A study of the safety, efficacy, and cost-effectiveness of using non-vitrectomised subretinal anti-VEGF injections to treat neovascular age-related macular degeneration

开始日期2024-12-01

申办/合作机构-

NCT06349044 / RecruitingN/AIIT

A Randomized, Multicenter Phase II Basket Study of Hypofractionated Radiotherapy/Stereotactic Body Radiotherapy Followed by Immunotherapy-Based Systemic Therapy +/- L. Rhamnosus M9 for the First-Line Treatment of Advanced Digestive System Malignancies

Based on the interaction between radiation therapy and immunotherapy and the potential potentiation of Probio-M9 for the treatment of ICIs, this study is planned to design an integrated treatment protocol for the first-line treatment of advanced gastrointestinal tumors through the use of macrofractionated radiotherapy as a means of immune activation, combined with the synergistic effect of Probio-M9 microbial agents and PD-1 inhibitors.

开始日期2024-03-20

申办/合作机构

浙江省肿瘤医院

NCT02321267 / Recruiting临床4期IIT

Cohort Study of the Clinical Course of Macular Diseases in Kagawa (Kagawa Macula Cohort Study)

Macular diseases often cases severe visual impairment. Recent clinical introduction of anti-vascular endothelial growth factor agents may change the clinical course of various macular diseases, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), central serous chorioretinopathy (CSC), myopic choroidal neovascularization (CNV), retinal vein occlusion (RVO), diabetic macular edema (DME), and so forth. The advance in vitrectomy improve visual outcomes in some maculae diseases, including epiretinal membrane (ERM), macular hole (MH), vitreomacular traction syndrome (VMTS).
Patients with such macular diseases are registered and are followed up for 5 years with appropriate treatment for each patient. By the analysis of the correlation between initial examinations and final visual acuity, factors associated with good visual prognosis will be elucidated.

开始日期2014-12-01

申办/合作机构

Kagawa University

100 项与哌加他尼钠相关的临床结果

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100 项与哌加他尼钠相关的转化医学

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100 项与哌加他尼钠相关的专利（医药）

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项与哌加他尼钠相关的文献（医药）

2024-08-01·Biochemical Genetics

A Comprehensive Analysis of NRP1 in Malignancies Provide Therapeutic Implication for Treating Cancer Patients Infected with SARS-CoV-2

Article

作者: Chen, Shuzhao ; Wang, Yun ; Song, Yiling ; Zhang, Limei ; Liang, Yang ; Xie, Kunying

COVID-19 (Coronavirus disease 2019) is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which can lead to pneumonia, cytokine storms, and lymphopenia. Patients with cancer are more susceptible to SARS-CoV-2 infection and severe COVID-19 due to immunosuppression. Recent studies have indicated that NRP1 (Neuropilin 1) may act as a novel mediator of SARS-CoV-2 entry into the host cell. As no systematic review has been performed investigating the characteristics of NRP1 in pan-carcinoma, we comprehensively analyzed NRP1 in patients with pan-cancer. Using a bioinformatics approach, we aimed to systematically examine NRP1 expression profiles in both pan-carcinoma and healthy tissues. We found that lung and genitourinary cancers have a relatively higher NRP-1 expression than other cancer patients, suggesting that these patients may be more susceptible to SARS-CoV-2. Our analysis further revealed that NRP1 expression was downregulated in Vero E6 cells, whole blood, lung organoids, testis tissue, and alveolospheres infected with SARS-CoV-2. Notably, NRP1 was associated with immune cell infiltration, immune checkpoint genes, and immune-related genes in most patients with cancer. These findings suggest that, in patients with specific types of cancer, especially lung and genitourinary, high expression of NRP1 contributes to greater susceptibility to SARS-CoV-2 infection and an increased risk of damage due to cytokine storms. Overall, NRP1 appears to play a critical role in regulating immunological properties and metabolism in many tumor types. Specific inhibitors of the NRP1 antigen (pegaptanib, EG00229, or MNRP1685A) combined with other anti-SARS-CoV-2 strategies may aid in treating patients with lung and genitourinary cancers following SARS-CoV-2 infection.

2024-04-16·Current Diabetes Reviews

Exploring the Therapeutic Potential of Anti-VEGF Drugs for the Management of Diabetic Retinopathy: An Overview

Article

作者: Gowthamarajan, K ; Ponnusankar, S ; Khandelwal, Aman ; Nirmal, Jayabalan

Abstract:The discovery of antivascular endothelial growth factor medications has resulted in a substantial change in diabetic retinopathy treatment. The most common cause of diabetic retinopathy blindness is Diabetic Macular Edema. The pathophysiology of Diabetic Macular Edema is thought to include the well-known pro-angiogenic and pro-permeability factor vascular endothelial growth factor. Over the past decade, drugs that impede the functions of vascular endothelial growth factors have established themselves as a standard-of-care treatment for a range of ocular ailments and improved patients' clinical results with diabetic retinopathy and Diabetic Macular Edema, and their frequency has grown exponentially with the introduction of these agents Pegaptanib, Ranibizumab, and Aflibercept which are approved for ophthalmic indications, while Bevacizumab is used off-label. These medications delivered intravitreally have halted the vascular development of diabetic retinopathy. Various randomized trials have proven that antivascular endothelial growth factor medication is safe and effective in preserving vision. Following an extensive period of preclinical development aimed at enhancing and defining its biological impacts, these drugs were shown in clinical trials to be effective in treating diabetic retinopathy and other ophthalmic conditions. Data from various sources suggest that Pegaptanib, Ranibizumab, and Aflibercept are costly, while Bevacizumab is cost-effective, and in low and middle-income nations, it is thus a desirable therapy choice. However, issues with compounding, counterfeiting, and off-label usage restrict its availability in many nations. The pharmacology, pharmacokinetics, pharmacodynamics, adverse effects, and contraindications of antivascular endothelial growth factor agents are discussed, and the results of clinical trials evaluating their efficacy are summarized.

