Intravitreal Ziv-Aflibercept: A Comprehensive Review

Barmas-Alamdari, Daniel; D'Souza, Haley; Kapoor, Kapil; Wagner, Alan

doi:10.1080/08820538.2019.1641526

Cited by 13 publications

(10 citation statements)

References 75 publications

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“…Research evaluating the effectiveness of both drugs in the indication of AMD has been conducted for a long time [ 28 , 29 , 30 , 31 ]. In Phase III of the double-blind HAWK clinical trial (NCT02307682), brolucizumab was used in patients with vascular AMD at a dose of 3 mg/50 µL ( n = 358) or 6 mg/50 µL ( n = 360), whereas aflibercept was used at a dose of 2 mg/50 µL ( n = 360).…”

Section: Discussionmentioning

confidence: 99%

The Effectiveness of Brolucizumab and Aflibercept in Patients with Neovascular Age-Related Macular Degeneration

Musiał-Kopiejka¹,

Polanowska²,

Dobrowolski

et al. 2022

IJERPH

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Age-related macular degeneration (AMD) is a progressive, chronic disease of the central area of the retina, which, if untreated, leads to blindness. This study aimed to compare the effectiveness of therapy using anti-VEGF drugs, namely brolucizumab and aflibercept, in patients with neovascular AMD (nAMD) during a monitoring period lasting around 20 weeks. The analysis consisted of 40 patients diagnosed with neovascular age-related macular degeneration, with 20 patients receiving aflibercept (Eylea, Bayer) at a dose of 2 mg/50 µL into the vitreous chamber at the following intervals—3 doses, 4 weeks apart, followed by a fourth dose after 8 weeks. The remaining 20 patients received brolucizumab (Beovu, Novartis) at a dose of 6 mg/50 µL, administered in the following schedule—3 initial doses, 4 weeks apart, with the administration of a fourth dose decided for each patient individually by the doctor, depending on disease activity, assessed through imaging tests. To evaluate treatment effectiveness, the following measurements were used: ‘read distance and near visual acuity’ for each eye separately using the Snellen chart; and non-invasive retinal imaging techniques—optical coherence tomography (OCT) and OCT angiography (OCTA). In patients treated using brolucizumab, during the observation period, statistically significant differences were found in the following parameters: flow area (p = 0.0277); select area (p = 0.0277); FOVEA (p = 0.0073); visus (p = 0.0064). In brolucizumab-treated patients, changes in OCT and OCTA, indicating an improvement, were already visible after the first injection of the drug, whereas in the aflibercept-treated group, changes were only visible after the fourth injection. We found a higher effectiveness of brolucizumab therapy compared to aflibercept in patients with nAMD during an observations period lasting 20 weeks. Our observations are significant, although they require further research.

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Section: Discussionmentioning

confidence: 99%

The Effectiveness of Brolucizumab and Aflibercept in Patients with Neovascular Age-Related Macular Degeneration

Musiał-Kopiejka¹,

Polanowska²,

Dobrowolski

et al. 2022

IJERPH

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“…Ziv-aflibercept (Zaltrap, Sanofi, Paris, France, indicated to treat colon cancer via systemic infusion) contains the same active molecule (aflibercept) but in a different buffer, and is supplied in 4 mL/100 mg and 8 mL/200 mg vials. Ziv-aflibercept can be prepared in a similar manner to bevacizumab for intravitreal injection, and its off-label use to treat nAMD, macular oedema secondary to RVO and DMO, is reviewed elsewhere [ 22 ]. Ziv-aflibercept has been investigated in two Phase I trials with PRN dosing (NCT04290195 and NCT02173873) and is being investigated with up to 12 weekly doing in one Phase 2 trial (NCT02173873), although none of these trials have reported results to date.…”

