预约演示
更新于：2025-02-15
Brolucizumab-dbll
溴珠单抗
更新于：2025-02-15
概要
基本信息
非在研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (2019-10-07), |
最高研发阶段(中国)申请上市 |
特殊审评优先审评 (美国) |
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结构/序列
Sequence Code 19665277
来源: *****
关联
65
项与 溴珠单抗 相关的临床试验NCT06498050
Brolucizumab Efficacy and Safety Single-Arm Descriptive Trial in Patients With Persistent Diabetic Macular Edema
The goal of this clinical trial is to evaluate the efficacy of brolucizumab 6 mg in Chinese patients with persistent diabetic macular edema (DME). It will also learn about the safety of brolucizumab 6 mg.
The main questions it aims to answer are:
Does brolucizumab 6 mg reduce central subfield thickness (CST) and improve best-corrected visual acuity (BCVA) of participants? What medical problems do participants have after receiving intravitreal injections of brolucizumab 6 mg? Researchers will compare baseline CST and BCVA to those at each post-baseline visit to see if brolucizumab 6 mg works to treat persistent DME.
Participants will:
Receive brolucizumab 6 mg via intravitreal injections following two treatment patterns:
Treatment Pattern 1: every 6 weeks for 5 injections Treatment Pattern 2: every 6 weeks for 3 injections followed by 1 injection after 12 weeks Visit the clinic 8 times for treatment and assessments over the course of 28 weeks
The main questions it aims to answer are:
Does brolucizumab 6 mg reduce central subfield thickness (CST) and improve best-corrected visual acuity (BCVA) of participants? What medical problems do participants have after receiving intravitreal injections of brolucizumab 6 mg? Researchers will compare baseline CST and BCVA to those at each post-baseline visit to see if brolucizumab 6 mg works to treat persistent DME.
Participants will:
Receive brolucizumab 6 mg via intravitreal injections following two treatment patterns:
Treatment Pattern 1: every 6 weeks for 5 injections Treatment Pattern 2: every 6 weeks for 3 injections followed by 1 injection after 12 weeks Visit the clinic 8 times for treatment and assessments over the course of 28 weeks
开始日期2024-07-09 |
申办/合作机构 四川省人民医院 [+1] |
TCTR20240924004
Evaluation of Sterility, Stability, and Efficacy of Repackaged Bevacizumab, Aflibercept, Ranibizumab, Brolucizumab, and Faricimab for Intravitreal Administration: An Experimental Study
开始日期2024-04-10 |
申办/合作机构- |
CTRI/2023/06/054105
TOPIC A COMPARATIVE STUDY OF INTRAVITREAL BROLUCIZUMAB 6.0 mg VERSUS 3.6 mg IN MANAGEMENT OF NAIVE CENTRE INVOLVING DIABETIC MACULAR EDEMA
开始日期2023-07-01 |
申办/合作机构- |
100 项与 溴珠单抗 相关的临床结果
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100 项与 溴珠单抗 相关的转化医学
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100 项与 溴珠单抗 相关的专利（医药）
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423
项与 溴珠单抗 相关的文献（医药）2025-03-01·AMERICAN JOURNAL OF OPHTHALMOLOGY
Comparison of Renal Adverse Events Between Intravitreal Anti–Vascular Endothelial Growth Factor Agents: A Meta-Analysis
Review
作者: Jhaveri, Aaditeya ; Balas, Michael ; Kertes, Peter J ; Huang, Ryan S ; Popovic, Marko M ; Muni, Rajeev H
PURPOSE:
To compare the risk of renal adverse events, particularly acute kidney injury (AKI), between intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.
DESIGN:
Meta-analysis.
METHODS:
A systematic literature search was conducted on Ovid Medline, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published from January 2005 to February 2024 involving adult patients receiving anti-VEGF intravitreal injections for age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. The primary outcome was the comparative risk of AKI between anti-VEGF agents and sham injections. Secondary outcomes involved other renal adverse events. Subgroup analyses were conducted by specific disease indications. A random-effects model was used for meta-analysis to estimate risk ratios (RRs) and their 95% confidence intervals, with a P value of <.05 representing statistical significance. Risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB2) tool, and the certainty of evidence was evaluated through the Cochrane Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework.
