Aflibercept for age-related macular degeneration: a game-changer or quiet addition?

Abstract

PURPOSE:

To describe the pharmacokinetics, preclinical studies, and clinical trials of the newly approved anti-vascular endothelial growth factor (VEGF) drug aflibercept (Eylea (VEGF Trap-Eye); Regeneron; and Bayer).

DESIGN:

Review with editorial commentary.

METHODS:

A review of the medical literature and pertinent Internet postings combined with analysis of key studies with expert opinion regarding the use of aflibercept for the treatment of exudative age-related macular degeneration.

RESULTS:

Aflibercept, a fusion protein with binding domains from native VEGF receptors, binds VEGF-A, VEGF-B, and placental growth factors 1 and 2 with high affinity. Preclinical ophthalmologic studies demonstrated that aflibercept suppresses choroidal neovascularization in several animal models. The results of phase 1 and 2 trials showed excellent short-term suppression of choroidal neovascularization in patients with exudative age-related macular degeneration and suggested a longer durability of aflibercept compared with other anti-VEGF drugs. The pivotal phase 3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration 1 and 2 trials showed that monthly and bimonthly aflibercept were noninferior to monthly ranibizumab at preventing vision loss (< 15-letter loss) with comparable vision gains and safety. Year 2 treatment involved monthly pro re nata injections with required injections every 3 months and maintained vision gains from the first year, with an average of 4.2 injections of aflibercept and 4.7 injections of ranibizumab.

CONCLUSIONS:

Aflibercept promises to deliver excellent visual outcomes for exudative age-related macular degeneration patients while undergoing fewer injections compared with ranibizumab. With a wholesale cost of $1850 per dose, the cost per patient with aflibercept treatment promises to be lower than with ranibizumab.

• Authors: David J Browning, Peter K Kaiser, Philip J Rosenfeld, Michael W Stewart
• Journal: American journal of ophthalmology (Am J Ophthalmol) Vol. 154 Issue 2 Pg. 222-6 (Aug 2012) ISSN: 1879-1891 [Electronic] United States
• PMID: 22813448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Recombinant Fusion Proteins
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• aflibercept
• Receptors, Vascular Endothelial Growth Factor

Topics

• Angiogenesis Inhibitors (pharmacokinetics, pharmacology, therapeutic use)
• Animals
• Clinical Trials as Topic
• Drug Approval
• Drug Evaluation, Preclinical
• Humans
• Macular Degeneration (drug therapy)
• Receptors, Vascular Endothelial Growth Factor
• Recombinant Fusion Proteins (pharmacokinetics, pharmacology, therapeutic use)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)