Section: Amd Dmo Rvo and Uveitismentioning

confidence: 99%

An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma

Ghanchi

Bourne

Downes

et al. 2022

Eye

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In the real-world setting, there is suboptimal compliance with treatments that require frequent administration and assessment visits. This undertreatment frequently has negative consequences in eye disease and carries a real risk to vision. For example, patients with glaucoma risk progression of visual loss even with a small number of missed doses, and patients with neovascular age-related degeneration (nAMD) who fail to attend a bi-monthly clinic appointment to receive an intravitreal anti-vascular endothelial growth factor (VEGF) drug injections may lose the initial vision gains in vision. Protracted regular treatment schedules represent a high burden not only for patients and families, but also healthcare professionals, systems, and ultimately society too. There has been a clear need for longer-acting therapies that reduce the frequency, and therefore the burden, of treatment interventions. Several longer-acting interventions for nAMD, diabetic macular oedema, retinal vein occlusion, uveitis and glaucoma have either been developed or are in late-phase development, some of which employ novel mechanisms of actions, and all of which of promise longer (≥3 month) treatment intervals. This review delivers an overview of anti-VEGF agents with longer durations of action, DARPins, bispecific anti-VEGF/Ang2 therapies, anti-PDGF and anti-integrin therapy, Rho-kinase inhibitors, the Port Delivery System, steroids, gene therapy for retina and uveitis, and for glaucoma, ROCK inhibitors, implants and plugs, and SLT laser and MIGS. The review also refers to the potential of artificial intelligence to tailor treatment efficacy with a resulting reduction in treatment burden.

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“…114 Thus, aflibercept is iso-osmolar, whereas ziv-aflibercept is hyperosmolar relative to the vitreous body. 115 Aflibercept may have an approximately 100-fold greater binding affinity for VEGF-A than either bevacizumab or ranibizumab. Two years into the VISTA and VIVID phase 3 trials, 29.3% to 37.1% of aflibercept-treated eyes experienced DR severity scale improvements of two steps or more compared with 8.2% to 15.6% in sham-treated eyes.…”

Section: Vegf: a Significant Player In The Pathogenesis Of Drmentioning

confidence: 99%

“…Marmor reported that intravitreal ziv‐aflibercept could cause intraocular toxicity, unlike intravitreal aflibercept 114 . Thus, aflibercept is iso‐osmolar, whereas ziv‐aflibercept is hyperosmolar relative to the vitreous body 115 . Aflibercept may have an approximately 100‐fold greater binding affinity for VEGF‐A than either bevacizumab or ranibizumab.…”

Section: Role Of Vegf In Intraocular Neovascular Disordersmentioning

confidence: 99%

Molecular mechanism of VEGF and its role in pathological angiogenesis

Ahmad

Nawaz

2022

J of Cellular Biochemistry

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Over the last seven decades, a significant scientific contribution took place in the delineation of the implications of vascular endothelial-derived growth factor (VEGF) in the processes of angiogenesis. Under pathological conditions, mainly in response to hypoxia or ischemia, elevated VEGF levels promote vascular damage and the growth of abnormal blood vessels. Indeed, the development of VEGF biology has revolutionized our understanding of its role in pathological conditions. Hence, targeting VEGF or VEGFmediated molecular pathways could be an excellent therapeutic strategy for managing cancers and intraocular neovascular disorders. Although anti-VEGF therapies, such as monoclonal antibodies and small-molecule tyrosine kinase inhibitors, have limited clinical efficacy, they can still significantly improve the overall survival rate. This thus demands further investigation through the development of alternative strategies in the management of VEGF-mediated pathological angiogenesis. This review article focuses on the recent developments toward the delineation of the functional biology of VEGF and the role of anti-VEGF strategies in the management of tumor and eye pathologies. Moreover, therapeutic angiogenesis, an exciting frontier for the treatment of ischemic disorders, is highlighted in this review, including wound healing.

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Intravitreal Ziv-Aflibercept: A Comprehensive Review

Cited by 13 publications

References 75 publications

The Effectiveness of Brolucizumab and Aflibercept in Patients with Neovascular Age-Related Macular Degeneration

The Effectiveness of Brolucizumab and Aflibercept in Patients with Neovascular Age-Related Macular Degeneration

An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma

Molecular mechanism of VEGF and its role in pathological angiogenesis

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