诺华眼科新药RTH258 II期临床疗效媲美拜耳Eylea

眼科护理的全球领导者——诺华旗下眼科单元爱尔康（Alcon）近日在美国亚利桑那州斯科茨代尔举行的第38届黄斑学会会议（Annual Macula Society Meeting）上公布了老年黄斑变性（AMD）新药RTH258第二个II期临床研究的数据。数据显示，改善视力方面，RTH258疗效及安全性媲美Eylea；同时，相比Eylea，RTH258具有降低给药频率并减少治疗负担的潜力。根据这些喜人数据，诺华已启动RTH258的III期项目。

该II期研究是一项前瞻性随机双盲多中心双组研究，在90例新生血管性（湿性）年龄相关性黄斑变性（wet-AMD）患者中开展，调查了RTH258相对于拜耳市售眼科药物Eylea（aflibercept,阿柏西普注射液）的疗效和安全性。主要目的是比较RTH258（6mg剂量）和Eylea（2mg剂量）在主要终点（即最佳矫正视力（BCVA）从基线至12周的平均变化）的疗效。数据显示，在视力增益方面，RTH258达到了相对于Eylea的非劣效性；RTH258治疗组异常视网膜积液减少数值更大并得到迅速改善；接受RTH258每3个月给药一次的患者，也经历了长期的治疗疗效；安全性方面，RTH258和Eylea的耐受性均良好，研究中未出现新的安全信号。

爱尔康高级副总裁Sabri Markabi表示，该研究证明了RTH258提高视觉结果的疗效，同时也表现出了降低给药频率并减少治疗负担的潜力。目前，爱尔康已启动III期项目，在湿性AMD群体中进一步调查RTH258相对于Eylea的疗效。首个III期研究将比较RTH258（3mg剂量及6mg剂量）与Eylea（2mg剂量）在主要终点即最佳矫正视力（BCVA）从基线至48周的平均变化。第二个III期研究也将在2015年内启动。这些研究中，患者将每3月给药RTH258一次，对于那些因病情活动被认为不适合3月给药方案的患者将给予2月给药方案；Eylea治疗组将根据其药物标签给药。

当前，眼科治疗领域，拜耳眼科药物Eylea正与罗氏和诺科药物Lucentis展开激烈竞争，2者均已获批用于新生血管性（湿性）年龄相关性黄斑变性（wet-AMD）的治疗。RTH258（原名ESBA1008）则是诺华旗下爱尔康研发的一种新型单链抗体片段，治疗上有望降低给药频率并减少治疗负担。老年黄斑变性（AMD）是导致50岁以上老年群体严重视力丧失的主要病因。据估计，全球约有2500-3000万AMD患者，该病使患者视网膜中心（即黄斑）劣化，导致中央视力逐渐丧失。

英文原文：Positive phase II data highlights benefits of Alcon's RTH258 for patients with neovascular (wet) age-related macular degeneration

-Phase II study met primary endpoint, demonstrating promising visual acuity gains in patients with neovascular (wet) age-related macular degeneration

-Data shows the potential for less frequent dosing and reduced treatment burden with RTH258 compared to aflibercept

-Phase III clinical trial program initiated in December 2014, with 1700 patients expected to be enrolled in more than 50 countries

Basel, February 27, 2015 - Alcon, the global leader in eye care, presented positive results from its second Phase II clinical study of RTH258 during the 38th Annual Macula Society Meeting in Scottsdale, Arizona. This study evaluated the efficacy and safety of the compound versus aflibercept in patients with neovascular (wet) age-related macular degeneration (AMD). RTH258 (formerly known as ESBA1008) is a novel, single-chain antibody fragment developed to treat wet AMD.

The Phase II study met its primary endpoint, demonstrating promising visual acuity gains that were non-inferior to aflibercept, with numerically greater reduction and rapid improvement in abnormal retinal fluid observed in RTH258-treated patients. Patients treated every three months with RTH258 also experienced a prolonged duration-of-action, potentially leading to a reduced treatment burden. A total of 90 patients diagnosed with wet AMD participated in the prospective, randomized, double-masked multicenter, two-arm study. The primary objective was to compare the efficacy of RTH258 6mg versus aflibercept 2mg with the primary endpoint being the mean change in best corrected visual acuity (BCVA), from Baseline to Week 12. Secondary endpoints included the change assessment in BCVA and central subfield foveal thickness (CSFT) as measured by spectral domain optical coherence tomography (SD-OCT). Both RTH258 and aflibercept were well tolerated and no new safety signal was reported during the study.

"Alcon is deeply committed to addressing unmet patient needs in retina, and RTH258 demonstrates the potential to improve visual outcomes and reduce the treatment burden for patients with wet AMD," said Sabri Markabi, Senior Vice President, Research & Development for Alcon. "We have initiated our Phase III study program based on the encouraging results we received from the Phase II studies with RTH258."

RTH258 Phase III Study Program Initiated
With these positive Phase II results, Alcon has initiated its Phase III clinical study program to evaluate the efficacy and safety of RTH258 versus aflibercept in patients with wet AMD. As part this innovative study program, Alcon expects to enroll approximately 1,700 patients in more than 50 countries worldwide. The primary objective of the first Phase III study is to compare the efficacy of RTH258 3mg and 6mg versus aflibercept 2mg, with the mean change in BCVA, from Baseline to Week 48 as the primary endpoint. The second study within the Phase III trial program will also compare the efficacy of RTH258 versus aflibercept, and is expected to commence in 2015. Patients participating in the Phase III studies will be dosed every three months with RTH258, while a bi-monthly-dosing regimen will be followed for those patients considered unsuitable for a quarterly dosing schedule due to disease activity. Aflibercept will be dosed according to its approved label. Please visit www.clinicaltrials.gov for further details about the RTH258 Phase III clinical trial program.

AMD is a leading cause of severe vision loss in people over age 50,[1],[2] and the United Nations estimates that it impacts 25 to 30 million people worldwide.[3] AMD occurs when the center of the retina, known as the macula, deteriorates leading to gradual loss in central vision.