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Peter Lundh von Leithner, Daiju Iwata, Y. Ng, Jorg Regula, Guido Hartmann, David T Shima; Bispecific anti-VEGF/ANG2 antibody exhibits superior efficacy to VEGF monotherapy in a model of spontaneous CNV. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2356.
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Anti-vascular endothelial growth factor-A (anti-VEGF) therapy has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Next generation treatment goals include achieving a reduced treatment frequency and improving upon the efficacy of existing treatment options. In terms of efficacy, data from pivotal trials of anti-VEGF drugs show that despite the improvement in central vision for many patients, the majority still see 20/50 or worse. To explore improving upon existing treatments, we investigated a combination therapy strategy targeting VEGF-A and angiopoietin 2 (Ang2)
A mouse model (JR5558) that develops multi-focal, bi-lateral spontaneous choroidal neovascularization (CNV) was used to assess effects of anti-VEGF, anti-ANG2 or a bispecific antibody combination of the two antagonists. Drugs were administered for a two week period, either during the initiation of angiogenesis (prevention mode), or after CNV vessels were established (intervention mode). Drug efficacy was assessed in vivo using fluorescein (FA) and indocyanine green angiography (ICGA), optical coherence tomography and ERG. Various ex-vivo assessments (isolectin-B4, endomucin, F4/80, GFAP and TUNEL) were used to assess neovessel, macrophage, glial and photoreceptor outcomes.
Bispecific anti-VEGF/ANG2 treatment consistently outperformed monospecific antibodies alone in both prevention and intervention experiments. Reduction in vascular growth, leakage, edema, and photoreceptor loss was superior in the bi-specific antibody treatment groups. Full field ERG data also suggest the bi-specific may provide better visual function outcomes.
Targeting Ang2 in addition to VEGF-A may provide a new strategy for the improved management of nAMD
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