RESULTS:
A total of 10,031 eyes from 11 RCTs were included. No significant differences were found in the risk of acute or chronic renal conditions, obstructive uropathies, neoplasia, or infectious processes between anti-VEGF agents and sham therapy. AKI was reported in 5.4% (n = 10/185) of patients treated with bevacizumab, 1.3% (n = 6/456) with sham, 1.0% (n = 48/4724) with aflibercept, 0.8% (n = 15/1929) with faricimab, 0.5% (n = 5/1098) with brolucizumab, and 0.3% (n = 5/1639) with ranibizumab. No significant differences in AKI risk were observed between any of the anti-VEGF agents and sham (P > .05 for all comparisons). However, there was an increased risk of patient-reported symptoms with 1.25 mg bevacizumab compared to 2 mg aflibercept (RR = 3.26, 95% CI = 1.07-9.93, P = .04), driven primarily by reports of hematuria: 4.3% (bevacizumab), 0.7% (sham), 0.2% (aflibercept), 0.1% (faricimab), and 0.1% (ranibizumab).
CONCLUSIONS:
US Food and Drug Administration (FDA)-approved intravitreal anti-VEGF agents do not significantly increase the risk of AKI compared to sham injections. Nevertheless, variations in patient-reported renal symptoms were observed across different anti-VEGF drugs. These variations were influenced primarily by differences in hematuria events, which may be a result of differential systemic absorption by these agents. These results underscore the importance of continuous monitoring and pharmacovigilance.
2025-02-01·AMERICAN JOURNAL OF OPHTHALMOLOGY
Submacular Hemorrhage Rates Following Anti-Vascular Endothelial Growth Factor Injections for Exudative Age-Related Macular Degeneration
Article
作者: Kaufmann, Gabriel T. ; Boucher, Nicholas ; Starr, Matthew R. ; Aggarwal, Nitika ; Kaufmann, Gabriel T ; Starr, Matthew R ; Sharma, Chakshu
PURPOSE:
To examine rates of submacular hemorrhage in patients undergoing anti-vascular endothelial growth factor (VEGF) injections, comparing rates between specific anti-VEGF agents.
DESIGN:
Retrospective clinical cohort study.
METHODS:
All patients in the database from January 2015 to November 2023 with a diagnosis of neovascular age-related macular degeneration and accompanying submacular hemorrhage (SMH). SMH prevalence and associated anti-VEGF injection type were analyzed in 140,915 eyes (of which 9107 had SMH) in a nationwide aggregated electronic health care database using chi-square test of proportion. Visual acuity (VA) data was assessed using 2-sample independent t-tests. The primary outcome was rate of SMH per injection type. Secondary datapoints examined were time between SMH diagnosis and last anti-VEGF injection, number of injections before SMH, treatment interval at time of SMH, VA before and at 12 months after SMH, eyes undergoing pars plana vitrectomy (PPV) within 30 days of SMH, and VA before PPV and at 12 months after PPV.
RESULTS:
The last injection type in eyes with SMH was bevacizumab in 3430 (37.8%) eyes, brolucizumab-dbll in 46 (0.51%) eyes, aflibercept in 3221 (35.4%) eyes. Ranibizumab in 2246 (24.7%) eyes, and faricimab-svoa in 155 (1.7%) eyes. Rates of SMH were significantly higher (P ≤ .001) for last injection with bevacizumab compared to every other injection type. Rates of SMH were significantly lower (P = .0004) for last injection with faricimab-svoa or ranibizumab injections each had significantly shorter (mean and standard deviation 48.9 (27.9), P < .02; mean and standard deviation 59.6 (38.2), P = .003, respectively) mean time between SMH diagnosis and last injection than did patients undergoing any other injection. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type among all patients. The number of patients who underwent PPV were 52 (1.51%) for bevacizumab, 4 (8.7%) for brolucizumab-dbll, 58 (1.8%) for aflibercept, 41 (1.8%) for ranibizumab, and 3 (1.9%) for faricimab-svoa. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type in patients undergoing PPV.
CONCLUSIONS:
Faricimab may be more protective than other anti-VEGF injections against SMH in patients with neovascular age-related macular degeneration.
2025-02-01·OPHTHALMOLOGY
MERLIN: Two-Year Results of Brolucizumab in Participants with Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid
Article
作者: Heier, Jeffrey S. ; Khanani, Arshad M ; Wykoff, Charles C ; Jaffe, Glenn J ; Brown, David M ; Heier, Jeffrey S ; Wykoff, Charles C. ; Jaffe, Glenn J. ; Adiguzel, Eser ; Brown, David M. ; Khanani, Arshad M.
