<p>Comparing The Efficacy Of An Anti-Human VEGF-A Neutralizing Antibody Versus Bevacizumab On A Laser-Induced Choroidal Neovascularization (CNV) Rhesus Monkey Model</p>

Abstract

PurposeTo 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.MethodsTo 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).ResultsIn 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% (p<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% (p<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% (p<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% (p<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.ConclusionAfter 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.

Pharmacokinetics and Safety of an Intravitreal Humanized Anti-VEGF-A Monoclonal Antibody (PRO-169), a Biosimilar Candidate to Bevacizumab

“… 5 PRO-169 is a biosimilar candidate to BEV, it is structurally similar and has target specificity like BEV does, but it was developed for intravitreal use. 6 , 7 PRO-169 has been determined to be consistent with historical data such as quality, charge of heterogeneity, purity, structure, and binding affinity of commercially available BEV. 6 …”

“…In summary, similar inhibitory effects on angiogenesis between PRO-169 and BEV have been demonstrated in an in vivo preclinical study; PRO-169 has proven to have the same effectiveness in reducing the retinal thickness and fluorescein leakage area in a CNV rhesus monkey model. 7 Also, PRO-169 has demonstrated to be nontoxic to the retina at the 1.25 mg dose tested in NZW rabbit eyes. 6 Here, we report the results of the intraocular pharmacokinetics profile after a single intravitreal injection of PRO-169 and, in order to ensure that PRO-169 is safe after repeated injections, three consecutive intravitreal injections were administered at 30-days intervals in a second experiment.…”

Safety and tolerability evaluation after repeated intravitreal injections of a humanized anti-VEGF-A monoclonal antibody (PRO-169) versus ranibizumab in New Zealand white rabbits

“…PRO-169, is a mAb structurally like bevacizumab on target specificity, identity and pharmacokinetics, specific for ophthalmic use. On a laser-induced CNV rhesus monkey model, it demonstrated to be able to reduce the retinal thickness and fluorescein leakage area after treatment for 2 and 4 weeks, without toxic effect or adverse events [4]. However, controlled research in an animal model using electrophysiological and clinical tests after repeated intravitreal injections was needed.…”

“…Many of these have shown that the repeated intravitreal injections of bevacizumab or ranibizumab have no long-term deleterious effects on the electrophysiological and morphologic integrity of the retina [1,[11][12][13][14][15][16][17]. Another preclinical in vivo study reported that after Choroidal Neovascularization (CNV) induction through retinal photocoagulation, PRO-169 administration (1.25 mg per eye) can inhibit the retinal thickness and fluorescein leakage area without toxic effect or adverse events in a rhesus monkey model [4]. Assessing retinal toxicity of PRO-169, through controlled research in an animal model using ERG and clinical tests after repeated intravitreal (Ivt) injections was needed.…”

“…Its presence is necessary in order to maintain the normal functions of the eye, yet it can be harmful when it is overproduced, as it happens in diseases whose pathophysiology is based on neovascularization of the retina. Diabetic retinopathy (DR), age-related macular degeneration (ARMD), retinopathy of prematurity (ROP) and central retinal vein occlusion (CRVO) are some of such diseases; and their prevalence is a real public health threat [ 2 – 4 ]. DR alone affects up to 80% of patients with chronic Diabetes Mellitus, while diabetic macular edema is diagnosed in 16% of them [ 5 , 6 ].…”