New Treatment Modalities for Neovascular Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is considered one of the main causes of severe vision loss in older adults. The neovascular form (nAMD) is an advanced stage, which is responsible for the most severe vision loss. Vascular endothelial growth factor (VEGF) is at present the main factor that leads to the development of a neovascular membrane and the increased leakage from the membrane to the retina. At present, anti-VEGF therapy is the only treatment that achieves vision gains in many patients and halts progression in most of them. VEGF blockade can be achieved with several molecules and various treatment regimens, which have been studied with excellent results. Unfortunately, real-world data has shown to be far less efficacious than clinical trials. This gap between clinical trials and real-world results is an unmet medical need that supports the necessity of new treatment modalities for nAMD. Of the various treatments being studied, anti-VEGFs of higher efficacy and longer durability are those more advanced in their development. Brolucizumab and abicipar pegol are 2 new anti-VEGF drugs that had positive results in phase 2 studies and are being tested in phase 3 trials at present. Other promising therapies are antiangiopoietin 2 molecules, which are in phase 2 development. At earlier stages of development but with promising results are squalamine, anti-VEGF-C and -D, and gene therapy. The future will give retina specialists a broad armamentarium with which patients may achieve high visual gains for the long term with a low treatment burden.

Treat-and-extend therapy using intravitreal aflibercept for neovascular age-related macular degeneration: 2-year real-world practice data from Slovenia

“…Age-related macular degeneration (AMD) is one of the leading causes of visual impairment in industrialised countries [1]. The advanced stage of the disease, neovascular AMD (nAMD), is responsible for the most severe vision loss and can have a debilitating effect on quality of life [2, 3]. The unravelling of the core molecular mechanisms of nAMD has led to the approval of two robust anti-vascular endothelial growth factor (VEGF) therapies which have now become the standard of care [4, 5].…”

Ranibizumab port delivery system: a clinical perspective

“…However, despite these promising results, other studies have observed inferior VA results in real-world T&E treatment regimens in comparison with the controlled treatment provided in clinical trials. 17 24 25 One study found that only 13% of patients under T&E regimens were truly able to reach and maintain a 12-week treatment interval, only 10% able to maintain an 8-week interval, and 27% were not able to maintain even an 8-week interval. 26 This disparity between real-world and clinical trial VA outcomes of T&E regimens is thought to be due to the still-relatively-high treatment burden of frequent office visits, which itself represents the summative difficulties of patient and provider time/scheduling constraints, the need for caregivers to accompany patients, socioeconomic factors, and dissatisfaction with initial visual acuity results.…”

“… 24 25 28 Given mixed results from real-world studies that use the T&E regimen, in addition to its risk of undertreating patients highlighted in some studies, a need remains for alternative, longer-lasting treatments that are comparable in efficacy to the original standard set by monthly ranibizumab in its pivotal clinical trials while foregoing its burdensome administration schedule. 17 24 25 …”

“…Although frequent ranibizumab injections have proven effective in halting the progression of vision loss in many patients with nAMD, the monthly injection schedule studied with the initial registration trials exemplifies a significant treatment burden for patients in addition to the increased cost and risk inherent to repeated intravitreal injections 15. In addition, observational studies in real-world clinical practice have shown that patients are unable to achieve similar benefits as those seen in clinical trials due to the high associated treatment burden 2 16 17. Since then, studies were initiated to determine treatment regimens that would form a compromise between patient burden and adequate treatment coverage.…”

<p>Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date</p>

“…One promising solution to greatly reduce injection frequency and maintain pharmacological efficacy is an implantable device that can deliver the controlled release of VEGF neutralizing agents. 18 The most promising implant that is undergoing late phase clinical trials is the ranibizumab port delivery system (PDS), a small, refillable eye implant that dispenses ranibizumab. This review covers the current evidence to date of the therapeutic potential of the ranibizumab port delivery system in the treatment of nAMD.…”