PURPOSE:
To report the safety and efficacy of brolucizumab (Beovu) 6 mg versus aflibercept (Eylea) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the week 52 up to week 104.
DESIGN:
Multicenter, randomized, double-masked phase 3a study.
PARTICIPANTS:
Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-VEGF treatment).
METHODS:
Study eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks or until study termination.
MAIN OUTCOME MEASURES:
All available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]) and safety data up to study termination, including data up to week 104 for those participants who completed the study before its termination. All P values after week 52 were nominal and reflect observed data for the efficacy analyses.
RESULTS:
Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to week 104 (least squares mean difference, -0.4 ETDRS letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept (P = 0.7762), and a greater proportion of eyes were fluid free at week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9-37.3; P < 0.001) in eyes treated with brolucizumab versus aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab versus 6.1% (0% and 0.6%) for aflibercept.
CONCLUSIONS:
Consistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change, with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab versus aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks after the loading regimen.
FINANCIAL DISCLOSURE(S):
Proprietary or commercial disclosure may be found after the references.
111
项与 溴珠单抗 相关的新闻（医药）2025-02-11
·抗体圈
罗氏在眼科药物大蓝海中再下一城。
继在1月底公告全球首款眼科双抗Vabysmo在2024年大卖44亿美元，2月4日罗氏的Susvimo（100mg/mL雷珠单抗注射液）获得FDA的批准，用于治疗糖尿病性黄斑水肿（DME），眼科已经俨然成为了带动这家MNC业绩增长的“利剑”之一。
眼科疾病虽然不同肿瘤，但它却是肿瘤常见的单抗——VEGF单抗的主要用武之地之一。在黄斑变性（Macular Degeneration），几大VEGF单品一直在瓜分着这近百亿的市场，相对来说，一个普通ADC药物的销售峰值给到20亿美元左右是正常现象，典例便是经典的HER2 ADC——T-DM1，其2023年销售额是22.2亿美元（相比21年仅增长5000万美元左右，目前趋势见顶）。
目前肿瘤管线市场正在被中国BD批发基地彻底改变格局，愈发红海。也因此，前瞻的投资者和从业人员可以把目光放在其他一些大单品的病种之上，寻找更加多元化的机会。
挖掘眼科创新品种的机会，刻不容缓。
01
黄斑变性与大单品
黄斑位于视网膜中心，直径约5毫米，富含视锥细胞（负责精细视觉和色觉），是视力最敏锐的区域。其功能包括阅读、驾驶、识别人脸等中心视力。因此，它如果变性，对视网膜的影响是巨大的。
而对于黄斑视网膜变性而言，分为干性和湿性，其中湿性视网膜黄斑变性，与新生血管以及VEGF因子息息相关。
