Dew slides and comments
Slide 5: Any idea what “Supplemental Oxygen” refers to?
I suppose it's related to lack of Oxygen for preterm babies at birth being the main cause of a disease called ROP (retinopathy of prematurity) which is the main cause of the lost of vision for small babies (very rare, hoppefully)
Slide 15: This slide is missing from your post.
it is an image dealing with the ligand mechanism in neovascularization and what happen when they don't polymerize.
Slide 17: Unlike GENR’s Squalamine trial, CA4P patients were allowed to have received prior Visudyne. I wonder how this will complicate analysis of the effect of CA4P.
As Combretastatin act on already formed and remaining neovessel, I think it doesn't matter, to show better efficacy I would have chosen like GENR, but that their choice. I will investigate.
Slide 18: “FA and OCT immediately after first infusion, and just prior to next 3 infusions”. I do not know what FA and OCT mean.
Fundus angiography (picture of vessels at the back of the eye, some kind of mapping) and OCT is thickness measurement of the retina tissue (I don't remenber the exact wording)
Slide 19: It says four patients have completed treatment, but I do not see a reference to “18 eyes” having been treated as was mentioned on the OXGN message board. Is that information in there somewhere?
Me either, I don't find this number.
Slides 20-31: If it’s not too much trouble, I would be interested in these results.
Slide 20:Intravitreous rhuFab V2 Multicenter Phase III Clinical Trial
Monoclonal antibody fragment directed against VEGF
Designed for complete inhibition of all VEGF isoforms.
Reduces vascular permeability
Inhibits angiogenesis
Access to all sites of VEGF production
Slide 21 What Is VEGF?
“Vascular Endothelial Growth Factor”
Homodimeric glycoprotein (165 AA)
Secreted by a variety of cells in response to hypoxia/ischemia and other signaling molecules
Induces vascular permeability and angiogenesis
5 isoforms produced in human, VEGF165 most abundant
Slide 22 What Does VEGF Do?
Normal Development: essential for normal embryonic development
Corrective: wound, bone repair
Malignancy: over-expressed in many tumors
Non-malignant conditions: pathologic neovascularity of the sub-retinal choroidal vessels
Slide 23 What Is rhuFabV2 ?
recombinantly produced
humanized
Fab fragment
Mouse Monoclonal Ab against VEGF
V2 – Version 2 Affinity Matured
Generic name: “Ranibizumab”
Slide 24 rhuFabV2 – How It Works
No rhuFab V2
High [VEGF]
VEGF Stimulates
-cell proliferation
-cell migration
-vascular permeability
Presence of rhuFab V2
Low active [VEGF]
No Stimulation of
-cell proliferation
-decreased permeability
Slide 25 rhuFabV2 – What It Does
VEGF binds receptors
Vascular LEAKAGE and swelling
ANGIOGENESIS
rhuFab V2 blocks VEGF
Decreases LEAKAGE and swelling
Blocks ANGIOGENESIS
Slide 26 Intravitreous rhuFab V2 Multicenter Phase III Clinical Trial
PI: Julia Haller, MD
Eligibility
50 years or older
Minimally classic or occult subfoveal CNV due to AMD (MARINA)
CNV 12 MPS DA
VA 20/40 – 20/320
No previous PDT or laser in designated study eye
Slide 27 Intravitreous rhuFab V2 Multicenter Phase III Clinical Trial
Design
Monthly intravitreal injections for 24 months
FA at various visits throughout the study
Outcome variables
Visual acuity
Size of CNV
Slide 28 Intravenous VEGF Trap Phase I/II Clinical Trial
What is VEGF Trap ?
Specific antagonist that binds and inactivates circulating VEGF
Recombinantly produced fusion protein consisting of 2 different human VEGF receptor extracellular domains fused to the Fc portion of human IgG1
Slide 29 Intravenous VEGF Trap Phase I/II Clinical Trial
What is VEGF Trap ?
Contains sequences encoding Ig domain 2 from VEGFR1 fused to Ig domain 3 from VEGFR2, which then fused to the hinge region of human IgG1 Fc domain
Advantages over other VEGF blockers
Higher affinity for VEGF than a humanized monoclonal antibody
Longer circulating half-life
Slide 30 Intravenous VEGF Trap Phase I/II Clinical Trial
PI: Quan Dong Nguyen, MD
Eligibility
Age: > 50 yo
Visual acuity: 20/40- 20/800
Predominantly classic, minimally classic, or occult subfoveal CNV due to AMD
CNV 12 MPS DA
Blood and fibrosis 50% of lesion
If eligible for PDT, can enter trial if refuses PDT
Patients allowed to have previous PDT
Slide 31 Intravenous VEGF Trap Phase I/II Clinical Trial
Design
60-minute IV infusions x 4
Dose escalation: 3 dose levels for 3 cohorts of patients (8 patients per cohorts)
Randomization: 3:1 (drug : placebo)
FA and OCT at various study visits
Follow for 6 weeks after last infusion
Outcome variables
Visual acuity
Retinal thickness and subretinal fluid by OCT
Size of CNV
Enrollment
To be opened in December 2003
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