OBJECTIVE: To evaluate the efficacy of systemic and intravitreous administration of VEGF Trap (aflibercept) in a nonhuman primate model of choroidal neovascularization (CNV). METHODS: VEGF Trap treatment on laser-induced CNV was evaluated in 48 adult cynomolgus monkeys. In the prevention arms of the study, VEGF Trap was administered by intravenous injection (3 or 10 mg/kg weekly) or intravitreous injection (50, 250, or 500 μg/eye every 2 weeks) beginning before laser injury. In the treatment arm, a single intravitreous injection (500 μg) was given 2 weeks following laser injury. Laser-induced lesions were scored from grade 1 (no hyperfluorescence) to grade 4 (clinically relevant leakage). Representative lesions were evaluated histologically. RESULTS: Grade 4 leakage developed at 32.4% and 45.4% of the laser sites in animals receiving intravitreous or intravenous administration of placebo at 2 weeks following laser injury, respectively. In contrast, the development of grade 4 lesions was completely or nearly completely prevented in all groups receiving intravenous or intravitreous injections of VEGF Trap. A single intravitreous injection of VEGF Trap (500 μg) administered following the development of CNV reduced the frequency of grade 4 lesions from 44.4% to 0% within 14 days of treatment. Intravitreous VEGF Trap was well tolerated with either no or only mild ocular inflammation. Histological evaluation showed decreased scores for morphologic features of tissue proliferation in the VEGF Trap prevention groups. CONCLUSIONS: VEGF Trap prevented the development of clinically relevant CNV leakage when administered at the lowest doses tested. Moreover, a single intravitreous injection induced inhibition of active CNV leakage. CLINICAL RELEVANCE: The animal model used in this study has an established track record as a predictor of pharmacologic efficacy of antineovascular drugs in humans having the neovascular, or wet, form of age-related macular degeneration.
OBJECTIVE: To evaluate the efficacy of systemic and intravitreous administration of VEGF Trap (aflibercept) in a nonhuman primate model of choroidal neovascularization (CNV). METHODS:VEGF Trap treatment on laser-induced CNV was evaluated in 48 adult cynomolgus monkeys. In the prevention arms of the study, VEGF Trap was administered by intravenous injection (3 or 10 mg/kg weekly) or intravitreous injection (50, 250, or 500 μg/eye every 2 weeks) beginning before laser injury. In the treatment arm, a single intravitreous injection (500 μg) was given 2 weeks following laser injury. Laser-induced lesions were scored from grade 1 (no hyperfluorescence) to grade 4 (clinically relevant leakage). Representative lesions were evaluated histologically. RESULTS: Grade 4 leakage developed at 32.4% and 45.4% of the laser sites in animals receiving intravitreous or intravenous administration of placebo at 2 weeks following laser injury, respectively. In contrast, the development of grade 4 lesions was completely or nearly completely prevented in all groups receiving intravenous or intravitreous injections of VEGF Trap. A single intravitreous injection of VEGF Trap (500 μg) administered following the development of CNV reduced the frequency of grade 4 lesions from 44.4% to 0% within 14 days of treatment. Intravitreous VEGF Trap was well tolerated with either no or only mild ocular inflammation. Histological evaluation showed decreased scores for morphologic features of tissue proliferation in the VEGF Trap prevention groups. CONCLUSIONS:VEGF Trap prevented the development of clinically relevant CNV leakage when administered at the lowest doses tested. Moreover, a single intravitreous injection induced inhibition of active CNV leakage. CLINICAL RELEVANCE: The animal model used in this study has an established track record as a predictor of pharmacologic efficacy of antineovascular drugs in humans having the neovascular, or wet, form of age-related macular degeneration.
Authors: Antonia M Joussen; Sebastian Wolf; Peter K Kaiser; David Boyer; Thomas Schmelter; Rupert Sandbrink; Oliver Zeitz; Gesa Deeg; Annett Richter; Torsten Zimmermann; Joachim Hoechel; Ulf Buetehorn; Walter Schmitt; Brigitte Stemper; Michael K Boettger Journal: Br J Clin Pharmacol Date: 2018-11-25 Impact factor: 4.335
Authors: Nori Nagai; Meihua Ju; Kanako Izumi-Nagai; Scott J Robbie; James W Bainbridge; David C Gale; Esaie Pierre; Achim H P Krauss; Peter Adamson; David T Shima; Yin-Shan Ng Journal: Am J Pathol Date: 2015-07-16 Impact factor: 4.307
Authors: Peter Adamson; Thomas Wilde; Eric Dobrzynski; Caroline Sychterz; Rodd Polsky; Edit Kurali; Richard Haworth; Chi-Man Tang; Justyna Korczynska; Fiona Cook; Irene Papanicolaou; Lemy Tsikna; Chris Roberts; Zoe Hughes-Thomas; James Walford; Daniel Gibson; John Warrack; Jos Smal; Ruud Verrijk; Paul E Miller; T Michael Nork; Jeffery Prusakiewicz; Timothy Streit; Steven Sorden; Craig Struble; Brian Christian; Ian R Catchpole Journal: J Control Release Date: 2016-11-01 Impact factor: 9.776