曹景泰

　　美国regeneron公司 100044

　　Purpose:To present 18-month clinical data and pre-clinical findings on VEGF Trap-Eye，a fusion protein thatpenetrates all retinal layers binding with high affinity toall VEGF-A isoforms and placental growth factor。

　　Method:In this randomized，double masked，multi-center Phase 2 trial，patients with neovascular AMD received VEGF Trap-Eye 0.5 or2.0 mg monthly or 0.5，2.0，or 4.0 mg quarterly for 12 weeks，followed by PRN dosing to 1 year.In the Extension studies all patients received a 2 mg PRN dosing treatment regimen to 18 months.Anatomic efficacy was measured by OCT，and total lesionarea and choroidal neovascularization(CNV)area as determinedby FA.All OCT and FA images were assessed by central readingcenters.In the pre-clinical studies，effects of VEGF Trap-Eye on the CNV lesion components were evaluated in a model of Matrigel-induced CNV in rats。

　　Results:One year results for all groups combined(n=157)demonstratedsignificant decreases from baseline in central retinal/lesion thickness(CR/LT)of-130μm(p<0.0001).Allgroups combined at 1 year showed significantreductions of active CNV size(mean change of-2.21 mm，p<0.0001)and classic CNV size(mean change of-1.21 mm，p<0.0001).Patients dosed with 2 mg monthly for 12 weeks followedby PRN dosing，in general，achieved the largest improvementsin anatomic as well as visual acuity，up to+9.0 mean letters gained at 1 year.Patients treated with 2 mg PRN dosing maintained their visual improvement to 18 months.In the pre-clinical studies，both CNV vessel and the total lesion volumes were significantly reduced by VEGF Trap treatment(p<0.001).Inflammatory cell infiltration and fibrovascular elements were also deceased by VEGF Trap treatment on established CNV in rats。

　　Conclusions:VEGF Trap-Eye produced significant reductions in CR/LT thickness as well as significant reductions in active CNV andclassic CNV size at 1 year compared to baseline.The visual improvement was durably maintained with less injection frequencies in the extension studies.VEGF Trap-Eye not only promoted regression of CNV，but also diminished the inflammation and fibrosis in the CNV lesion.