后生可畏，拜耳眼科药物Eylea第4个适应症获欧盟批准

拜耳（Bayer）及合作伙伴再生元（Regeneron）近日宣布，眼科药物（aflibercept，阿柏西普注射液）在欧盟收获第4个适应症。欧盟委员会（EC）已批准Eylea用于视网膜静脉阻塞继发黄斑水肿（RVO-ME）的治疗，包括视网膜分支静脉阻塞继发黄斑水肿（BRVO-ME）及先前已获批的视网膜中央静脉阻塞继发黄斑水肿（CRVO-ME）。建议的治疗方法为：起始治疗时每周注射一次直至达到最大视力和/或无疾病活动迹象；之后，以一种“治疗-延长”方案继续治疗，逐渐延长治疗时间间隔，以维持稳定的视觉和/或解剖学结果。在欧盟，Eylea已获批的另外3个适应症为：湿性年龄相关性黄斑变性（wet-AMD），视网膜中央静脉阻塞继发黄斑水肿（CRVO-ME），糖尿病性黄斑水肿（DME）。

Eylea新适应症的获批，基于一项为期52周的双盲、随机、主动控制III期研究（VIBRANT）的结果。该研究在视网膜分支静脉阻塞（BRVO）继发黄斑水肿（ME）患者中开展，Eylea治疗组每月注射2mg剂量Eylea，对照组接受激光光凝治疗。数据表明，在研究的24周，Eylea治疗组有更高比例的患者最佳矫正视力（BCVA）取得了至少15个字母的改善（53% vs 27%，p＜0.001），达到了研究的主要终点。此外，Eylea治疗组BCVA从基线平均改善达17.0个字母，对照组为6.9个字母，达到了研究的关键次要终点（p＜0.0001）。

目前，眼科治疗领域，拜耳正与罗氏及诺华展开激烈竞争。Eylea于2011年上市，但近年来发展势头迅猛，适应症个数及全球销售一再刷新并连续多次超过业界预期，已对罗氏和诺华眼科药物Lucentis（2006年上市）形成严峻挑战。此外，根据拜耳2014年10月公布的一项研究，用于治疗糖尿病性黄斑水肿（DME）时，Eylea击败了Lucentis和Avastin，该项研究结果使得Eylea在DME领域更具影响力。

不过，本月中旬，Lucentis率先赢得FDA祝福，拿下糖尿病性视网膜病变（DR）适应症，标志着对Eylea强有力的反击，该适应症也是Lucentis在美国市场收获的第4个适应症。其他3个适应症分别为：糖尿病性黄斑水肿（DME，2006年）、视网膜静脉阻塞继发黄斑水肿（RVO-ME，2010年）和湿性年龄相关性黄斑变性（wet-AMD，2012）。

英文原文：

Bayer Receives EU Approval for EYLEA for the Treatment of Retinal Vein Occlusion

Berlin, February 26, 2015 – Bayer HealthCare announced today that EYLEA? (aflibercept solution for injection into the eye) has been approved by the European Commission for the treatment of patients with visual impairment due to macular edema secondary to retinal vein occlusion (RVO). This new indication includes macular edema following branch retinal vein occlusion (BRVO) in addition to the previously-approved indication of macular edema secondary to central retinal vein occlusion in adults (CRVO). The recommended treatment approach is to initiate therapy with one injection per month until maximum visual acuity is achieved and/or there are no signs of disease activity. Treatment may then be continued with a “treat and extend” regimen with gradually increased treatment intervals to maintain stable visual and/or anatomic outcomes.

“RVO is a chronic disease that requires early and ongoing management to obtain the best possible vision, which is critical as many patients are still of working-age,” said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. “This new therapeutic approach allows physicians to individualize therapy for each patient, maximizing time between treatments. This reduces the treatment burden on patients, physicians and their clinics."

The approval is based on positive results from the double-masked, randomized, active-controlled phase 3 VIBRANT study in patients with visual impairment due to macular edema secondary to BRVO. The primary endpoint was the proportion of subjects who gained at least 15 letters in best corrected visual acuity (BCVA) from baseline at week 24, as measured on the Early Treatment Diabetic Retinopathy Scale (ETDRS) eye chart, a standard chart used in research to measure visual acuity. More than half of the patients who were treated with aflibercept solution for injection gained at least three lines of vision.

About Retinal Vein Occlusion
Retinal vein occlusion (RVO) includes branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). RVO is a chronic eye condition that can lead to sudden vision loss and is second only to diabetic retinopathy as the most frequent cause of visual loss from diseases affecting the blood vessels of the retina. While each patient experiences RVO differently, all patients are at risk for vision loss which can impact their ability to participate in everyday activities and may cause significant financial burden to patients, their families as well as broader society. RVO has a significant global impact with an estimated 16.4 million people affected worldwide, including around 13.9 million with BRVO and 2.5 million with CRVO.

RVO is the result of a blockage in a blood vessel of the retina, the light sensitive part of the eye. In CRVO, the blockage occurs in the main retinal vein at the optic nerve. In BRVO, the blockage occurs in one of the branch retinal veins. If a blockage in any of the retinal veins (central or branch) is not resolved, it can result in a number of complications. The most common reason for vision impairment in patients with RVO is macular edema, swelling of the macula, which is the central portion of the retina responsible for seeing fine details.

About VEGF and EYLEA? (aflibercept solution for injection into the eye)
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. It is also associated with the growth of abnormal new blood vessels in the eye, which exhibit abnormal increased permeability that leads to edema.

Aflibercept solution for injection 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. Aflibercept acts as a soluble decoy receptor that binds VEGF-A and placental growth factor (PlGF) and thereby can inhibit the binding and activation of their cognate VEGF receptors.

Aflibercept solution for injection into the eye has been approved under the brand name EYLEA? in more than 80 countries for the treatment of patients with neovascular age-related macular degeneration (wet AMD) and around 40 countries for the treatment of visual impairment due to macular edema secondary to central retinal vein occlusion. EYLEA is also approved for the treatment of diabetic macular edema (DME) in over 40 countries. Over three million doses of EYLEA have been administered since launch worldwide. In Japan, EYLEA has been additionally approved for the treatment of myopic choroidal neovascularization and an application for marketing authorization has also been submitted for the treatment of macular edema secondary to BRVO. In the U.S., EYLEA is already approved for the treatment of RVO.

Bayer HealthCare and Regeneron Pharmaceuticals, Inc. are collaborating on the global development of EYLEA. Regeneron maintains exclusive rights to EYLEA in the U.S. Bayer HealthCare licensed the exclusive marketing rights outside the U.S., where the companies share equally the profits from sales of EYLEA, except for Japan where Regeneron receives a percentage of net sales.