Efficacy of simultaneous
            <scp>VEGF</scp>
            ‐A/
            <scp>ANG</scp>
            ‐2 neutralization in suppressing spontaneous choroidal neovascularization

Foxton, Richard; Uhles, Sabine; Grüner, Sabine; Revelant, Franco; Ullmer, Christoph

doi:10.15252/emmm.201810204

Cited by 48 publications

(48 citation statements)

References 8 publications

(11 reference statements)

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“…Initial studies showed that vitreous levels of Ang-2 are elevated in nAMD, diabetic retinopathy (i.e., DME), and retinal vein occlusion [ 19 , 61 , 62 ]. In animal studies, spontaneous choroidal neovascularization models show faricimab and other VEGF-A/Tie-2 targeting agents reduce vessel lesions and neuron loss, inhibit retinal leukocyte infiltration, and prolong the anti-leakage effect [ 62 , 63 ]. Preclinical studies showed that blocking Ang-2 reduces VEGF-induced endothelial barrier breakdown [ 62 , 64 ].…”

Section: Clinical Studies Of Faricimab In Diabetic Macular Edemamentioning

confidence: 99%

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Khan

Aziz

Shafi

et al. 2020

Cells

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This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.

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Section: Clinical Studies Of Faricimab In Diabetic Macular Edemamentioning

confidence: 99%

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Khan

Aziz

Shafi

et al. 2020

Cells

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“…In July 2017, the journal issued an editorial expression of concern (https://doi.org/10.15252/emmm.201707895) to alert readers that the data in Figs 4 and 5 needed further analysis and verification. Researchers at Roche have since confirmed in an independent study based on independently obtained data that the conclusions from these figures are valid (Foxton et al , ).…”

mentioning

confidence: 88%

Targeting key angiogenic pathways with a bispecific Cross MA b optimized for neovascular eye diseases

Regula¹,

Leithner²,

Foxton³

et al. 2019

EMBO Mol Med

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“…Due to its additional role in inflammation that is implicated in wet AMD, ANG2 has become a potential therapeutic target in wet AMD beyond anti-VEGF therapies (Gahn and Khanani, 2018). In vivo experiments have recently demonstrated ANG2 and VEGF combinatory inhibition led to reduced neovascular lesion formation in a spontaneous chronic choroidal neovascularization mouse model (JR5558 mice) (Foxton et al, 2019). This has been carried forward to phase 1 and 2 clinical trials with the bispecific antibody anti-VEGF-A/ANG2 (RG7116; Roche/Genetech).…”

Section: Vascular Mechanisms In Choroidal Neovascularizationmentioning

confidence: 99%

Choroidal Neovascularization: Mechanisms of Endothelial Dysfunction

2019

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Many conditions affecting the heart, brain, and even the eyes have their origins in blood vessel pathology, underscoring the role of vascular regulation. In age-related macular degeneration (AMD), there is excessive growth of abnormal blood vessels in the eye (choroidal neovascularization), eventually leading to vision loss due to detachment of retinal pigmented epithelium. As the advanced stage of this disease involves loss of retinal pigmented epithelium, much less attention has been given to early vascular events such as endothelial dysfunction. Although current gold standard therapy using inhibitors of vascular endothelial growth factor (VEGF) have achieved initial successes, some drawbacks include the lack of long-term restoration of visual acuity, as well as a subset of the patients being refractory to existing treatment, alluding us and others to hypothesize upon VEGF-independent mechanisms. Against this backdrop, we present here a nonexhaustive review on the vascular underpinnings of AMD, implications with genetic and systemic factors, experimental models for studying choroidal neovascularization, and interestingly, on both endothelial-centric pathways and noncell autonomous mechanisms. We hope to shed light on future research directions in improving vascular function in ocular disorders.

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Efficacy of simultaneous VEGF ‐A/ ANG ‐2 neutralization in suppressing spontaneous choroidal neovascularization

Cited by 48 publications

References 8 publications

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Targeting key angiogenic pathways with a bispecific Cross MA b optimized for neovascular eye diseases

Choroidal Neovascularization: Mechanisms of Endothelial Dysfunction

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