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Intravitreal Aflibercept (Eylea®): A Review of Its Use in Patients with Macular Oedema Secondary to Central Retinal Vein Occlusion

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Abstract

Aflibercept is a fully human, recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF) family members, including VEGF-A, VEGF-B and placental growth factor (P1GF), thereby inhibiting downstream signalling mediated by these ligands. Aflibercept binds all isoforms of VEGF-A with high affinity, and a markedly higher affinity than that of ranibizumab or bevacizumab. A formulation of aflibercept developed specifically for intravitreal injection (Eylea®) is approved for use in several countries for the treatment of patients with macular oedema secondary to central retinal vein occlusion (CRVO). In clinical trials (GALILEO and COPERNICUS) in patients with this condition, intravitreal aflibercept 2 mg every month improved best corrected visual acuity (BCVA), as measured by the proportion of study eyes with a gain of ≥15 Early Treatment Diabetic Retinopathy Study letters from baseline, significantly more than sham injections at week 24 (primary analysis). The significant improvements achieved with intravitreal aflibercept compared with sham in the first 6 months were maintained in the second 6 months with as-needed (prn) dosing and monthly monitoring. Continued prn dosing with a reduced monitoring frequency was associated with decreased improvements. More data are needed to confirm the optimal monitoring frequency for use with prn dosing, subsequent to initial monthly injections, in order to maintain long-term efficacy. Intravitreal aflibercept was generally well tolerated in clinical trials and there is little potential for systemic drug accumulation. Thus, intravitreal aflibercept is an effective and generally well tolerated agent that extends the options available for the treatment of macular oedema secondary to CRVO.

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References

  1. Stewart MW. The expanding role of vascular endothelial growth factor inhibitors in ophthalmology. Mayo Clin Proc. 2012;87(1):77–88.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Figueroa MS, Contreras I. Potential anti-vascular endothelial growth factor therapies for central retinal vein occlusion. Drugs. 2012;72(16):2063–71.

    Article  CAS  PubMed  Google Scholar 

  3. Rogers S, McIntosh RL, Cheung N, et al. The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology. 2010;117(2):313–9.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Evoy KE, Abel SR. Aflibercept: newly approved for the treatment of macular edema following central retinal vein occlusion. Ann Pharmacother. 2013;47(6):819–27.

    Article  PubMed  Google Scholar 

  5. Regeneron Pharmaceuticals Inc. Eylea® (aflibercept) injection: US prescribing information. 2014. http://www.regeneron.com/Eylea/eylea-fpi.pdf. Accessed 31 Mar 2014.

  6. European Medicines Agency. Eylea (aflibercept) solution for intravitreal injection: summary of product characteristics. 4 Sep 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002392/WC500135815.pdf. Accessed 31 Mar 2014.

  7. Frampton JE. Aflibercept for intravitreal injection: in neovascular age-related macular degeneration. Drugs Aging. 2012;29(10):839–46.

    Article  CAS  PubMed  Google Scholar 

  8. Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 2002;99(17):11393–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Papadopoulos N, Martin J, Ruan Q, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012;15(2):171–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008;92(5):667–8.

    Article  CAS  PubMed  Google Scholar 

  11. Ammar DA, Mandava N, Kahook MY. The effects of aflibercept on the viability and metabolism of ocular cells in vitro. Retina. 2013;33(5):1056–61.

    Article  CAS  PubMed  Google Scholar 

  12. Schnichels S, Hagemann U, Januschowski K, et al. Comparative toxicity and proliferation testing of aflibercept, bevacizumab and ranibizumab on different ocular cells. Br J Ophthalmol. 2013;97(7):917–23.

    Article  PubMed  Google Scholar 

  13. Saishin Y, Saishin Y, Takahashi K, et al. VEGF-TRAP(R1R2) suppresses choroidal vascularization and VEGF-induced breakdown of the blood-retinal barrier. J Cell Physiol. 2003;195:241–8.

