Safety and Efficacy of Different Doses and Regimens of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration

Sahni, Jayashree; Dugel, Pravin U.; Patel, Sunil; Chittum, Mark E.; Berger, Brian B.; Rubido, Marta del Valle; Sadikhov, Shamil; Szczęsny, Piotr; Schwab, Dietmar; Nogoceke, Everson; Weikert, Robert J.; Fauser, Sascha

doi:10.1001/jamaophthalmol.2020.2685

Cited by 98 publications

(85 citation statements)

References 37 publications

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“…For retinal and choroidal diseases, three molecules targeting the Ang/Tie pathway have been studied in phase 2 trials for DMO and nAMD. These include the VE-PTP inhibitor AKB-9778 (Aerpio Pharmaceuticals, Inc.) [ 91 ], anti–Ang-2 antibody nesvacumab and aflibercept combination therapy (Regeneron Pharmaceuticals, Inc.) [ 92 ] and the bispecific anti–Ang-2/anti–VEGF antibody faricimab (F. Hoffmann-La Roche Ltd.) [ 93 , 94 ]. Efficacy of AKB-9778 was assessed in patients with DMO and non-proliferative DR.…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Joussen

Ricci

Paris

et al. 2021

Eye

113

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The angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) pathway is an emerging key regulator in vascular development and maintenance. Its relevance to clinicians and basic scientists as a potential therapeutic target in retinal and choroidal vascular diseases is highlighted by recent preclinical and clinical evidence. The Ang/Tie pathway plays an important role in the regulation of vascular stability, in angiogenesis under physiological and pathological conditions, as well as in inflammation. Under physiological conditions, angiopoietin-1 (Ang-1) binds to and phosphorylates the Tie2 receptor, leading to downstream signalling that promotes cell survival and vascular stability. Angiopoietin-2 (Ang-2) is upregulated under pathological conditions and acts as a context-dependent agonist/antagonist of the Ang-1/Tie2 axis, causing vascular destabilisation and sensitising blood vessels to the effects of vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A synergistically drive vascular leakage, neovascularisation and inflammation, key components of retinal vascular diseases. Preclinical evidence suggests that modulating the Ang/Tie pathway restores vascular stabilisation and reduces inflammation. This review discusses how targeting the Ang/Tie pathway or applying Ang-2/VEGF-A combination therapy may be a valuable therapeutic strategy for restoring vascular stability and reducing inflammation in the treatment of retinal and choroidal vascular diseases.

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Section: Discussionmentioning

confidence: 99%

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Joussen

Ricci

Paris

et al. 2021

Eye

113

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“…The Fc portion of this antibody has been optimized to eliminate binding of neonatal Fc and Fcγ receptors, decreasing both inflammation and systemic exposure. The results thus far have been promising, while Phase III trials have yet to be published, inflammation associated with faricimab in Phase II trials have been comparable to rates seen with ranibizumab [ 53 , 54 ].…”

Section: Putative Causative Factors Of Acute Onset Sterile Inflammationmentioning

confidence: 99%

Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review

et al. 2021

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Background Intraocular inflammation is an uncommon but potentially vision-threatening adverse event related to anti-VEGF therapy. This is of increasing importance given both the volume of injections performed, as well as the increased prevalence of inflammation seen with newer anti-VEGF agents. Brolucizumab, the newest anti-VEGF agent, has been associated with an inflammatory retinal vasculitis and the underlying mechanism is unclear. Reviewing potential mechanisms and clinical differences of intraocular inflammation may assist clinicians and scientists in reducing the risk of these events in the future. Observations Two types of inflammation are seen with intravitreal injections, acute onset sterile inflammation and delayed onset inflammatory vasculitis. Acute onset inflammation can be subcategorized into subclinical anterior chamber inflammation and sterile uveitis/endophthalmitis. Subclinical anterior chamber inflammation can occur at rates as high as 19% after intravitreal anti-VEGF injection. Rates of sterile uveitis/endophthalmitis range from 0.05% to 4.4% depending on the anti-VEGF agent. Inflammatory vasculitis is only associated with brolucizumab and occurred in 3.3% of injections according to the post hoc review of the HAWK/HARRIER data. In addition, silicone oil from syringes can induce immunogenic protein aggregates. Agitation of the syringe, freeze thawing, shipping and improper storage prior to injection may increase the amount of silicone oil released from the syringe. Conclusion The main factors which play a role in intraocular inflammation after anti-VEGF injection can be divided into three causes: patient-specific, medication-specific and delivery-specific. The majority of clinically significant inflammation seen after intravitreal injection is an acute onset inflammatory response with most patients recovering baseline VA in 3–5 weeks. The presence of pain, hypopyon, severe anterior chamber reaction, hyperemia and significant vision loss may help distinguish infectious from non-infectious etiologies of post injection inflammation. Avoiding temperature fluctuation, mechanical shock, agitation during transport and handling of syringes/drugs, and the use of SO-free syringes may help minimize intraocular inflammation. While a definitive mechanism has not yet been established, current knowledge of the clinical presentation and vitreous histopathology of brolucizumab-retinal vasculitis favors an auto-immune type IV hypersensitivity reaction.

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“…Although targeting VEGF continues to be the mainstay of therapy, as discussed above, there are numerous pathways and targets involved in the development of macular edema in retinal diseases. Research is ongoing into investigational drugs that can utilize these alternative pathways including angiopoietin and CCR3 [ 172 , 173 , 174 ]. Such pathways could provide therapeutic options that can be used alone or in combination with anti-VEGF to potentially improve effectiveness or prolong duration of response [ 175 ].…”

Section: Future Considerations—ranibizumab Port Delivery Systemmentioning

confidence: 99%

Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options

Wallsh

Gallemore

2021

Cells

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Anti-vascular endothelial growth factor (anti-VEGF) therapy currently plays a central role in the treatment of numerous retinal diseases, most notably exudative age-related macular degeneration (eAMD), diabetic retinopathy and retinal vein occlusions. While offering significant functional and anatomic benefits in most patients, there exists a subset of 15–40% of eyes that fail to respond or only partially respond. For these cases, various treatment options have been explored with a range of outcomes. These options include steroid injections, laser treatment (both thermal therapy for retinal vascular diseases and photodynamic therapy for eAMD), abbreviated anti-VEGF treatment intervals, switching anti-VEGF agents and topical medications. In this article, we review the effectiveness of these treatment options along with a discussion of the current research into future directions for anti-VEGF-resistant eyes.

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Safety and Efficacy of Different Doses and Regimens of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration

Cited by 98 publications

References 37 publications

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review

Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options

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