Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials

Heier, Jeffrey S.; Khanani, Arshad M.; Ruiz, Carlos Quezada; Basu, Karen; Ferrone, Philip J.; Brittain, Christopher; Figueroa, Marta S.; Lin, Hugh; Holz, Frank G.; Patel, Vaibhavi; Lai, Timothy Y Y; Silverman, David G.; Regillo, Carl D.; Swaminathan, Balakumar; Viola, Francesco; Cheung, Chui Ming Gemmy; Wong, Tien Yin

doi:10.1016/s0140-6736(22)00010-1

Cited by 335 publications

(242 citation statements)

References 28 publications

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“…Now, several bispecific proteins are in clinical development, such as faricimab (RG7716, Roche) ( 17 , 58 ) and ABBV642 ( 59 ), targeting VEGF together with other angiogenic factors. Recently published data have highlighted the 1-year results from two phase 3 clinical trials, supporting the efficacy and potentially extend treatment interval of faricimab in patients with nAMD ( 60 ).…”

Section: Discussionmentioning

confidence: 95%

Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy

Yang

Jia

et al. 2022

Sci. Transl. Med.

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Antiangiogenesis therapies targeting vascular endothelial growth factor (VEGF) have revolutionized the treatment of neovascular ocular diseases, including neovascular age-related macular degeneration (nAMD). Compelling evidence has implicated the vital role of complement system dysregulation in AMD pathogenesis, implying it as a potential therapeutic strategy for geographic atrophy in dry AMD and to enhance the efficacy of anti-VEGF monotherapies in nAMD. This study reports the preclinical assessment and phase 1 clinical outcomes of a bispecific fusion protein, efdamrofusp alfa (code: IBI302), which is capable of neutralizing both VEGF isoforms and C3b/C4b. Efdamrofusp alfa showed superior efficacy over anti-VEGF monotherapy in a mouse laser-induced choroidal neovascularization (CNV) model after intravitreal delivery. Dual inhibition of VEGF and the complement activation was found to further inhibit macrophage infiltration and M2 macrophage polarization. Intravitreal efdamrofusp alfa demonstrated favorable safety profiles and exhibited antiangiogenetic efficacy in a nonhuman primate laser-induced CNV model. A phase 1 dose-escalating clinical trial (NCT03814291) was thus conducted on the basis of the preclinical data. Preliminary results showed that efdamrofusp alfa was well tolerated in patients with nAMD. These data suggest that efdamrofusp alfa might be effective for treating nAMD and possibly other complement-related ocular conditions.

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Section: Discussionmentioning

confidence: 95%

Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy

Yang

Jia

et al. 2022

Sci. Transl. Med.

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“…This led to speculation that ANGPT2 expression may contribute to the modest response of some patients with nvAMD to anti-VEGF therapy ( 26 , 27 ). Consequently, there are ongoing and recently completed clinical trials examining the safety and efficacy of therapies directly or indirectly targeting ANGPT2 and its downstream receptor, TIE2, in patients with nvAMD ( 28 , 29 ). To determine if ANGPT2 expression influenced the response of patients with nvAMD to anti-VEGF therapy, we examined levels of ANGPT2 in patients treated with anti-VEGF therapy using the TEP/M protocol.…”

Section: Resultsmentioning

confidence: 99%

ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization

Yu¹,

Dinabandhu²,

Sanchez³

et al. 2022

JCI Insight

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Most patients with neovascular age-related macular degeneration (nvAMD), the leading cause of severe vision loss in elderly US citizens, respond inadequately to current therapies targeting a single angiogenic mediator, vascular endothelial growth factor (VEGF). Here, we report that aqueous fluid levels of a second vasoactive mediator, angiopoietin-like 4 (ANGPTL4), can help predict the response of patients with nvAMD to anti-VEGF therapies. ANGPTL4 expression was higher in patients who required monthly treatment with anti-VEGF therapies compared with patients who could be effectively treated with less-frequent injections. We further demonstrate that ANGPTL4 acts synergistically with VEGF to promote the growth and leakage of choroidal neovascular (CNV) lesions in mice. Targeting ANGPTL4 expression was as effective as targeting VEGF expression for treating CNV in mice, while simultaneously targeting both was more effective than targeting either factor alone. To help translate these findings to patients, we used a soluble receptor that binds to both VEGF and ANGPTL4 and effectively inhibited the development of CNV lesions in mice. Our findings provide an assay that can help predict the response of patients with nvAMD to anti-VEGF monotherapy and suggest that therapies targeting both ANGPTL4 and VEGF will be a more effective approach for the treatment of this blinding disease.

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“…Table 4 summarizes the benefits, risks, and recommendations for each routine assessment procedures done prior to IVT. Newer intravitreal drugs or drug delivery systems such as faricimab and port-delivery systems that are being currently developed aims to increased injection intervals with the potential to further reduce the number of clinic visits [ 10 – 12 ].…”

Section: Discussionmentioning

confidence: 99%

Are intravitreal injections essential during the COVID-19 pandemic? Global preferred practice patterns and practical recommendations

Tan

Schwartz²,

Anaya³

et al. 2022

Int J Retin Vitr

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Tertiary outpatient ophthalmology clinics are high-risk environments for COVID-19 transmission, especially retina clinics, where regular follow-up is needed for elderly patients with multiple comorbidities. Intravitreal injection therapy (IVT) for chronic macular diseases, is one of the most common procedures performed, associated with a significant burden of care because of the vigorous treatment regimen associated with multiple investigations. While minimizing the risk of COVID-19 infection transmission is a priority, this must be balanced against the continued provision of sight-saving ophthalmic care to patients at risk of permanent vision loss. This review aims to give evidence-based guidelines on managing IVT during the COVID-19 pandemic in common macular diseases such as age-related macular degeneration, diabetic macula edema and retinal vascular disease and to report on how the COVID-19 pandemic has affected IVT practices worldwide.To illustrate some real-world examples, 18 participants in the International Retina Collaborative, from 15 countries and across four continents, were surveyed regarding pre- and during- COVID-19 pandemic IVT practices in tertiary ophthalmic centers. The majority of centers reported a reduction in the number of appointments to reduce the risk of the spread of COVID-19 with varying changes to their IVT regimen to treat various macula diseases. Due to the constantly evolving nature of the COVID-19 pandemic, and the uncertainty about the normal resumption of health services, we suggest that new solutions for eye healthcare provision, like telemedicine, may be adopted in the future when we consider new long-term adaptations required to cope with the COVID-19 pandemic.

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Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials

Cited by 335 publications

References 28 publications

Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy

Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy

ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization

Are intravitreal injections essential during the COVID-19 pandemic? Global preferred practice patterns and practical recommendations

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