Regeneron Pharmaceuticals, Inc's Eylea

The FDA approved Eylea (aflibercept) injection for the treatment of neovascular age-related macular degeneration.

Regeneron Pharmaceuticals, Inc’s Eylea (aflibercept) Injection has received approval from the FDA for the treatment of neovascular (wet) age-related macular degeneration (AMD).¹ AMD affects the macula, causing central vision to deteriorate and impairing visual fine detail.²

The wet form occurs when new blood vessels grow beneath the retina and leak blood and fluid, leading to retinal disruption and dysfunction with subsequent vision loss.^2,3 An early symptom of wet AMD is when straight lines appear wavy.² Wet AMD is the most common cause of blindness in adults older than 65 years in the United States and Europe.³

Pharmacology and Pharmacokinetics

Vascular endothelial growth factor (VEGF) is a protein that helps to trigger formation of new blood vessels in healthy people. In some conditions, however, VEGF is associated with the abnormal growth of blood vessels in the eye. Eylea exerts its effect by acting as a soluble decoy receptor that binds to VEGF-A and placental growth factor, thus inhibiting the binding and activation of these cognate VEGF receptors.³

The mean C_max of free Eylea after a 2-mg intravitreal dose was 0.02 mcg/mL after 1 to 3 days. The free plasma concentration of Eylea after 2 weeks was undetectable. It does not accumulate in plasma when dosed repeatedly at 4-week intervals.¹

Dosage and Administration

Eylea should be given by opthalmic intravitreal injection only and should only be administered by a qualified physician. The initial dose is 2 mg by intravitreal injection every 4 weeks for the first 12 weeks, then 2 mg by intravitreal injection once every 8 weeks thereafter. Although Eylea can be given as often as 2 mg every 4 weeks, no additional benefit was found with the more frequent dosing interval.

Eylea is available as a 40-mg/mL solution in a single-use vial.¹

Clinical Trials

Eylea was evaluated for safety and efficacy in 2 randomized, multi-center, double-masked, active-controlled trials in 2412 patients with wet AMD. Patients were randomized to 1 of 4 dosing regimens in a 1:1:1:1 ratio: Eylea 2 mg every 8 weeks after 3 initial monthly doses, Eylea 2 mg every 4 weeks, Eylea 0.5 mg every 4 weeks, or ranibizumab 0.5 mg every 4 weeks. Patients ranged from 49 to 99 years with a mean age of 76 years.

The primary end point in both studies was the proportion of patients who maintained vision, which was defined as losing fewer than 15 letters of visual acuity at week 52 compared with baseline. Both Eylea 2 mg every 8 weeks and Eylea 2 mg every 4 weeks demonstrated efficacy that was clinically equivalent to the ranibizumab group for the primary end point.^1,3

Contraindications, Warnings, and Precautions

The use of Eylea is contraindicated in patients with ocular or periocular infection, active intraocular inflammation, or hypersensitivity to the active ingredient in Eylea or any of its components.

Endophthalmitis and retinal detachments have been reported after use of intravitreal injections, including Eylea. Patients experiencing any symptoms of endophthalmitis and/or retinal detachments should report them immediately and should be managed appropriately.

Increased intraocular pressure has been observed within 60 minutes of intraocular injections, including Eylea. Intraocular pressure and optic nerve perfusion should be monitored and managed appropriately. The use of intravitreal VEGF inhibitors, including Eylea, carries the potential risk of arterial thromboembolic events, such as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). In clinical trials, this risk during the first year was 1.8%.

Eylea is Pregnancy Category C and should only be used if its benefits outweigh the risks. It should not be used in mothers who are breast-feeding. Eylea has not been studied in pediatric patients.

The most commonly reported adverse events (≥5%) are conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.¹

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.

References

1. Eylea complete prescribing information. www.regeneron.com/Eylea/eylea-fpi.pdf. Accessed April 2012.

2. FDA approves Eylea for eye disorder in older people. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm280601.htm. Accessed March 2012.

3. Regeneron announces FDA approval of EYLEA™ (aflibercept) injection for the treatment of wet age-related macular degeneration. http://investor.regeneron.com/releasedetail.cfm?ReleaseID=625771. Accessed March 2012.