Emerging therapies and their delivery for treating age-related macular degeneration.

Chloe N Thomas,Alastair K Denniston,Wen Hwa Lee,Lisa J Hill,Nada Alfahad,Andrew D Dick,Dawn A Sim

doi:10.1111/bph.15459

Abstract

Age-related macular degeneration (AMD) is the most common cause of blindness in the Western world and is characterised in its latter stages by retinal cell death and neovascularisation and earlier stages with the loss of parainflammatory homeostasis. Patients with neovascular AMD (nAMD) are treated with frequent intraocular injections of anti-vascular endothelial growth factor (VEGF) therapies, which are not only unpopular with patients but carry risks of sight-threatening complications. A minority of patients are unresponsive with no alternative treatment available, and some patients who respond initially eventually develop a tolerance to treatment. New therapeutics with improved delivery methods and sustainability of clinical effects are required, in particular for non-neovascular AMD (90% of cases and no current approved treatments). There are age-related and disease-related changes that occur which can affect ocular drug delivery. Here, we review the latest emerging therapies for AMD, their delivery routes and implications for translating to clinical practice. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.

Highlights

Age-related macular degeneration (AMD) is the most common cause of visual loss in the developed world with $196 million people worldwide living with AMD, which is predicted to rise to 288 million by 2040 (Wong et al, 2014)
In the STAIRWAY Phase II trial (NCT03038880), 6 mg of faricimab was intravitreally injected every 12 or 16 weeks which resulted in the maintenance of initial vision and anatomical improvements, comparable with monthly ranibizumab injections at 52 weeks (Khanani, Patel, et al, 2020). These results suggest a role for simultaneous neutralisation of Ang2 and vascular endothelial growth factor (VEGF)-A in providing sustained efficacy through extended durability
There are many emerging therapeutic agents in pre-clinical development and clinical trials for AMD. These could provide a complementary therapy in combination with existing anti-VEGF therapies for neovascular AMD (nAMD) patients and provide a less invasive delivery route or longer acting effect and reduce the number of intravitreal injections required

Summary

Introduction

Age-related macular degeneration (AMD) is the most common cause of visual loss in the developed world with $196 million people worldwide living with AMD, which is predicted to rise to 288 million by 2040 (Wong et al, 2014). NAMD patients are treated with long-term, regular intravitreal injections of anti-vascular endothelial growth factor (VEGF) therapies (e.g., bevacizumab and aflibercept), aimed to reduce angiogenesis, oedema and stabilise vision loss.

Results

Conclusion