Wilder,
I have several time (here at SI) discussed C225, and this is last time that I respond.
First, I will suggest to you or anyone who have interest on this issue to do broad (I mean broad) DD. Target is too important to miss anything, even small peace of puzzle which can bring light forward.
Second, I have investment interest in ABGX, so my view (picture) may be colored.
First about C225,
This is chimerized mAb and IMCL have license drug from ACSD. However, Genentech patent may cover some of the aspect for their antibody.
C225 is NOT potent antibody. Very high doses are in trials 6 mg/kg weekly (compared this with, for instance, Herceptin which is 0.2 mg/kg) and drug did show immunogenecity (HACA) as well as high rate of the diarrhea as side effect.
This antibody never confirmed efficacy as monotherapy, while OSIP and Zeneca small molecule did (and I hope ABX-EGF will beat both small compounds in efficacy).
I will be looking very deep in C225-combination side effects profile and relative to therapy duration, as well long term survival rate (not in response rate, their trial does not have control arm) for refractory colorectal cancer.
They will need ~20% objective response rate in refractory CC to convince FDA that drug is approvable, if one account recent progress in CC with chemo-combination.
While IMCL have Merck KG as EU partner (and loan from Merck for manufacturing facility construction), Merck also had license MEDX EGFr antibody, from 10K-2000;
“We originally developed MDX-447 in conjunction with Merck KGaA. Merck has the rights to commercialize MDX-447 in Europe, to negotiate for co- marketing or co-promotion rights in the United States, and has a 50% commercial interest outside Europe and the United State.... The commercial rights to our MDX-447 and MDX-220 products were transferred to IDM pursuant to this agreement. “
I am sure that Genentech (based on Rituxan and Herceptin success and experience) did took very deep look at C225. However, they went with OSIP. I believe that anti-HER-EGF combo will be tomorrow “real killer”, this receptors heterodimerize. DNA was to slow with ABGX, and IMNX offer 50% share-right, while this is not common for DNA.
ABX-EGF
ABGX completed 7 different doses (weekly) multiple cancer type PI clinical trials. However, they expanded this trial with additional pts in intermediate doses (maybe with different schedule). This can be viewed as problem at higher doses, or better understanding potency of mid doses. I think that it is second and also is oriented toward better understanding of the single agent efficacy/mechanisms. In any event, they can continue to develop ABX-EGF as single agent, do only safety trials with chemo-combo, and submit NDA for single agent. No patent can stop oncologists to explore combination.
In next post is AACR ABGX abstract.
Regards the IMCL broad patent, they did not first invented EGFr antibody, they didn’t invented fully human antibodies, they didn’t first invented antibody-chemo combination any, or for EGFr). They only applied this on C225. In my view, their patent will not hold, but we will know more next week when claims were available. Also, Genentech hold patent on EGFr-antibody-cytotoxic combination.
Bottom line, C225 may produce data to support NDA. However, it also have higher chance that label will be limited factor. Also competitions from small molecules are severe and initial edge to be first on market may quickly evaporate.
Miljenko
PS: Hope you did spare some oxygen. :) |
