2015年1月24日讯 /生物谷BIOON/ --拜耳（Bayer）近日宣布，眼科药物（aflibercept，阿柏西普注射液）第4个适应症获得了欧洲药品管理局（EMA）人用医药产品委员会（CHMP）的支持。CHMP建议批准Eylea用于视网膜静脉阻塞（RVO）继发黄斑水肿（ME）的治疗，包括视网膜分支静脉阻塞（BRVO）继发黄斑水肿（ME）及先前已获批的视网膜中央静脉阻塞（CRVO）继发黄斑水肿（ME）。
CHMP的积极意见，是基于一项为期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个之母的改善（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）。
视网膜静脉阻塞（RVO）包括视网膜分支静脉阻塞（BRVO）和视网膜中央静脉阻塞（CRVO），在全球范围内估计有1640万患者，其中1390万BRVO，250万CRVO。
目前，眼科治疗领域，拜耳正与罗氏和诺华展开激烈竞争。拜耳的Eylea于2011年上市，近年来发展势头迅猛，适应症个数及全球销售额一再刷新，连续多次超过业界预期，在相关疾病领域已对罗氏和诺华眼科药物Lucentis（2006年上市）形成了严峻的挑战。根据2014年10月公布的一项研究，在治疗糖尿病性黄斑水肿（DME）时，Eylea击败了Lucentis和Avastin，使Eylea在DME领域更具影响力。另外，双方正在糖尿病性视网膜病变（DR）领域展开激烈竞争，FDA分别于2014年9月和12月授予Eylea和Lucentis治疗DR的突破性疗法认定。
目前，Eylea已获批的适应症包括：湿性年龄相关性黄斑变性（wet-AMD），视网膜中央静脉阻塞（CRVO），糖尿病性黄斑水肿（DME）。视网膜分支静脉阻塞（BRVO）继发黄斑水肿（ME）是Eylea在欧美市场的第4个新适应症申请。
关于Eylea：
Eylea是一种新型玻璃体内注射用VEGF抑制剂，是一种重组融合蛋白，由人体血管内皮细胞生长因子（VEFG）受体1和2的胞外区与人体免疫球蛋白G1的可结晶片段融合而成。Eylea作为VEGF家族各成员（包括VEGF-A）及胎盘生长因子（PIGF）的一种可溶性诱饵受体发挥作用，与这些因子具有极高的亲和力，从而抑制这些因子与同源VEGF受体的结合，因此Eylea可抑制异常的血管生成及渗漏。
目前，拜耳和Regeneron正在合作Eylea的全球开发。Regeneron保留Eylea在美国的独家权利，拜耳则授权获得该药在美国以外国家和地区的独家销售权，这2家公司将平分Eylea在未来销售的利润。
英文原文：Bayer Receives Recommendation for Approval for New Treatment Option with Aflibercept Solution for Injection in EU
CHMP recommends EU approval for the treatment of visual impairment due to Macular Edema Secondary to Retinal Vein Occlusion
Berlin, January 23, 2015 - Bayer HealthCare today announced that aflibercept solution for injection into the eye has been recommended for approval by the European Committee for Medicinal Products for Human Use (CHMP) for the treatment of patients with visual impairment due to macular edema secondary to retinal vein occlusion (RVO), which 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 (CRVO).
"Retinal vein occlusion is a common retinal vascular disorder with an estimated 16.4 million people affected worldwide, and it is a severe disease which is potentially blinding if not treated early and appropriately," said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. "Vision impairment and blindness impact not only patients through loss of independence, but also their families. Therefore, we hope to be able to offer patients suffering from vision impairment secondary to BRVO and their physicians this new treatment option shortly."
The positive CHMP recommendation is based on positive results from the double-masked, randomized, active-controlled phase 3 VIBRANT study in patients impacted by 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.
The previously approved indication of Macular Edema secondary to CRVO was based on data from the Phase 3 COPERNICUS and GALILEO studies. In both studies, the primary efficacy endpoint was the proportion of patients who gained at least 15 ETDRS letters of BCVA at 24 weeks compared to baseline on the ETDRS visual acuity charts.
About the Phase 3 VIBRANT Study
VIBRANT was a Phase 3, randomized, double-masked, active-controlled 52-week study, comparing aflibercept solution for injection 2 milligram (mg) monthly with laser photocoagulation in subjects with macular edema secondary to BRVO. At week 24, the primary endpoint of the study, 53% of patients who received aflibercept solution for injection 2 mg monthly gained at least 15 letters (equivalent to three lines) in best corrected visual acuity (BCVA) from baseline, compared to 27% of patients who received laser (p<0.001). In addition, aflibercept solution for injection met a key secondary endpoint, achieving a 17.0 letter mean improvement over baseline in BCVA compared to a 6.9 letter mean improvement in patients who received laser (p<0.0001).
Aflibercept solution for injection into the eye was generally well tolerated. Through week 24, the most common ocular adverse events in patients treated with aflibercept solution for injection were conjunctival hemorrhage and eye pain. The incidence of serious adverse events (SAE) was 9.9% in the aflibercept solution for injection group and 9.8% in the laser group. Up to week 24, one death and one Anti-Platelet Trialists' Collaboration (APTC) defined event (non-fatal stroke) occurred during the trial, both events occurred in patients in the laser group. There were no cases of intraocular inflammation. There was one ocular SAE in a patient in the aflibercept solution for injection group, which was a traumatic cataract.
About Retinal Vein Occlusion
Retinal Vein Occlusion (RVO) includes Branch Retinal Vein Occlusion (BRVO) and Central Retinal Vein Occlusion (CRVO). 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 responsible for seeing fine details. In CRVO, the blockage occurs in the main retinal vein at the optic nerve. In BRVO, the blockage occurs in one of the branches of the main retinal vein. If a blockage of 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, which describes swelling of the macula, which is the central portion of the retina.
About VEGF and 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 60 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 BRVO.
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.