2024-03-03·Expert Opinion on Drug Safety

A real-world disproportionality analysis of anti-VEGF drugs from the FDA Adverse Event Reporting System

Article

作者: Lu, Peiwen ; Zhou, Ruishan ; Chen, Junheng ; Cai, Yongming ; Han, Fangfang ; He, Mingxiu ; Shi, Yiyang

BACKGROUNDThe association between anti-vascular endothelial growth factor (VEGF) drugs and ocular adverse events (AEs) has been reported, but large real-world studies of their association with systemic AEs are still lacking.METHODSA disproportionality analysis of reports from the FDA Adverse Event Reporting System from January 2004 to September 2021 was conducted to detect the significant ADR signals with anti-VEGF drugs (including aflibercept, bevacizumab, brolucizumab, pegaptanib, and ranibizumab).RESULTSA total of 2980 reported cases with 7125 drug-AEs were included. Five drugs were all associated with eye disorders, and pegaptanib and ranibizumab were also associated with cardiac disorders. For ranibizumab, pegaptanib, bevacizumab and aflibercept, the proportions of cardiac AEs were 8.57%, 5.62%, 3.43% and 3.20%, respectively, and the proportions of central nervous AEs were 8.81%, 7.41, 5.86% and 5.68%, respectively. In multiple comparisons, ranibizumab was significantly higher than bevacizumab and aflibercept in the proportion of cardiac AEs (P < 0.001), and ranibizumab was significantly higher than aflibercept in central nervous AEs (P < 0.001).CONCLUSIONSOur findings support the associations between anti-VEGF drugs and ocular AEs, cardiac AEs, and central nervous AEs. After intravitreal injection, attention should not only be paid to ocular symptoms, but also to systemic symptoms.

