DA VINCI: DME And VEGF Trap-Eye: INvestigation of Clinical Impact: Phase 2
`study in patients with Diabetic Macular Edema (DME)
`
`Author: David Brown, MD
`
`BACKGROUND
`VEGF Trap is a recombinant fusion protein consisting of VEGF binding domains of
`human VEGF receptors 1 and 2 fused to the Fc domain of human IgG1. VEGF Trap-Eye
`has demonstrated bioactivity and safety in a phase 1 study of diabetic macular edema.
`
`PURPOSE
`Present detailed efficacy and safety analyses of the primary 24-week endpoint from the
`Phase 2 study assessing VEGF Trap-Eye vs. laser photocoagulation in DME.
`
`METHODS
`DA VINCI is a multi-center, randomized, active-controlled Phase 2 clinical study,
`designed to assess safety and efficacy of 4 dose/dose intervals of VEGF Trap-Eye (VTE)
`in comparison to laser photocoagulation. 221 patients were randomized (219 treated) to 1
`of the following treatment groups: 0.5mg q4wks, 2mg q4wks, 2mg q8wks, 2mg prn or
`laser photocoagulation. The primary endpoint is the mean change from baseline in BCVA
`at week 24. Secondary endpoints include changes in retinal thickness (CRT) on OCT and
`central retinal sensitivity. Central retinal sensitivity was measured using the Nidek MP-1
`microperimeter with values corresponding to the OCT central subfield.
`
`RESULTS
`At 6 months, the mean change in BCVA for each VTE group ranged from +8.5 to +11.4
`letters and was statistically significantly better than the mean change in BCVA in the
`laser group (+2.5 letters; p<0.001), and no significant difference was noted among the
`VTE arms. Anatomical changes were significant as well. Mean change in CRT for each
`VTE group ranged from -127μm to -195μm and was statistically significantly greater
`than the mean change in CRT for the laser group (-68μm; p<0.01). VTE arms had a
`mean gain in central retinal sensitivity ranging from 1.5 to 4.1dB, while the laser arm had
`a mean decrease of -0.4dB. VEGF Trap-Eye was generally well-tolerated, and adverse
`events reported were those typically associated with intravitreal injections or underlying
`disease. The most frequent adverse events reported in the VTE arm included conjunctival
`hemorrhage, eye pain, floaters, ocular hyperemia, and increased IOP.
`
`CONCLUSION
`In this patient population, VTE was generally well tolerated and produced statistically
`significant improvements from baseline in visual acuity, retinal thickness and central
`retinal sensitivity as compared to laser photocoagulation.
`
`Regeneron Pharmaceuticals, Inc. Exhibit 2022 Page 1
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
`
`