 in APCs. Koenig PA, Spooner E, Kawamoto N, Strominger JL, Ploegh HL. J Immunol. 2013 Jul 1;191(1):208-16. doi: 10.4049/jimmunol.1300345. Epub 2013


CoI: None Really. Research has been funded by MS-The makers of COP-2 (not its name really).

5 comments:

  1. "Meet the new boss, same as the old boss......" There are 20 AAs and 4 make up the copolymer, how many permutations are possible?:-)

    ReplyDelete
  2. "They show that COP-2 (it's not really called this:-)) works when you have subcutaneous injections but just like the COP-1, there is limited good animal data published to show that it blocks relapsing disease when administered subcutaneously after the attacks"

    I realize your whole goal in life is to save the mouse as quickly as possible, but might the effects of Copaxone not be realized immediately?

    "However, since GA is rapidly degraded in the periphery, it is unlikely that its sufficient amounts can reach to the CNS to compete effectively with myelin antigens or initiate specific immune response. Most views thus currently accept that the therapeutic effect of GA is mediated by the GA-induced immune
    cells that penetrate the CNS."

    http://www.ncbi.nlm.nih.gov/pubmed/23051633

    Looking at it from this view, Cop2 may be no better than Cop1

    ReplyDelete
    Replies
    1. Might the effect of copaxone not be realised immediately.... may well be the case, so if you are happy to take for a few months whilst the effect appears that is your risk, but the idea was based on animal work lasting a few weeks. If that all falls apart you are building your concept on dogey ground. Do we care if it works in animals if it works in humans ..no

      The effect of GA is GA-induced immune responses..may be...but Cop2 was aimed at producing better immune reponses. Why does it take months to generate these responses

      Delete
    2. I suspect that only a fraction of the injected compound is not degraded by the time it reaches the lymph-nodes. This is where GA specific T cells originate and migrate to the brain where they accumulate. It is not an instant process:

      http://www.ncbi.nlm.nih.gov/pubmed/14614135

      Delete

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