Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study

Published:August 24, 2018DOI:


      Age-related macular degeneration (AMD) can cause irreversible vision loss leading to blindness. We aim to evaluate the efficacy and safety of intravitreal injections of 0.5 mg conbercept, a new anti–vascular endothelial growth factor (anti-VEGF) drug, for treatment of AMD on a schedule more manageable for patients.


      A prospective, double-masked, multicenter, sham-controlled, phase III randomized trial.


      Patients: Patients with choroidal neovascularization (CNV) secondary to AMD were enrolled and randomized to the conbercept group or the sham control group. Intervention: The conbercept group received intravitreal injections of conbercept (0.5 mg) once monthly for the first 3 months, then once quarterly until month 12 (3 + Q3M). The sham group received first 3 monthly sham injections and then 3 monthly injections of conbercept (0.5 mg) followed by quarterly administrations until month 12. Main Outcome Measures: The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 3.


      A total of 114 patients (91.9%) from 9 sites in China completed the 12-month study. At the 3-month primary endpoint, the mean changes in BCVA from baseline were +9.20 letters in the conbercept group and +2.02 letters in the sham group, respectively (P < .001). At 12 months, the mean changes from baseline in BCVA letter score were +9.98 letters in the conbercept group and +8.81 letters in the sham group (P = .64). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival hemorrhage, and increased intraocular pressure.


      A conbercept dosing regimen of 3 initial monthly administrations followed by quarterly treatments is effective for treatment of AMD. In previous reports, other anti-VEGF agents were unable to maintain similar clinical benefits with the same regimen.
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        • Friedman D.S.
        • O'Colmain B.J.
        • Munoz B.
        • et al.
        Prevalence of age-related macular degeneration in the United States.
        Arch Ophthalmol. 2004; 122: 564-572
        • Kawasaki R.
        • Yasuda M.
        • Song S.J.
        • et al.
        The prevalence of age-related macular degeneration in Asians: a systematic review and meta-analysis.
        Ophthalmology. 2010; 117: 921-927
        • Zou H.D.
        • Zhang X.
        • Xu X.
        • Wang F.H.
        • Zhang S.J.
        Zhonghua Yan Ke Za Zhi. 2005; 41: 15-19
        • Spilsbury K.
        • Garrett K.L.
        • Shen W.Y.
        • Constable I.J.
        • Rakoczy P.E.
        Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization.
        Am J Pathol. 2000; 157: 135-144
        • van Lookeren Campagne M.
        • LeCouter J.
        • Yaspan B.L.
        • Ye W.
        Mechanisms of age-related macular degeneration and therapeutic opportunities.
        J Pathol. 2014; 232: 151-164
        • Regillo C.D.
        • Brown D.M.
        • Abraham P.
        • et al.
        Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1.
        Am J Ophthalmol. 2008; 145: 239-248
        • Hernandez-Pastor L.J.
        • Ortega A.
        • Garcia-Layana A.
        • Giraldez J.
        Ranibizumab for neovascular age-related macular degeneration.
        Am J Health Syst Pharm. 2008; 65: 1805-1814
        • Brown D.M.
        • Michels M.
        • Kaiser P.K.
        • Heier J.S.
        • Sy J.P.
        • Ianchulev T.
        Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study.
        Ophthalmology. 2009; 116: 57-65.e55
        • Schmidt-Erfurth U.
        • Eldem B.
        • Guymer R.
        • et al.
        Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study.
        Ophthalmology. 2011; 118: 831-839
        • Martin D.F.
        • Maguire M.G.
        • Ying G.S.
        • Grunwald J.E.
        • Fine S.L.
        • Jaffe G.J.
        Ranibizumab and bevacizumab for neovascular age-related macular degeneration.
        N Engl J Med. 2011; 364: 1897-1908
        • Heier J.S.
        • Brown D.M.
        • Chong V.
        • et al.
        Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration.
        Ophthalmology. 2012; 119: 2537-2548
        • Haller J.A.
        Current anti-vascular endothelial growth factor dosing regimens: benefits and burden.
        Ophthalmology. 2013; 120: S3-S7
        • Zhang M.
        • Zhang J.
        • Yan M.
        • et al.
        A phase 1 study of KH902, a vascular endothelial growth factor receptor decoy, for exudative age-related macular degeneration.
        Ophthalmology. 2011; 118: 672-678
        • Li X.
        • Xu G.
        • Wang Y.
        • et al.
        Safety and efficacy of conbercept in neovascular age-related macular degeneration: results from a 12-month randomized phase 2 study: AURORA study.
        Ophthalmology. 2014; 121: 1740-1747
        • Li H.
        • Lei N.
        • Zhang M.
        • Li Y.
        • Xiao H.
        • Hao X.
        Pharmacokinetics of a long-lasting anti-VEGF fusion protein in rabbit.
        Exp Eye Res. 2012; 97: 154-159
        • Zhang M.
        • Yu D.
        • Yang C.
        • et al.
        The pharmacology study of a new recombinant human VEGF receptor-fc fusion protein on experimental choroidal neovascularization.
        Pharm Res. 2009; 26: 204-210
        • Jager R.D.
        • Aiello L.P.
        • Patel S.C.
        • Cunningham Jr., E.T.
        Risks of intravitreous injection: a comprehensive review.
        Retina. 2004; 24: 676-698
        • Mordenti J.
        • Cuthbertson R.A.
        • Ferrara N.
        • et al.
        Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration.
        Toxicol Pathol. 1999; 27: 536-544
        • Yu D.C.
        • Lee J.S.
        • Yoo J.Y.
        • et al.
        Soluble vascular endothelial growth factor decoy receptor FP3 exerts potent antiangiogenic effects.
        Mol Ther. 2012; 20: 938-947
        • Gonzalez V.H.
        • Campbell J.
        • Holekamp N.M.
        • et al.
        Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data.
        Am J Ophthalmol. 2016; 172: 72-79
        • Jaffe G.J.
        • Ciulla T.A.
        • Ciardella A.P.
        • et al.
        Dual antagonism of PDGF and VEGF in neovascular age-related macular degeneration: a phase IIb, multicenter, randomized controlled trial.
        Ophthalmology. 2017; 124: 224-234
        • Lu X.
        • Sun X.
        Profile of conbercept in the treatment of neovascular age-related macular degeneration.
        Drug Des Devel Ther. 2015; 9: 2311-2320
        • Wolff B.
        • Vasseur V.
        • Cahuzac A.
        • et al.
        Aflibercept treatment in polypoidal choroidal vasculopathy: results of a prospective study in a Caucasian population.
        Ophthalmologica. 2018; : 1-5
        • Hikichi T.
        Six-year outcomes of antivascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy.
        Br J Ophthalmol. 2018; 102: 97-101
        • Qu J.
        • Cheng Y.
        • Li X.
        • Yu L.
        • Ke X.
        Efficacy of intravitreal injection of conbercept in polypoidal choroidal vasculopathy: subgroup analysis of the Aurora Study.
        Retina. 2016; 36: 926-937

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