Rick
>>I was confused by your response, a couple of months ago, in the VDXX thread. Could you please clarify and/or expand?>>
If you get confused by my answers, it is most probably because I am even more confused. Apart from that, I am the one supposed to put the questions here. And your role is to provide the answers.
My query concerned why there might be a difference between the efficacy, that MLN02 and Antegren appears to have in Crohn's disease. While Antegren seems (so far) to have shown enough positive effects to warrant the running of two fairly big pivotal trials, Millennium's cautious reaction to the wrapping-up of their study with MLN02 seems to indicate, that they don't intend to bring this mAb any further. Or at least not for Crohn's.
I found this difficult to understand, as both mAbs are binding the same integrin (alfa4beta7). I thought that this type of binding should prevent the leukocytes from docking and thus also preventing their participation in the inflammatory process.
Judging from what we have seen so far MLN02 seems to have had some effect, but not strong enough to illicit positive PR from the MLNM/DNA camp. While for Antegren the order is still "Full steam ahead". Of course the Antegren team of ELN/BGEN can at this point not afford to declare Antegren a bust. Especially not Elan.
What could then be the cause for this discrepancy in efficacy? (If there indeed is one) Well, the first answer might be that Antegren is not only binding to alfa4beta7, but also to alfa4beta1. I have however "concluded" that this should not be the reason, because the alfa4beta1-VCAM1 binding does not appear to be critical in the gut. It is for the CNS though, which is why Antegren also carries a lot of hope for the MS indication.
So, that left me with a rather big question-mark, until you suggested, that the apparent difference in efficacy might be due to the fact, that the two mAbs are binding to different epitopes on the integrin, implicating that the one chosen by MLNM/DNA is not completely effective in preventing the binding of the lymphocytes to the endothelium.
So, I am not claiming anything here, just trying to put the few pieces I have managed to come across into a picture, that makes some sense to me.
Erik |