项与哌加他尼钠相关的新闻（医药）

2024-10-29

·同写意

围攻眼科药王

此次医博会由同写意策划，以“发展新质生产力，共享健康新未来”为主题，用全新的视角瞄准国内外医药及大健康产业发展前沿。诚邀海内外医药及大健康各界嘉宾齐聚中国医药城，共赴时代之约。展位/报告火热征集中！近期，罗氏眼科双抗法瑞西单抗（Vabysmo）新适应症在华获批，用于治疗视网膜静脉阻塞继发黄斑水肿（MEfRVO）。眼科药王阿柏西普（Eylea）再受打击。自2015年销售额反超雷珠单抗（Lucentis）以来，阿柏西普一直统治着整个眼科抗VEGF药物市场，且常年霸榜全球畅销药物TOP10。但随着专利到期，在即将来临的大量生物类似药以及创新药的围剿下，阿柏西普岌岌可危。 1 钻石赛道开启视力障碍是一种改变生活的疾病，影响着全球约22亿人。据沙利文报告，2022年全球眼科药物市场规模已经达到372亿美元，预计2030年将达到734亿美元。2022年中国的规模达到43亿美元，预计2030年将达到169亿美元。图一：眼科药物市场规模来源：参考来源1 眼科药物市场增长迅猛，是非肿瘤领域的钻石赛道。而这一赛道内最亮眼的明星药物类别，自然属于诞生了眼科药王阿柏西普的抗VEGF药物（anti-VEGF，抗血管内皮生长因子）。 VEGF是一种促进血管内皮细胞增生的分子，VEGF家族包括VEGF-A、VEGF-B、VEGF-C、VEGF-D、VEGF-E和胎盘生长因子（PIGF），具有促进血管通透性增加、细胞外基质变性、血管内皮细胞迁移、增殖和血管形成等作用。研究发现VEGF的高表达与年龄相关性黄斑变性（AMD）、糖尿病视网膜疾病变（DR）等视网膜疾病密切有关，因此，VEGF成为了治疗眼科疾病的潜力靶点。历经多年开发，眼科抗VEGF药物目前已成为视网膜疾病的首要疗法，包括湿性年龄相关性黄斑变性（nAMD）、糖尿病性视网膜病变(DR)、糖尿病性黄斑水肿(DME)和视网膜静脉阻塞（RVO）以及早产儿视网膜病变（ROP）。其中，年龄相关性黄斑变性与糖尿病视网膜病变均位居引发视力障碍或失明的前五大原因。年龄相关性黄斑变性（AMD）是一种广泛分布的眼科疾病，主要影响老年人的视力，全球估计有1400万人受到影响。它是60≥岁个体中心视力丧失的主要原因之一。其中，湿性AMD也称为渗出性AMD或新生血管性AMD（nAMD），影响全球超过1500万人，约占70岁及以上人口的5%。而糖尿病视网膜病变（DR）是糖尿病的一种普遍的微血管并发症，影响大约30-40%的糖尿病患者，其中DME是DR的最普遍并发症之一。并且，近年来随着老年化加剧与糖尿病患病率的逐年上升，nAMD与DR、DME患病人数将持续上升。根据弗若斯特沙利文数据，仅中国2022年便分别有400万例nAMD、730万例DME患者，预计到2026年，患者人群数量将扩大至440万例nAMD和790万例DM，市场潜力巨大。随着商业化开发的深入，三种药物接力拉开了钻石赛道的帷幕。眼科抗VEGF药物的历史由哌加他尼（Macugen）在2004年首度开启，但在临床试验中，哌加他尼的临床数据虽优于安慰剂，大多数患者视力仍然呈下降趋势，现在临床已很少应用此药。图片2：眼科抗VEGF药物时间线参考来源：公开资料整理哌加他尼是先行者，但是眼科抗VEGF药物的第一次辉煌却由罗氏2006年上市的雷珠单抗所铸造。相较于哌加他尼的不温不火，雷珠单抗因疗效显著，在上市后很快名声大噪，首年便实现了7.1亿美元的销售额。上市首年《科学》杂志还将其评为年度十大科技成果之一，称其为“人类历史上第一次让AMD患者视力得到提高的疗法”。在2011年前，雷珠单抗可以说是独霸眼科抗VEGF药物市场，其巅峰销售额超过43亿美元。一直到再生元的当家花旦阿柏西普上市，眼科抗VEGF药物先锋雷珠单抗备受打击，进入了屈辱时代。阿柏西普的崛起可谓是抗VEGF眼科药物市场上的一场“突袭”。凭借着其最长可以三个月给药一次的优势，阿柏西普犹如一匹黑马，迅速在湿性老龄相关性黄斑变性（nAMD）治疗领域中站稳脚跟。它的推出不仅改变了治疗方式，还给竞争对手雷珠单抗带来了一场“市场地震”。图片3：阿柏西普与雷珠单抗销售额对比来源：参考来源2 在阿柏西普上市年后的第一年，它便差点突破10亿美元销售额大关，给当时市场占主导地位的雷珠单抗造成了强烈冲击。到2015年，阿柏西普不但成功反超了雷珠单抗，还登上了全球抗VEGF药物销售冠军的宝座，并自此一路高歌猛进，成为这个市场上无可争议的霸主，常年霸榜全球畅销药物TOP10。继眼科药王诞生，眼科药物这一钻石赛道终于真正的被阿柏西普完全开启。 2 前后围剿专利悬崖是重磅药物们避不开的梦魇。前任全球药王修美乐在巅峰时期（如2022年）的销售额达到了212.37亿美元，然而，到了2023年，其销售额骤降至144.04亿美元，同比下滑了32.2%。进入2024年，修美乐的颓势依旧未改，第一季度销售额仅为22.7亿美元，同比下降了35.89%，且全年销售额极大概率难以破百亿美元。罗氏的三驾马车贝伐珠单抗(Avastin)、利妥昔单抗(Rituxan)和曲妥珠单抗(Herceptin)，23年销售额合计不足45亿瑞士法郎，较巅峰时期缩量近80%。虽然从现有竞争格局来看，阿柏西普仍然具有极大的销售优势，但时间却不站在它这边。在生物类似药大举进攻之前，全新作用机制的双抗药物早已经发起奇袭。法瑞西单抗（Vabysmo）是一款双特异性抗体药物，开发用于治疗眼科疾病，特别是与视网膜血管异常相关的疾病。