9月21日，FDA批准阿柏西普注射液（Eylea）用于视网膜中央静脉阻塞（CRVO）后黄斑水肿。去年11月，该药被批准用于湿性年龄相关性黄斑变性。今年8月，阿柏西普的另一种形式（Zaltrap）也被批准用于转移性结直肠癌。
作为一种血管生成抑制剂，阿柏西普可以结合VEGF-A型和B型以及胎盘生长因子，因此比其它的抗血管生成药物比如贝伐单抗作用更广泛。FDA所作的决议是基于COPERNICUS 和GALILEO的3期临床试验。与对照组相比，阿柏西普注射组2年内视力提高程度更高。
推荐剂量为每4周玻璃体内注射2mg，一旦出现眼内炎或视网膜脱离之类并发症的迹象，患者应立即报告。阿柏西普和其它玻璃体内注射的VEGF抑制剂均有引起动脉血栓栓塞的危险。
禁忌症为眼或眼周感染、活动性眼内炎症、超敏性。
美国食品药品监督管理局药物评价和研究中心抗微生物产品办公室主任Edward Cox, M.D., M.P.H说：“Eylea 对成年湿性AMD是一个重要的治疗选择”“它是潜在失明疾病和新治疗选择的可供利用是重要的。”
最常见不良反应为眼痛、眼结膜出血、白内障、玻璃体脱离、玻璃体漂浮物、眼压增高。
EYLEA - aflibercept injection, solution
Regeneron Pharmaceuticals, Inc.
EYLEA™ (aflibercept) Injection
For Intravitreal Injection
Initial U.S. Approval: 2011
INDICATIONS AND USAGE
EYLEA is indicated for the treatment of patients with Neovascular (Wet) Age-Related Macular Degeneration (AMD). (1)
DOSAGE AND ADMINISTRATION
•For ophthalmic intravitreal injection only. (2.1)
•The recommended dose for EYLEA is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (monthly) for the first 3 months, followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). (2.2)
•Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks. (2.2)
DOSAGE FORMS AND STRENGTHS
40 mg/mL solution for intravitreal injection in a single-use vial (3)
CONTRAINDICATIONS
•Ocular or periocular infection (4.1)
•Active intraocular inflammation (4.2)
•Hypersensitivity (4.3)
WARNINGS AND PRECAUTIONS
•Endophthalmitis and retinal detachments may occur following intravitreal injections. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. (5.1)
•Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection. (5.2)
ADVERSE REACTIONS
The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure. (6.2)
To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-855-395-3248 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Revised: 11/2011 

Regeneron Announces FDA Approval of EYLEA™ (aflibercept) Injection for the Treatment of Wet Age-Related Macular Degeneration
EYLEA is the only FDA-approved treatment for wet AMD labeled for less than monthly dosing that demonstrated clinical equivalence to the monthly standard of care
Regeneron to host conference call on November 18, at 6:30 p.m. Eastern Time
Tarrytown, NY (November 18, 2011) /PRNewswire/ — Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) today announced that the U.S. Food and Drug Administration (FDA) 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 milligrams (mg) every four weeks (monthly) for the first 12 weeks, followed by 2 mg every eight weeks (2 months).
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.
“The approval of EYLEA offers a much needed new treatment option for patients with wet AMD,” said Jeffrey Heier, M.D., a clinical ophthalmologist and retinal specialist at Ophthalmic Consultants of Boston, Assistant Professor of Ophthalmology at Tufts School of Medicine, and Chair of the Steering Committee for the VIEW 1 trial. “EYLEA offers the potential of achieving the efficacy we’ve come to expect from current anti-VEGF agents, but with less frequent injections and monitoring. This may reduce the need for costly and time-consuming monthly office visits for patients and their caregivers.”
“This approval is an important step forward for Regeneron and for patients suffering with wet AMD, the most common cause of blindness in the U.S. in older adults,” said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. “We thank the patients and clinical investigators who participated in our clinical studies, the FDA, and the Regeneron employees who helped make this day possible. Now that EYLEA is approved, we plan to make EYLEA available to patients within the next few days.”
About EYLEA™ (aflibercept) Injection
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, known in the scientific literature as VEGF Trap-Eye, 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 indicated for the treatment of patients with neovascular age-related macular degeneration (wet AMD). 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.
The recommended dose for EYLEA is 2 mg administered by intravitreal injection every four weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg once every eight weeks (2 months). Although EYLEA may be dosed as frequently as 2 mg every four weeks (monthly), additional efficacy was not demonstrated when EYLEA was dosed every four weeks compared to every eight weeks.
There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors, including EYLEA, 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 EYLEA and include endophthalmitis, traumatic cataract, and increased intraocular pressure.
About the VIEW 1 and VIEW 2 Clinical Studies
The safety and efficacy of EYLEA 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 EYLEA) 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) EYLEA administered 2 mg every eight weeks following three initial monthly doses (EYLEA 2Q8); 2) EYLEA administered 2 mg every four weeks (EYLEA 2Q4); 3) EYLEA 0.5 mg administered every four weeks (EYLEA 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 the EYLEA™ (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.
Select results of the VIEW 1 and VIEW 2 studies as described in the full Prescribing Information for the EYLEA 2 mg every four weeks and EYLEA 2 mg every eight weeks dosing groups as compared to ranibizumab dosed monthly group are shown below.
BCVA = Best Corrected Visual Acuity; CI = Confidence Interval; ETDRS = Early Treatment Diabetic Retinopathy Study; LOCF = Last Observation Carried Forward (baseline values are not carried forward); 95.1% confidence intervals were presented to adjust for safety assessment conducted during the study.
a After treatment initiation with 3 monthly doses
b EYLEA group minus the ranibizumab group
IMPORTANT SAFETY INFORMATION
EYLEA™ (aflibercept) Injection 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.
Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately.
There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors, including EYLEA, 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 EYLEA including endophthalmitis, traumatic cataract, and increased intraocular pressure.
The most common adverse reactions (greater than or equal to 5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.
Please see the full Prescribing Information for EYLEA, available online at www.regeneron.com/EYLEA-fpi.pdf.
About the EYLEA™ (aflibercept) Injection Global Collaboration
Regeneron is collaborating with Bayer HealthCare on the global development of EYLEA. Bayer submitted an application for marketing authorization in Europe for wet AMD in June 2011.
Bayer HealthCare will market EYLEA outside the United States, where the companies will share equally the profits from any future sales of EYLEA. Regeneron maintains exclusive rights to EYLEA in the United States.
About Wet AMD
Age-related macular degeneration (AMD) is a leading cause of acquired blindness. Macular degeneration is diagnosed as either dry (non-exudative) or wet (exudative). In wet AMD, new blood vessels grow beneath the retina and leak blood and fluid. This leakage causes disruption and dysfunction of the retina creating distortion and/or blind spots in central vision. Wet AMD is the leading cause of blindness for people over the age of 65 in the U.S. and Europe.