GTC Biotherapeutics (fka GTCB)

[DewDiligence]

Apropos to ADCC: AMGN’s Vectibix Rejected in EU

On Friday, the CHMP (the decision making body for drug approvals in the EU) rejected AMGN’s Vectibix for colorectal cancer. Although the rejection can be explained by deficiencies in AMGN’s phase-3 trial design, the more relevant takeaway message is that Vectibix is not living up the lofty expectations that AMGN had set for it.

Vectibix binds to the EGF receptor on tumor cells, the same mechanism of action as IMCL’s Erbitux. Vectibix and Erbitux are very similar drugs, but Vectibix was supposed to be better than Erbitux for several reasons: i) it is fully human and thus less likely to induce anaphylaxis; ii) it has stronger binding affinity for the EGF receptor; and iii) it has a longer half-life and can thus be dosed less often.

Well, that was the theory. However, the reality is that Vectibix simply doesn’t seem to work as well as Erbitux in any indication where both drugs have been tested.

What possible explanation can there be for a seemingly superior drug to end up being inferior?

A likely answer is ADCC—or rather the lack thereof: Erbitux has ADCC functionality but Vectibix doesn’t because the Abgenix Xenomouse™ that was used to develop the mAb clone for Vectibix had ADCC functionality bred out of it. Abgenix (which has since been acquired by AMGN) presumably thought that removing ADCC functionality was a smart thing to do, but evidently it wasn’t.

What is the relevance of all this for GTC? Please see #msg-17607391, starting about halfway down.