它由罗氏（Roche）旗下的基因泰克（Genentech）开发，主要针对两种靶点：血管内皮生长因子A（VEGF-A）和血管生成素-2（Ang-2）。法瑞西单抗的双重靶点机制使其不仅可以抑制VEGF-A的作用，还能够抑制Ang-2，后者也是血管生成和血管渗漏的关键调节因子。通过这种双重抑制，法瑞西单抗在减少病理性血管生成、改善血液循环和减缓炎症反应方面显示出了较强的潜力。法瑞西单抗已经在多个临床试验中取得了良好效果，并于2022年被美国食品和药物管理局（FDA）批准用于治疗nAMD和DME。与阿柏西普相比，法瑞西单抗将治疗周期延长到了每4个月一次，显著的减小了注射次数。由于优异的药效，法瑞西单抗的销售额一经上市便开始大幅放量（23年已达23.57亿瑞士法郎），并对阿柏西普的销售进行了冲击（阿柏西普2023年的全球销售额为92.15亿美元，同比下滑4%）。除了强力新竞品的冲击，生物类似药们更是已经蓄势待发。从全球市场来看，早在2021年10月，Mylan就向FDA递交了M710的上市申请，2021年12月获得了FDA的受理。随后，Formycon和Celltrion等公司接连向FDA发起了阿柏西普生物仿制药的申请。截至目前，已有五款阿柏西普的生物类似药获得FDA批准，最新批准的为安进在2024年8月获批上市的Pavblu。虽然再生元想法设法的通过专利诉讼进行阻止，如其在2024年1月对安进提起了侵权诉讼，指控Pavblu侵犯了阿柏西普32项专利，请求法院下令禁止安进上市销售Pavblu。但在2024年9月24日，美国西弗吉尼亚州地方法院驳回了“再生元阻止阿柏西普生物类似药Pavblu上市销售”的诉讼请求。裁决结果公布后，再生元股价应声下跌。从国内市场来看，2023年12月,齐鲁制药阿柏西普生物类似药获批上市，成为国产首款，将和12月在中国同时获批的法瑞西单抗共同携手打破国内市场此前雷珠单抗、阿柏西普、康柏西普的三足鼎立之势。此外，2024年7月16日,CDE网站显示,博安生物的阿柏西普眼内注射溶液申报上市。该品种是第2款申报上市的国产阿柏西普生物类似药。生物类似药的大幅入侵已成定局。除开已上市的入局者们，从研发端口来看，全球范围内至少有105个抗VEGF眼科药物项目在研（截至2023年10月）。其中，仅与最炙手可热的法瑞西单抗拥有共同靶点VEGF/ANG-2的双抗药物就已有至少8款在研。图片4：眼科双抗竞争格局来源：参考来源3 国内市场的研发更是如火如荼，目前处于三期临床阶段靶向 VEGF 眼科类似药就有5款，其中阿柏西普、雷珠单抗分别有3款、2款。图片5：国内眼科双抗竞争格局来源：参考来源3 创新药方面，目前国内至少有18款在研眼科抗VEGF创新药。全球市场与国内市场的众多竞争者们都已迫不及待入场分食眼科药王阿柏西普的市场。而在即将到来的创新药与生物类似药的全面围剿下，不知阿柏西普是否在那些前任药王的历史里早已经看到了自己惨痛的未来。 3 继承者们阿柏西普在其原研厂家再生元心里有着极为特殊的情感。作为再生元开发的第一个大药，是它将上市后便陷在财务困境中二十年的再生元拉出泥潭，也是它见证成再生元从一个初创企业成为了营收超百亿美元、市值超千亿美元的制药巨头（Eylea推出后，股价5年间翻了10倍）。图片6：再生元营收来源：参考来源4 尽管不舍，尽管提起了大量专利诉讼，尽管开发了高剂量HD，但也仅仅只能延缓阿柏西普的衰败之路，事物发展的客观大势无法阻挡. 但幸运的是，继承者们已至。就如同打造了前任药王修美乐的艾伯维，修美乐重挫后，其还有瑞莎珠单抗（SKYRIZI）和乌帕替尼（Rinvoq）来接棒。2023年，Skyrizi的销售额为77亿美元，同比增长50%，Rinvoq销售额为39亿美元，同比增长57%。两者销售额共计超过100亿美元，到2027年将超过修美乐达到270亿美元的峰值收入。就如同打造了三架马车的罗氏，老三架马车失速后，新三架马车帕妥珠单抗（Perjeta）、恩美曲妥珠单抗（Kadcyla）、阿替利珠单抗（Tecentriq）也早已扬帆起航，在2021年反超了销售额下滑的老三架马车。再生元也有阿柏西普的继承者，即度普利尤单抗（Dupixent）。作为全球首个获批上市的IL-4Rα靶向单抗，度普利尤单抗市场表现非常亮眼，2023年销售已突破百亿美元(115.89亿美元)，跻身2023全球畅销药TOP6，且在24年上半年销售额已经超越阿达木单抗，荣升全球自免药王。对于再生元来说，度普利尤单抗在阿柏西普失势之后还会陪着他走很远的路，也能够在很长的时间里提供再生元所需的资金与前进动力，再生元可以放手去打造更多的重磅药物。图片7：再生元临床项目来源：参考来源4 截止2024年8月报告，目前再生元拥有包括肿瘤、自免、眼科等重磅领域在内至少35个临床在研药物，其中10个已经进入了临床三期，增长动力十足，相信后续其会持续给到我们惊喜。最后，对于一家药企而言，纪念优秀前任最有力的方式，也许就是开发出一款又一款畅销的重磅药物。参考文献： 1、前浪后浪“争斗”不休，VEGF眼药市场谁主沉浮？，药智头条 2、《中国药品制剂行业发展态势分析与投资战略评估报告（2022-2029年）》，观研天下 3、申万宏源、西南证券研究 4、各公司官网 5、Ophthalmic Use of Targeted Biologics in the Management of Intraocular Diseases: Current and Emerging Therapies. https://doi.org/10.3390/antib13040086 同写意媒体矩阵，欢迎关注↓↓↓

