PerspectiveAflibercept for Age-Related Macular Degeneration: A Game-Changer or Quiet Addition?
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)
- et al.
Comparing protein VEGF inhibitors: in vitro biological studies
Biochem Biophys Res Commun
(2011) - et al.
Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo
Am J Pathol
(2002) - et al.
Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts
Am J Pathol
(2004) - 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) - et al.
The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing
Ophthalmology
(2011) - et al.
Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration
Retina
(2006) - et al.
VEGF-Trap: a VEGF blocker with potent antitumor effects
Proc Natl Acad Sci U S A
(2002) - et al.
Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab
Angiogenesis
(2012) What are the half-lives of ranibizumab and aflibercept (VEGF Trap-eye) in human eyes?Calculations with a mathematical model
Eye Reports
(2011)- et al.
Predicted biological activity of intravitreal VEGF Trap
Br J Ophthalmol
(2008)