Eylea injection for the treatment of wet age-related macular degeneration


The FDA ( Food and Drug Administration ) has approved Eylea ( Aflibercept ) injection, known in the scientific literature as VEGF Trap-Eye, for the treatment of patients with neovascular ( wet ) age-related macular degeneration ( AMD ) at a recommended dose of 2 mg every four weeks for the first 12 weeks, followed by 2 mg every eight weeks.
The approval of Eylea was granted under a Priority Review, a designation that is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. This approval was based upon the results of two phase 3 clinical studies. In these studies, Eylea dosed every eight weeks, following three initial monthly injections, was clinically equivalent to the standard of care, Lucentis ( Ranibizumab injection ) dosed every four weeks, as measured by the primary endpoint of maintenance of visual acuity ( less than 15 letters of vision loss on an eye chart ) over 52 weeks. The most common adverse reactions ( frequency of 5% or more ) reported in patients receiving Eylea were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure. The adverse event profile was similar to that seen with Ranibizumab.

Vascular endothelial growth factor ( VEGF ) is a naturally occurring protein in the body. Its normal role in a healthy organism is to trigger formation of new blood vessels ( angiogenesis ) supporting the growth of the body's tissues and organs. However, in certain diseases, such as wet age-related macular degeneration, it is also associated with the growth of abnormal new blood vessels in the eye, which exhibit abnormal increased permeability that leads to edema. Scarring and loss of fine-resolution central vision often results.

Eylea is a recombinant fusion protein, consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 and formulated as an iso-osmotic solution for intravitreal administration. Eylea acts as a soluble decoy receptor that binds VEGF-A and placental growth factor ( PlGF ) and thereby can inhibit the binding and activation of these cognate VEGF receptors.

Eylea is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to Aflibercept or to any of the excipients in Eylea.

There is a potential risk of arterial thromboembolic events following use of intravitreal VEGF inhibitors, including Aflibercept, defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death ( including deaths of unknown cause ). The incidence of ATEs with Eylea in clinical trials was low ( 1.8% ).

Serious adverse reactions related to the injection procedure have occurred in less than 0.1% of intravitreal injections with Aflibercept and include endophthalmitis, traumatic cataract, and increased intraocular pressure.

The safety and efficacy of Aflibercept were assessed in two randomized, multi-center, double-masked, active-controlled studies in patients with wet AMD. A total of 2412 patients were treated and evaluable for efficacy ( 1817 with Aflibercept ) in the two studies ( VIEW 1 and VIEW 2 ). In each study, patients were randomly assigned in a 1:1:1:1 ratio to one of four dosing regimens: 1) Aflibercept administered 2 mg every eight weeks following three initial monthly doses ( Aflibercept 2Q8 ); 2) Aflibercept administered 2 mg every four weeks (Aflibercept 2Q4 ); 3) Aflibercept 0.5 mg administered every four weeks ( Aflibercept 0.5Q4 ); and 4) Ranibizumab administered 0.5 mg every four weeks ( Ranibizumab 0.5Q4 ). Patient ages ranged from 49 to 99 years with a mean of 76 years.

In both studies, the primary efficacy endpoint was the proportion of patients who maintained vision, defined as losing fewer than 15 letters of visual acuity at week 52 compared to baseline. Data are available through week 52. Both Aflibercept injection 2Q8 and 2Q4 dosing groups were shown to have efficacy that was clinically equivalent to the Ranibizumab 0.5Q4 group for the primary endpoint.

Source: Regeneron, 2011

XagenaMedicine2011


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