专利到期

2024-09-04

·GlobeNewswire-Health Care

iSTAR Medical continues to strengthen US presence with appointment of Chief Medical Officer and Vice President of Clinical Affairs

For immediate release iSTAR Medical continues to strengthen US presence with appointment of Chief Medical Officer and Vice President of Clinical Affairs WAVRE, Belgium — 4 September 2024: iSTAR Medical, a medtech company delivering breakthrough eye care solutions to patients, today announces the strengthening of its leadership team with the appointment of Richard (Rick) Beckman, M.D., as Chief Medical Officer and member of the Board, and Kristine (Kris) Curtiss as Vice President of Clinical Affairs. Rick’s duties as Chief Medical Officer (CMO) will cross clinical, regulatory, and medical affairs. Additionally, he will be a member of the Board. Rick brings deep insight and experience from his previous roles as a CMO, most recently at Adverum, and has an extensive background in the medical and surgical management of glaucoma as well as in glaucoma pharmaceutical and device development. Based in the US, he will be critical to the successful development of the Company’s clinical programs and will report to the Chief Executive Officer (CEO), Michel Vanbrabant. Kaweh Mansouri, M.D., who is stepping down as CMO to focus on his appointment as Executive Vice President of the World Glaucoma Association, will continue as a consultant to the Company as a Senior Medical Advisor. Kris joins the leadership team as Vice President (VP) of Clinical Affairs with over 20 years of clinical research experience and having held senior positions in biotech, medical device, and large pharma companies. She will lead iSTAR Medical’s clinical organization including its STAR-V trial and will report to the CMO, Rick Beckman. David Stocker, who held the role of VP of Clinical Affairs will return to his previous responsibilities in the commercial organization as VP Sales, Marketing, and Training. Michel Vanbrabant, CEO of iSTAR Medical, commented: “We are delighted to welcome Rick and Kris to our leadership team. Their combined global experience in clinical, regulatory, and medical affairs will be instrumental in guiding the Company towards delivering breakthrough eye care solutions to a greater number of patients in additional global territories. “I want to extend my gratitude to Kaweh for his significant contributions to iSTAR Medical thus far, which has helped us establish a global reputation for MINIject® as a safe and effective treatment option for glaucoma patients. We congratulate him and wish him the best of luck with his role as Executive Vice President of the World Glaucoma Association.” Richard Beckman, M.D., Chief Medical Officer and member of the BoardRick, a board-certified ophthalmologist and fellowship trained glaucoma specialist, is a seasoned professional with extensive experience in the healthcare and biotechnology sectors. He was previously CMO at Adverum Biotechnologies, ReNeuron, as well as Clearside Biomedical. He was formerly the head of the glaucoma therapeutic area at Alcon. Rick is currently the principal at RLB, M.D., Consulting and serves on the Board of OceanZero US. He holds an M.D. from University of Michigan, completing his ophthalmology residency at Henry Ford Hospital, after which he completed a glaucoma fellowship at Massachusetts Eye and Ear Infirmary/Harvard Medical School. Kristine Curtiss, Vice President of Clinical AffairsKris joins the iSTAR Medical team with extensive experience in clinical research and ophthalmology. She was previously VP Clinical Operations at Iveric Bio, Inc., and prior to that she held leadership positions at ophthalmic start-ups including PanOptica, Oraya Therapeutics, and OPKO. During her career, Kris has been a major contributor to 5 successful marketing applications, including Iverzay™ for Geographic Atrophy and Macugen® for exudative Age-related Macular Degeneration. She holds a Bachelor of Science in Chemistry from the University of Delaware and a graduate certificate in Project Management from Rutgers University School of Business. – Ends – For more information Paul van HagenChief Financial Officer, iSTAR Medicalnews@istar-medical.com For mediaICR ConsiliumAmber Fennell, Chris Welsh, Kris LamiSTAR@consilium-comms.com About iSTAR Medical iSTAR Medical is committed to delivering breakthrough eye care solutions. Our most advanced product, MINIject®, is approved in Europe for the treatment of open-angle glaucoma – the leading cause of irreversible blindness – and we are aiming to seek market approval in the US. We believe MINIject®’s distinctive tissue-integrating capabilities unlock a safer, and more effective option for patients. We are building an exceptional team and pipeline of potentially leading products such as MINIject® to establish new treatment paradigms in eye care conditions with the highest patient needs. iSTAR Medical is an independent company which entered a strategic partnership with AbbVie (NYSE: ABBV) in July 2022. The collaboration further supports the role of MINIject® in the treatment of glaucoma and accelerates iSTAR Medical’s goal to bring MINIject® to more patients globally while providing AbbVie the opportunity to further expand its diverse eye care portfolio. About MINIject® MINIject® is iSTAR Medical’s innovative MIGS device for patients with primary open-angle glaucoma. MINIject® combines the distinctive porous structure of its proprietary STAR material with the power offered by the supraciliary space. As a result, it is designed to enhance natural fluid outflow, reducing intraocular pressure (IOP) and the need for medication, while bio-integrating with surrounding tissue, limiting inflammation, fibrosis and subsequent complications. About GlaucomaGlaucoma is a progressive disease affecting over 100 million people globally, of which primary open-angle glaucoma is the most common form.1,2 IOP reduction, through medication or surgery, helps delay disease progression.3 Medication is generally the first line treatment, but the progressive addition of multiple drops can burden patients with side effects, compliance challenges and costs.2,3 Invasive surgery can present risks with irreversible complications and often requires long-term patient management.2,3 MIGS is the most promising and fastest-growing glaucoma therapy due to its enhanced safety profile.2 MINIject® is potentially best-in-class for its promising long-term efficacy and safety. 1 Jonas JB, Aung T, Bourne RR et al. "Glaucoma". Lancet 2017; 390: 2083–932 Market Scope, “2023 Glaucoma Surgical Device Market Report”, July 2023. 3 “European Glaucoma Society Terminology and Guidelines for Glaucoma”, 4th Edition: British Journal of Ophthalmology. 2017;101:1-195 https://bjo.bmj.com/content/101/5/73

