Perspective
Aflibercept for Age-Related Macular Degeneration: A Game-Changer or Quiet Addition?

https://doi.org/10.1016/j.ajo.2012.04.020Get rights and content

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.

Section snippets

Preclinical and Oncology Trials

The development of our currently used anti-VEGF drugs was based on a different long-term therapeutic strategy. Whereas bevacizumab was developed with a long systemic residence time exclusively for the systemic treatment of advanced cancers, ranibizumab was designed to have a short systemic clearance half-life by removing the Fc fragment from the parent IgG molecule, and its affinity for VEGF was enhanced by changing 5 of its amino acids, thereby optimizing it for the intraocular treatment of

Ophthalmology Trials

Based on a plausible biologic rationale for suspected efficacy and an acceptable safety profile in preclinical animal studies, aflibercept first was administered intravenously to patients with neovascular AMD in a placebo-controlled clinical trial.14 In 2 of the 5 patients receiving 3.0 mg/kg aflibercept, systemic toxicity developed (1 patient had grade 2 proteinuria and 1 patient had grade 4 hypertension). A subsequent phase 1 study of intravitreal aflibercept showed that up to 4-mg dosing

Drug and Treatment Regimens

In 2008, bevacizumab was used for 60% of the anti-VEGF injections in Medicare-fee-for-service beneficiaries with exudative AMD.20 In 2011, the Patterns and Trends Survey by the American Society of Retina Specialists reported that 70% of retina specialists used bevacizumab compared with ranibizumab for exudative AMD. The preference for off-label bevacizumab was influenced by its low cost and the perception that its efficacy and safety were similar to ranibizumab, which was confirmed by the

References (22)

  • M.W. Stewart

    Aflibercept (VEGF-Trap): the next anti-VEGF drug

    Inflamm Allergy Drug Targets

    (2011)
  • Cited by (0)

    View full text