Aflibercept

Compound Name:AfliberceptMolecular Target:VEGF, PIGFMolecular Structure:Fusion protein: IgG Fc, and ligand binding domains of VEGFR-1, VEGFR-2Licensed Indication:Wet age-related macular edema; Macular edema following central retinal vein occlusionManufacturer and/or Distributor:Regeneron/Sanofi-AventisInitial FDA Approval2011SummaryAflibercept is a fusion protein construct consisting of the Fc portion of human IgG linked to the ligand binding domains of the VEGRF-1 and VEGRF-2 receptors. It binds with high affinity to (vascular endothelial growth factor) VEGF-A, VEGF-B, (placental growth factor) PlGF-1 and PlGF-2, and inhibits neovascularization and vascular permeability. It is the same medicine as ziv-aflibercept (Zaltrap®), which is marketed for treatment of metastatic colorectal cancer.

 Aflibercept was first approved in 2011 for the treatment of neovascular (wet) age-related macular edema. Two phase III trials showed the aflibercept was not inferior to ranibizumab in maintaining visual acuity at 52 weeks. In 2012, an indication was added for macular edema following central retinal vein occlusion. Two phase III sham-injection controlled trials showed superior gain in vision with aflibercept at 24 weeks and at 52 weeks.
In September 2014, based on positive results in two phase III trials (VIVID-DME and VISTA-DME) the FDA
has granted first Eylea injection Breakthrough Therapy designation and in March 2015 approved its use for the treatment of diabetic retinopathy in patients with diabetic macular edema. Since aflibercept is administered intravitreally, rather than systemically as is ziv-aflibercept, its major safety concerns are more limited. They include endophthalmitis, retinal detachments, increased intraocular pressure, as well as arterial thrombotic events such as strokes or myocardial infarctions. It comes under Pregnancy Category C.References

Package Insert: http://www.regeneron.com/Eylea/eylea-fpi.pdf



1. Brown D, Heier J, Clark W, Boyer D, Vitti R, Berliner A, et al. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. American journal of ophthalmology. 2013;155(3):429-75032704. http://www.ncbi.nlm.nih.gov/pubmed/23218699

2. Browning D, Kaiser P, Rosenfeld P, Stewart M. Aflibercept for age-related macular degeneration: a game-changer or quiet addition? American journal of ophthalmology. 2012;154(2):222-226. http://www.ncbi.nlm.nih.gov/pubmed/22813448

3. Clarke J, Hurwitz H. Ziv-aflibercept: binding to more than VEGF-A--does more matter? Nature reviews Clinical oncology. 2013;10(1):10-11. http://www.ncbi.nlm.nih.gov/pubmed/23149898

4. Evoy K, Abel S. Aflibercept: newly approved for the treatment of macular edema following central retinal vein occlusion. The Annals of pharmacotherapy. 2013;47(6):819-827. http://www.ncbi.nlm.nih.gov/pubmed/23673531

5. Heier J, Brown D, Chong V, Korobelnik J-F, Kaiser P, Nguyen Q, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548. http://www.ncbi.nlm.nih.gov/pubmed/24084500

6. Ho V, Yeh S, Olsen T, Bergstrom C, Yan J, Cribbs B, et al. Short-term outcomes of aflibercept for neovascular age-related macular degeneration in eyes previously treated with other vascular endothelial growth factor inhibitors. American journal of ophthalmology. 2013;156(1):23-2800. http://www.ncbi.nlm.nih.gov/pubmed/23664153

7. Ohr M, Kaiser P. Aflibercept in wet age-related macular degeneration: a perspective review. Therapeutic advances in chronic disease. 2012;3(4):153-161. http://www.ncbi.nlm.nih.gov/pubmed/22965962

8. Virgili G, Parravano M, Menchini F, Evans JR. Anti-vascular endothelial growth factor for diabetic macular oedema. Cochrane Database Syst Rev. 2014 Oct 24;10:CD007419. http://www.ncbi.nlm.nih.gov/pubmed/25342124

9. Rahimy E, Shahlaee A, Khan MA, Ying GS, Maguire JI et al. Conversion to aflibercept after prior anti-VEGF therapy for persistent diabetic macular edema. Am J Ophthalmol. 2015 Dec 31. http://www.ncbi.nlm.nih.gov/pubmed/26748058

10. Heier JS, Bressler NM, Avery RL, Bakri SJ, Boyer DS et al. Comparison of Aflibercept, Bevacizumab, and Ranibizumab for Treatment of Diabetic Macular Edema: Extrapolation of Data to Clinical Practice. JAMA Ophthalmol. 2016 Jan 1;134(1):95-9. http://www.ncbi.nlm.nih.gov/pubmed/26512939

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