高管变更

2024-07-04

·医药魔方

眼科黄金赛道，市场潜力持续爆发

近期，默沙东与眼科生物技术公司EyeBio达成最终收购协议，通过子公司以高达30亿美元的价格收购后者，其中包括13亿美元预付现金和17亿美元的潜在开发、监管和商业里程碑付款。默沙东曾在2013年将美国眼科业务剥离给Akorn Pharmaceuticals，2014年又以6亿美元的价格将眼科药物的部分权益出售给日本的参天制药。此次收购EyeBio意味着默沙东在阔别眼科市场10年后又重新回到这一阵地。事实上，当大量玩家在肿瘤免疫领域“卷出天际”时，以眼科赛道为代表的非肿瘤领域市场机会正在被更多企业挖掘下注。2023年12月，强生从MeiraGTx购得一款治疗x连锁色素性视网膜炎（XLRP）的基因疗法botaretigene sparparvovec，交易总金额高达4.15亿美元；2023年11月，艾伯维与Aldeyra达成协议，以4.01亿美元的总交易额获得干眼病新药Reproxalap的独家权益；2023年4月，安斯泰来斥资59亿美元收购Iveric Bio，获得一款地图样萎缩新药avacincaptad pegol；2022年底，安进收购Horizon，获得了该公司一款甲状腺相关眼病新药Tepezza…… 巨头此时纷纷入局的考虑在于眼科药物开发本就不是小众赛道，当下的市场规模和格局随着创新技术的涌现相比之前也有翻天巨变。眼底血管病变一度培育出了数款重磅炸弹级别药物，而今更多眼科疾病的临床需求被进一步挖掘和满足，正在孕育更多爆发的细分市场。眼底血管病变：VEGF靶向疗法持续迭代正常眼部血管结构及功能的维持依赖于血管生成促进因子和抑制因子的平衡状态。当此种平衡被打破时，新生血管形成的阀门即可开启，诱发多种眼底血管病变，包括：老年黄斑病变（AMD）、继发于病理性近视（PM）的脉络膜新生血管、糖尿病黄斑水肿（DME）、视网膜静脉阻塞（RVO）等。多种眼部新生血管过程涉及各类受体介导的细胞信号通路，其中刺激血管生成作用最强的是血管内皮生长因子（VEGF）。 VEGF是1989年Ferrara等从牛垂体滤泡星状细胞体外培养液中首先提纯出来的，根据其具有促血管内皮细胞有丝分裂的作用而命名。这一靶点起初被证明是肿瘤血管生成的介质，基于这一发现首款VEGF单抗贝伐珠单抗于2004年获FDA批准治疗转移性结直肠癌。不过，在几种视网膜缺血动物模型中，研究人员发现VEGF mRNA的表达与新生血管的形成具有空间和时间相关性。这与VEGF-A基因表达在缺氧时通过HIF依赖性转录激活而上调的观点一致。1994年，首次报道了继发于糖尿病和其他疾病的增殖性视网膜病变患者的眼水体和玻璃体中VEGF水平升高。随后，多种VEGF抑制剂的动物研究直接证明了VEGF在缺血诱导的眼内新生血管中的介质作用。 Eyetech/辉瑞联合开发的人工合成寡核苷酸序列培加他尼（pegaptanib）对VEGF165异构体具有高亲和力，于2004年12月获美国FDA批准上市，用于治疗AMD。由于其只能结合完整的VEGF165，而不会与其他VEGF异构体或仍有生物活性的VEGF165裂解片段结合，因此，随着后续雷珠单抗的问世，培加他尼逐渐淡出市场。贝伐珠单抗由基因泰克（罗氏旗下）研发，是第一个人源化抗VEGF的IgG单克隆抗体，其也曾被尝试开发用于治疗AMD。不过，科学家发现，由于内外丛状层对大分子扩散的阻力作用，相较于分子量较大的全长IgG抗体，小抗体片段（如单链可变片段和Fabs）比IgG抗体具有更好的组织穿透性。并且，随后人们了解到，静脉注射贝伐单抗联合细胞毒性化疗对癌症患者的动脉血栓栓塞事件发生率比单独化疗增加了两倍，年龄大于60岁和有血栓栓塞史是危险因素。基于此，基因泰克的科学家在贝伐珠单抗的基础上设计出了第二代抗VEGF单克隆抗体Lucentis（雷珠单抗）。Lucentis是仅有Fab段的抗体，没有Fc段，分子量更小，具有更短的半衰期，并且不会引发免疫系统的激活，这使得它成为治疗眼睛疾病的理想选择。贝伐珠单抗和雷珠单抗的构建步骤此外，由于Lucentis能结合所有检测到的VEGF异构体及其降解产物，因此展现出很好的治疗效果，自2006年6月获批以来，先后在全球多国斩获多项眼底疾病适应症，包括AMD、DME等。诺华早在2003年便与基因泰克达成合作，获得在北美以外地区开发和销售Lucentis的独家许可，用于治疗眼部疾病相关的适应症。巨大的全球市场使诺华在这款药物上收获不菲。即使过专利期的当下，2023年Lucentis全球销售额仍高达19.72亿美元，诺华占据大头（14.75亿美元）。目前，全球已上市的雷珠单抗生物类似药多达8款，Lucentis持续面临着生物类似药和其他竞品的冲击。来源：医药魔方NextPharma 为此，罗氏于2021年推出了雷珠单抗眼内港式给药系统Susvimo，这是第一个实现生物制品缓释的眼用植入剂，每年只需注射两次。罗氏期望以此来延长该药物的生命周期，不过其目前的销售表现平平。继雷珠单抗之后横空出世的Eylea (阿柏西普) 是一种可溶性受体融合蛋白，是由人VEGFR胞外结构域与人IgG1的Fc结构域融合后形成的同源二聚体糖蛋白。其能阻断VEGF-A的所有亚型，结合VEGF的亲和力是雷珠单抗的100倍，并且具有结合VEGF和PGF的双重作用。阿柏西普再次变革了眼底疾病的治疗，凭借优异的治疗效果，已成为nAMD等眼底疾病标准治疗药物。阿柏西普最初由再生元公司研发，起初聚焦于癌症治疗。其眼科权益经赛诺菲转手后被拜耳接盘，后者获得阿柏西普美国外眼病权益。该药物于2011年获得FDA批准治疗眼科疾病，且仅用一年的时间就占据了美国黄斑变性治疗领域22%的市场份额，上市第一年的销售额为8.4亿美元，第二年便成为重磅炸弹药物，迄今仍然是再生元产品中主要来源，贡献了该公司2/3以上产品收入。来源：医药魔方NextPharma Eylea同样面临专利悬崖的挑战，其核心专利也将陆续到期，来自Biocon（Yesafili）、Samsung Bioepis/渤健（Opuviz）等公司的生物类似药均会成为其强力竞争对手。为此，拜耳和再生元开发了阿柏西普高剂量版本（8mg)，可将治疗间隔从每2个月延长至每4个月一次。该药物已在欧美日等国获批上市，今年第一季度，Eylea HD在美国营收2亿美元。再生元认为，Eylea HD有潜力成为下一代抗VEGF治疗的标准疗法。