Biotech Values

[isolution]

Macugen&Lucentis mechanism

From the Eyetech's propectus (competition), you can read: "The Genentech/ Novartis collaboration is developing an anti-VEGF humanized antibody fragment for intravitreal injection. This product candidate may be viewed as particularly competitive with Macugen because of the similarity of its mechanism of action..
I will not be surprised that Genentech's Lucentis works a little bit better than Macugen. In fact, among the large family of growth factors involved in retinal neovascularisation (VEGF, bFGF, IGF-1, Ang2, PDGF, Interleukin, TNF-alpha), VEGF is thought to be the major mediator. But when you read "anti-VEGF", you ignore a part of the story. The VEGF family includes PIGF, VEGF-A, B, C, D and E. VEGF-A is particulary involved in increased vascular permeability and angiogenesis in the eye. But it has 4 isoforms, VEGF121, 165, 189 and 206. (for more information, read the review from A. Das in progress in retinal and eye research, 22 (2003), p721-748).
The anti-VEGF pegylated aptamer from Eyetech (Eye001, Macugen) binds to the major isoform found in eye disease, VEGF165, although rhuFabV2 monoclonal antibody fragment (Lucentis) binds to all 4 isoforms of VEGF-A.
It is like an antibiotic, it has a broader spectrum.
That is why, I think the molecule from Genentech should be a little bit better than the one from Eyetch, but it will not be spectacular. The only chance is that it shows some improvment when compared to Visudyne, the reference treatment for FDA.
The phase III is also ongoing for Genentech, but I don't think we will see preliminary results before ARVO 2004 in May, except if they try to accelerate the process in view of poor Eyetech's results.
What do you think?