    Article  CAS  PubMed  Google Scholar 

  14. Brown DM, Heier JS, Ciulla T, et al. Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. Ophthalmology. 2011;118(6):1089–97.

    Article  PubMed  Google Scholar 

  15. Christoforidis JB, Williams MM, Kothandaraman S, et al. Pharmacokinetic properties of intravitreal I-124-aflibercept in a rabbit model using PET/CT. Curr Eye Res. 2012;37(12):1171–4.

    Article  CAS  PubMed  Google Scholar 

  16. Holz FG, Roider J, Ogura Y, et al. VEGF Trap-Eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br J Ophthalmol. 2013;97(3):278–84.

    Article  PubMed  Google Scholar 

  17. Korobelnik JF, Holz FG, Roider J, et al. Intravitreal aflibercept injection for macular edema resulting from central retinal vein occlusion: one-year results of the phase 3 GALILEO study. Ophthalmology. 2014;121:202–8.

    Article  PubMed  Google Scholar 

  18. Ogura Y, Korobelnik JF, Roider J, et al. Eighteen-month results of the GALILEO study evaluating intravitreal aflibercept injection (IAI) for macular edema secondary to central retinal vein occlusion (CRVO) [abstract no. 4516]. 2013 Annual Meeting of the Association for Research and Vision in Ophthalmology; 5–9 May 2013; Seattle, WA.

  19. Boyer D, Heier J, Brown DM, et al. Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology. 2012;119(5):1024–32.

    Article  PubMed  Google Scholar 

  20. Brown DM, Heier JS, Clark WL, et al. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol. 2013;155(3):429–37.

    Article  CAS  PubMed  Google Scholar 

  21. Heier JS, Clark WL, Boyer DS, et al. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology. 2014 Mar. doi:10.1016/j.ophtha.2014.01.027.

  22. Stewart MW. Aflibercept (VEGF trap-eye): the newest anti-VEGF drug. Br J Ophthalmol. 2012;96(9):1157–8.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Chong V. Biological, preclinical and clinical characteristics of inhibitors of vascular endothelial growth factors. Ophthalmologica. 2012;227(Suppl 1):2–10.

    Article  CAS  PubMed  Google Scholar 

  24. Genetech Inc. Lucentis® (ranibizumab injection): US prescribing information. Feb 2014. http://www.gene.com/download/pdf/lucentis_prescribing.pdf. Accessed 31 Mar 2014.

  25. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537–48.

    Article  PubMed  Google Scholar 

  26. Heier JS, Campochiaro PA, Yau L, et al. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophtholmology. 2012;119:802–9.

    Article  Google Scholar 

  27. US National Institutes of Health. ClinicalTrials.gov. 2014. http://clinicaltrials.gov/. Accessed 6 Jan 2014.

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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Authors and Affiliations

  1. Adis, 41 Centorian Drive, Private Bag 65901 Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Lily P. H. Yang & Kate McKeage

Authors
  1. Lily P. H. Yang
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  2. Kate McKeage
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Corresponding author

Correspondence to Kate McKeage.

Additional information

The manuscript was reviewed by: D. Boyer, Retina-Vitreous Associates Medical Group, Los Angeles, CA, USA; V. Chong, Oxford Eye Hospital, Oxford University Hospitals, Oxford, UK; M. U. Saeed, The Sutton Eye Unit, Epsom and St Helier’s University Hospitals NHS Trust, London, UK; M. W. Stewart, Department of Ophthalmology, Mayo Clinic, Jacksonville, FL, USA.

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Yang, L.P.H., McKeage, K. Intravitreal Aflibercept (Eylea®): A Review of Its Use in Patients with Macular Oedema Secondary to Central Retinal Vein Occlusion. Drugs Aging 31, 395–404 (2014). https://doi.org/10.1007/s40266-014-0176-2

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  • DOI: https://doi.org/10.1007/s40266-014-0176-2

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