值得一提的是，该产品在中国也已进入申报上市阶段。伴随着市场潜力的释放，抗VEGF治疗逐渐进入长效治疗时代，诺华开发的Beovu（brolucizumab）是一种人源化单链抗体片段（scfv），仅保留两个可变区，比雷珠单抗更小，并具有很高的亲和力，可以实现更高摩尔剂量给药，是首个只需要每3个月注射1次的抗VEGF疗法。凭借在眼科领域深耕数十年的基底，罗氏2022年新推出VEGF-A/ANG-2眼科双抗Vabysmo（法瑞西单抗）再次延长患者用药间隔。针对nAMD患者的一年研究（TENAYA和LUCERNE），和糖尿病黄斑水肿（DME）患者的两年研究（YOSEMITE和RHINE）结果表明，与每2个月一次的阿柏西普相比，法瑞西单抗组的患者在视力改善和视网膜解剖学获益方面取得了相似的效果。所有4项研究的两年后数据均表明，超过60%的法瑞西单抗组患者能够将治疗周期延长到每4个月一次，同时还能改善和保持视力。此外，在两年内，接受法瑞西单抗治疗的nAMD和DME患者的中位注射次数分别比阿柏西普组少33%和21%。 Vabysmo的销售表现可谓如日中天，上市首年销售超6亿美元，上市以来累计销售额高达42亿美元。也是罗氏目前市场增长表现最好的药物之一，2024Q1同比增长108%。抗VEGF药物间的市场争夺战还在继续，这类药物不仅改写了眼底病的治疗史，为患者带来了福祉，同时也吸引了更多玩家进入眼科赛道。更多眼科疾病市场潜力待释放除了上文提到的眼底疾病外，干眼症、白内障、青光眼等常见眼科疾病以及一些较罕见的眼科疾病，比如甲状腺相关眼病、地图样萎缩等也存在巨大临床未满足需求。近些年越来越多公司的相关产品逐渐获批上市或走向临床后期，有望为患者提供更多新的、可用的治疗方法。干眼症（DED）是由多种原因导致的眼表损伤，患者不仅要忍受诸如干燥感、异物感、疼痛或瘙痒等不适症状，还会因为泪膜不稳定导致视觉障碍。其抗炎治疗常用药物主要为环孢素。其中艾尔建（现为艾伯维旗下）是最早开发环孢素滴眼液的企业，其Restasis的销售峰值曾在2021年达到12.9亿美元。然而，已上市的DED药物只可缓解眼干、视疲劳及视力模糊不适症状，很难达到治愈的目的，目前DED仍缺乏有效治疗手段。不过，近几年干眼症领域频传积极进展。 2016年，Xiidra（立他司特）获批上市，是FDA批准的首款用于治疗眼损伤迹象和患者症状的干眼病疗法，年销售额曾超4亿美元； 2018年，Sun Pharma的Cequa (环孢素)获FDA批准上市，是首个获FDA批准的采用NCELL技术的环孢素治疗药物，康哲药业拥有在大中华区的权益； 2020年，FDA批准0.25% Eysuvis（依碳酸氯替泼诺）用于短期（最多两周）治疗干眼症，是首个专门针对干眼病短期治疗的处方疗法。2022年，其权益被爱尔康收购； 2021年，Oyster Point的Tyrvaya（伐尼克兰鼻喷剂）获FDA批准治疗干眼症的症状和体征，是首个也是唯一一个获批治疗干眼症的鼻喷剂，箕星药业拥有大中华区开发权益； 2023年，Novaliq公司全氟己基辛烷滴眼液（此前称NOV03）获FDA批准上市，用于治疗干眼症的体征和症状。恒瑞医药拥有该药在中国的独家权利，并已经在中国递交上市申请。除此之外，Aldeyra开发的first in class小分子反应性醛类物质（RASP）抑制剂Reproxalap也进入后期开发阶段。今年6月，Aldeyra宣布已完成治疗干眼症III期试验的受试者入组，并计划于今年下半年重新递交NDA。此外，Reproxalap用于治疗过敏性结膜炎的III期试验基于积极的结果，有望递交NDA。艾伯维在眼科领域布局有干眼病药物Restasis以及青光眼的药物Lumigan (贝美前列素)/Ganfort (贝美素噻吗洛尔)和Alphagan/Combigan (溴莫尼定)。为了补充眼科管线，其于去年11月与Aldeyra达成协议，以4.01亿美元的总交易额获得Reproxalap在美国的共同开发、生产和商业化权益以及美国以外的独家权益。 Aldeyra在研管线还包括用于治疗视网膜色素变性症的候选药物ADX-2191以及治疗干性年龄相关性黄斑变性/地理萎缩的候选药物ADX-631。甲状腺相关眼病（TED）是一种常发生于甲亢患者身上的自身免疫性疾病，临床通常表现为眼球突出、复视、视力模糊和面部畸形等。该疾病主要是由于患者自身抗体激活了眼框内胰岛素样生长因子1受体（IGF-1R）所导致。 2020年，FDA批准了首款治疗TED的药物Tepezza（teprotumumab），Tepezza上市第一年就带来销售8.2亿美元的惊艳表现，2021年收入更是同比增长103%达到16.61亿美元，迅速跻身“重磅药物”行列。Refinitiv分析曾预测2028年这款产品销售额将达到38.5亿美元。2022年12月，安进以278亿美元全现金方式收购Horizon Therapeutics获得了这款药物的开发权益。地图样萎缩（GA）是AMD的一种晚期病变，会导致不可逆转的失明。全球约有500万人患有GA。近两年这一疾病也相继获批了两款新药，2023年，Apellis公司的补体C3疗法Syfovre（Pegcetacoplan）的玻璃体内注射剂型和Iveric Bio公司的补体C5疗法Izervay（avacincaptad pegol）相继获得FDA批准治疗GA；在Izervay获批前3个月，安斯泰来便与Iveric Bio达成最终协议，通过美国控股子公司Berry Merger Sub以每股40美元现金收购后者100%的流通股，总股本价值约59亿美元。由此可见，眼科领域依然有很多的临床需求待进一步挖掘。多款干眼病新药的权益被争相售出，Reproxalap被艾伯维看上，安进重金收购Horizon，安斯泰来收购Iveric Bio，足以说明这些眼科类药物依然被很多制药企业看好，有着光明的前景。总结随着人口老龄化、电子产品的广泛使用，各类眼部疾病发病率上升，弗若斯特沙利文预测，到2025年全球眼科药物市场规模将达到464亿美元，2030年将达到739亿美元。抗VEGFR在眼底疾病治疗中的突出表现打开了百亿级眼科市场，而随着未来更多眼科疾病新药被开发出来，这一市场空间仍有巨大的释放潜能。 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

