Olvera-Montaño Oscar, Baiza-Duran Leopoldo, Quintana-Hau Juan D, Quiñonez-Alvarado Mayra G, Zeng Wen, Gong Li, Muñoz-Villegas Patricia
Clinical Research Department, Laboratorios Sophia, SA De CV, Zapopan, Jalisco, Mexico.
Research and Development Department (CIS), Zapopan, Jalisco, Mexico.
Drug Des Devel Ther. 2019 Nov 4;13:3813-3821. doi: 10.2147/DDDT.S219350. eCollection 2019.
To evaluate the efficacy of a therapy on improving characteristics of laser-induced choroidal neovascularization (CNV) via single intravitreal injection of a humanized anti-human VEGF monoclonal antibody (PRO-169) versus bevacizumab in a rhesus monkey model.
To induce experimental CNV, small high-energy laser spots were used to treat several areas, around the macula in the retinas of monkeys at Day -21. Eighteen rhesus monkeys were used for CNV induction. The efficacy endpoints were fluorescein leakage by FFA and retinal thickness by OCT. FFA examinations were performed 19 days after induction. Appropriate animals were enrolled for treatment and randomly divided into 3 groups: bevacizumab (n=5, 7 eyes), PRO-169 (n=5, 7 eyes), and vehicle controls (n=4, 7 eyes).
In 25 of 36 (69.4%) eyes, CNV lesions were identified. The average percent change of retinal thickness in the eyes of bevacizumab group was -159.3±62.2% and -154.0±45.1% (<0.01 vs Vehicle) at Day 14 and Day 28, respectively; in the eyes of PRO-169 group it was -131.6±68.7% and -131.5±63.8% (<0.01 vs Vehicle), respectively. The average percent change of leakage area in the eyes of bevacizumab group was -75.3±49.4% and -78.0±42.6% (<0.01 vs Vehicle) at Day 14 and Day 28, respectively; in the eyes of PRO-169 group it was -82.0±19.3% and -81.4±21.0% (<0.01 vs Vehicle), respectively. There were no abnormalities found in behavior, skin and hair, excretion and overall eye appearance before and after treatment in all groups.
After photocoagulation, the eyes enrolled in this studio showed CNV related characteristics including increased retinal thickness, and fluorescein leakage at laser spots. PRO-169 (1.25 mg per eye) can reduce the retinal thickness and fluorescein leakage area after treatment for 14 and 28 days in this rhesus monkeys model, without toxic effect or adverse events. These findings suggested that PRO-169 can inhibit CNV.
在恒河猴模型中,通过玻璃体内单次注射人源化抗人VEGF单克隆抗体(PRO - 169)与贝伐单抗,评估一种疗法改善激光诱导脉络膜新生血管(CNV)特征的疗效。
为诱导实验性CNV,在第 - 21天使用小的高能激光光斑治疗恒河猴视网膜黄斑周围的多个区域。18只恒河猴用于诱导CNV。疗效终点为荧光素血管造影(FFA)显示的荧光素渗漏和光学相干断层扫描(OCT)显示的视网膜厚度。诱导后19天进行FFA检查。将合适的动物纳入治疗并随机分为3组:贝伐单抗组(n = 5,7只眼)、PRO - 169组(n = 5,7只眼)和载体对照组(n = 4,7只眼)。
36只眼中的25只(69.4%)发现有CNV病变。贝伐单抗组在第14天和第28天视网膜厚度的平均变化百分比分别为 - 159.3±62.2%和 - 154.0±45.1%(与载体对照组相比<0.01);PRO - 169组分别为 - 131.6±68.7%和 - 131.5±63.8%(与载体对照组相比<0.01)。贝伐单抗组在第14天和第28天渗漏面积的平均变化百分比分别为 - 75.3±49.4%和 - 78.0±42.6%(与载体对照组相比<0.01);PRO - 169组分别为 - 82.0±19.3%和 - 81.4±21.0%(与载体对照组相比<0.01)。所有组在治疗前后的行为、皮肤和毛发、排泄及整体眼部外观均未发现异常。
光凝后,本研究中的眼睛出现了与CNV相关的特征,包括视网膜厚度增加和激光光斑处的荧光素渗漏。在该恒河猴模型中,PRO - 169(每只眼1.25 mg)在治疗14天和28天后可减少视网膜厚度和荧光素渗漏面积,且无毒性作用或不良事件。这些发现表明PRO - 169可抑制CNV。