Abstract
Wet age‐related macular degeneration (wet‐AMD) is a leading cause of irreversible blindness. Current treatment of AMD requires monthly intravitreal injection, which is difficult to be implemented in many parts of the world. In recent years, controlled release of anti‐vascular endothelial growth factor (VEGF) therapeutics has attracted intense research interest aiming to reduce the injection frequency to one or two times per year. In this study, we evaluated the in vivo pharmacokinetics and the long‐term therapeutic efficacy of an in situ hydrogel encapsulating an anti‐VEGF antibody in nonhuman primates. We show that after a single injection of anti‐VEGF controlled release hydrogel, a relatively constant concentration of drug can be maintained in the monkey eye for at least 5 months and the dose was sufficient for the treatment of recurrent choroidal neovascularization induced by repeat laser photocoagulation in monkeys. Our result suggested that when formulated into a controlled release formulation, a single dose of anti‐VEGF may be sufficient for a half‐year treatment and controlled release may be a suitable strategy to reduce the injection frequency in the treatment of AMD in human.
Highlights
Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has been the first line treatment for wetAMD since the introduction of anti-VEGF antibody/antibody fragment in 2005.4,5 Compared to pre-anti-VEGF treatment options, including vitamin supplies and photodynamic therapy, where the patient's visual acuity (VA) would continue to decline after treatment,[6,7] intravitreal injection of anti-VEGF is able to improve patients' VA
The invention of anti-VEGF therapy and the success of clinical use were encouraging; the once-per-month injection scheme for the management of chronic eye diseases was impossible to be implemented in most parts of the world
There has been a growing interest to reduce the number of anti-VEGF injection
Summary
Wet age-related macular degeneration (wet-AMD) is one of the leading causes of irreversible blindness.[1,2,3] Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has been the first line treatment for wetAMD since the introduction of anti-VEGF antibody/antibody fragment (bevacizumab or Avastin [off label use for ophthalmic indications], and ranibizumab or Lucentis) in 2005.4,5 Compared to pre-anti-VEGF treatment options, including vitamin supplies and photodynamic therapy, where the patient's visual acuity (VA) would continue to decline after treatment,[6,7] intravitreal injection of anti-VEGF is able to improve patients' VA. It is practically impossible, in terms of the requirement of financial and healthcare resources, for most patients to maintain such injection frequency.[14] anti-VEGF is effective in treating diabetic macular edema and proliferative diabetic retinopathy, but the requirement of repeated injection forced most patients to choose the less effective laser treatment.[15]. In terms of the requirement of financial and healthcare resources, for most patients to maintain such injection frequency.[14] anti-VEGF is effective in treating diabetic macular edema and proliferative diabetic retinopathy, but the requirement of repeated injection forced most patients to choose the less effective laser treatment.[15] To overcome these obstacles, intravitreal controlled release systems that aim to prolong the therapeutic duration of anti-VEGF has been actively pursued over the past 10 years in both industry and academia. Using the Blob model as a guidance for rational design, we were able to identify formulations that released bevacizumab in vivo in rabbit eyes for over 6 months with excellent biocompatibility.[21,22] In this study, we aim to confirm the ocular biocompatibility in nonhuman primates, and evaluate the in vivo pharmacokinetics and long-term therapeutic effect of the controlled release formulation in a nonhuman primate model with recurrent choroidal neovascularization (CNV)
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