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KEGG	Wiki	ATC	Drug Bank
D05386	哌加他尼钠	S01LA03	DB04895

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
黄斑变性	菲律宾	Pfizer Inc.	2006-05-23

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肿胀	临床3期	捷克	Pfizer Inc.	2005-09-01
肿胀	临床3期	意大利	Pfizer Inc.	2005-09-01
肿胀	临床3期	德国	Pfizer Inc.	2005-09-01
肿胀	临床3期	奥地利	Pfizer Inc.	2005-09-01
肿胀	临床3期	荷兰	Pfizer Inc.	2005-09-01
肿胀	临床3期	法国	Pfizer Inc.	2005-09-01
肿胀	临床2期	巴西	Pfizer Inc.	2005-09-01
湿性年龄相关性黄斑变性	临床2期	美国	Bausch & Lomb, Inc.	2004-09-17

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01573572 (CTgov)	临床4期	糖尿病性黄斑水肿 \| 年龄相关性黄斑变性 \| 视网膜静脉阻塞	131	pegaptanib sodium injection	衊鏇積憲選觸構範艱壓(製築夢襯範鹹遞窪襯遞) = 顧顧鹽蓋構艱廠壓築餘壓蓋積鬱齋範蓋蓋壓膚 (壓願淵齋襯鬱衊鹽積膚, 範醖鹹窪選襯壓鏇選鑰 ~ 顧醖積夢願網艱鬱鏇餘) 更多	-	2020-10-14
NCT00790803 (CTgov)	N/A	葡萄膜炎 \| 黄斑水肿	5	Pegaptanib (Macugen)	廠憲壓窪憲構淵膚構製(鑰範觸鏇淵範鏇遞襯鏇) = 築窪製簾糧蓋願蓋鏇繭夢構齋繭鏇築醖壓膚獵 (遞蓋襯壓憲顧顧餘選餘, 夢觸壓廠網積憲鑰齋鬱 ~ 選糧遞衊觸壓鑰襯襯醖) 更多	-	2013-09-26
NCT01100307 (CTgov)	临床3期	糖尿病性黄斑水肿 \| 黄斑水肿	243	pegaptanib sodium	構積網夢鬱醖鬱衊廠構(繭艱範襯壓衊顧淵遞膚) = 範夢糧壓鏇齋膚鹽醖糧鹽製醖鹹積鑰簾獵獵製 (窪觸遞製築襯淵廠衊襯, 簾壓窪餘夢鏇獵網鹹窪 ~ 餘夢窪蓋構艱製鹽憲艱) 更多	-	2013-07-15
ARVO2013	N/A	糖尿病性黄斑水肿 ischemia	30	Pegaptanib	齋艱願糧鏇範選願憲願(範獵鹽醖繭衊淵範夢壓) = 遞鹽顧鬱願壓壓網繭憲繭構壓醖糧膚觸積艱鏇 (衊觸憲夢醖築糧鏇襯窪 ) 更多	不佳	2013-06-01
ARVO2013	N/A	-	30	Pegaptanib	(糧遞網構襯構襯醖壓鏇) = 衊廠鹽衊觸鬱壓繭繭繭遞範膚壓窪壓齋艱鏇簾 (壓壓齋齋鑰範顧餘窪顧 ) 更多	不佳	2013-06-01
phase II study (ARVO2013)	临床2期	伴有糖尿病的增殖性视网膜病变	-	Pegaptanib+Progressive PRP	衊鑰鏇壓顧醖鹽壓淵選(製製鹹範顧鑰膚淵鏇遞) = 夢襯憲願蓋鏇積襯淵繭積淵艱鬱鏇選築鑰壓鑰 (壓繭鏇鏇淵鹽網膚膚糧 )	积极	2013-06-01
phase II study (ARVO2013)	临床2期	伴有糖尿病的增殖性视网膜病变	-	Pegaptanib	衊鑰鏇壓顧醖鹽壓淵選(製製鹹範顧鑰膚淵鏇遞) = 窪繭憲繭鑰構鬱夢觸積積淵艱鬱鏇選築鑰壓鑰 (壓繭鏇鏇淵鹽網膚膚糧 )	积极	2013-06-01
ARVO2013	N/A	伴有糖尿病的增殖性视网膜病变	20	Pegaptanib	(壓鬱窪範築鑰願鏇製壓) = 齋顧憲廠醖繭壓淵憲膚憲鹹壓廠齋製範鑰範構 (選範憲繭鏇壓觸選糧鏇 )	积极	2013-06-01
NCT01175070 (ARVO2012)	临床4期	糖尿病性黄斑水肿	-	Intravitreal Pegaptanib	網窪淵襯顧繭艱築艱遞(範膚衊積鏇遞齋窪構醖) = 築獵遞簾簾廠衊餘鏇廠簾壓襯淵衊糧窪繭簾夢 (獵蓋糧觸鹹鹹簾構鏇鹽, 0.93) 更多	-	2012-03-01
NCT01175070 (ARVO2012)	临床4期	糖尿病性黄斑水肿	-	Intravitreal Pegaptanib	網窪淵襯顧繭艱築艱遞(範膚衊積鏇遞齋窪構醖) = 鑰壓餘壓夢構壓壓襯顧簾壓襯淵衊糧窪繭簾夢 (獵蓋糧觸鹹鹹簾構鏇鹽, 1.70) 更多	-	2012-03-01
NCT01175070 (ARVO2012)	临床4期	糖尿病性黄斑水肿	16	Intravitreal Pegaptanib sodium 0.3 mg	(鬱廠鏇築衊齋憲壓糧繭) = 鹽築衊淵範鏇顧鑰夢窪選齋鏇蓋艱簾蓋餘鑰選 (鬱鏇觸窪顧艱鑰願淵窪, 414 ~ 518) 更多	-	2012-03-01
RIH 1006 (ARVO2012)	N/A	视网膜水肿 vascular endothelial growth factor (VEGF)	4	Intravitreal pegaptanib sodium 0.3 mg every 2 weeks for 3 doses, every 3 weeks for 2 doses, and then every 4 weeks for 3 doses	(憲鏇構鹹繭構遞淵獵構) = 觸鑰構鏇憲選鬱蓋願網顧選觸選壓選鹽選遞觸 (簾鬱遞顧築醖願壓淵範 )	-	2012-03-01