根据综述《眼部抗VEGF药物缓释系统研究进展》，视网膜色素上皮细胞、血管内皮细胞等均可产生血管内皮生长因子(即VEGF)，VEGF的作用主要是增加现有血管的通透性和促进新生血管生成，过量表达的VEGF促使脂质和蛋白质等大分子从血管逃逸到视网膜，形成血管周围组织水肿，发生糖尿病性黄斑水肿(diabetic macular edema，DME)；另一方面，新生血管性年龄相关性黄斑变性(neovascular age-related macular degeneration，nAMD)中过量的VEGF促进脉络膜新生血管生成，新生血管向上生长突破Bruch膜和RPE导致出血和水肿，最终形成纤维瘢痕破坏黄斑中心的感光细胞。
（图片来源：CG医疗咨询）
简单来说，如果要解决这个问题，就要逆转新生血管的形成，而要逆转新生血管的形成，就必须要消灭过多的VEGF因子，因此，就需要VEGF抗体，注射进眼内了。VEGF抗体除了在肿瘤之外，也组成了DME和nAMD两大眼科适应症疾病进展的可靠力量。
而其中较为著名的是罗氏的雷珠单抗，诺华的Beovu以及拜耳的阿柏西普。这个市场能够有多么巨大呢？2020年雷珠单抗的销售额为33.77亿美元，而阿柏西普的销售额自2015年开始便反超雷珠单抗，2022年其销售额达到了96.47亿美元，2023年略有下滑，但仍然维持在90亿美元以上。
雷珠单抗在2006年被FDA获批上市，阿柏西普2011年获批上市，目前二者都面临着专利悬崖，生物类似药厂家们跃跃欲试。而下一代创新药，也在紧锣密鼓准备着进行迭代。
（图片来源：ADVERUM官网PPT）
这里根据ADVERUM官网PPT的数据，光是wet-AMD单个眼科适应症，患者数量上美国就有150万名，而世界范围内有200万名。在市场方面，2025年市场为90个亿美元左右，预计2035年将会发展到130个亿美元。
罗氏于近日宣布，其眼科新药Susvimo被FDA获批上市，用于治疗糖尿病性黄斑水肿（DME），该药是雷珠单抗的创新剂型，为一款可再填充的眼部植入物，可通过一次性门诊手术植入眼内，然后进行雷珠单抗的注射，该药物的创新优势在于给药周期的大大延长，从传统雷珠单抗的1月1次注射到了半年1次注射，大大提高了患者的依从性。
（图片来源：Prescribing Information- Susvimo）
02
新锐biotech正在冲击
不止老牌MNC例如罗氏在想法设法完成迭代，新锐biotech也在用自己的方式去完成迭代。其中药物递送系统的迭代是较为主流的方向，这里借用沙利文的一张图表总结来进行较为直观的呈现。
（图片来源：沙利文报告）
公司方面，笔者认为近日最值得关注的自然是Eyepoint（RYPT）近日的临床试验成功。与罗氏发布FDA获批通知的同一天，EYPT宣布其正在进行的II期临床——VERONA取得了积极的6个月结果，管线正是其主打管线EYP-1901。
eyepoint有看点的地方在于其DURAVYU（沃罗尼布玻璃体内植入剂）专利递送剂型以及非常有意思的不是VEGF的药物——伏罗尼布（贝达药业的单品）。
先说递送系统，Eyepoint的递送平台名为Durasert E，目的就是为了创造恒定速率的给药输送装置，众所周知，给药注射后最糟心的便是药物达峰时间太短，随后代谢太快。而该平台所生产的给药装置目的是能够做到恒定速率给药（即所谓的零级释放），通过大大延缓药物释放速度，来减少给药的频次。EYP-1901采用该技术可实现约9个月的药物缓释。
其次是它们选择的药物——沃罗尼布，它是一款酪氨酸激酶抑制剂（TKI），众所周知，其一般作为NSCLC的靶向药存在。
（图片来源：eyepoint官网PPT）
之所以选择它，是因为它对VEGF的各受体亚型均具有高选择性。
这次临床试验，它选择了大单品阿柏西普作为对照组。治疗组的剂量组为1.34mg与2.7mg，这里我们选择2.7mg去看，DURAVYU的2.7mg剂量组显示出最佳矫正视力 (BCVA) 和中央视网膜厚度 (CST) 的持续改善。在可量化的疗效方面，通过光学相干断层扫描 (OCT) 测量，与基线相比：
1.BCVA 提高了 +7.1 个字母。
2.与基线相比，CST改善了75.9微米，这意味着DURAVYU患者的眼睛与阿柏西普对照组相比干燥程度提高了74%。
此外，截至第 24 周，EYP-1901的2.7mg组有73%的眼睛未使用补充剂，而阿柏西普对照组中这一比例为 50%，这强调了积极疗效结果是由EYP-1901治疗而不是补充注射推动的。
其三期临床预计将于今年年底启动。百亿市场里，EYP-1901未来能切出多少蛋糕来，会不会再创阿柏西普的神话，是全球眼科市场五年内最大的悬念之一。此外，也关系着Eyepoint未来的命运走向。
除了EYPT近期的新型给药载体系统值得关注之外，一些更为新型的疗法也非常值得一看，其中4D Molecular Therapeutics（FDMT）的AAV载体疗法治疗湿性年龄相关性黄斑变性（wet-AMD）恰巧在最近两日出了其核心管线——4D-150临床2b期试验的顶线数据，今晚就能观察到股价的波动。
对于AAV疗法在这个领域的优势而言，其主打的是在做到不亚于阿柏西普疗效条件下，减少患者的注射负担，即减少患者眼内注射的给药频次。
这里给出的也是这方面最关键的数据：与2mg Q8W剂量-频次下的 阿柏西普相比，3E10 vg/眼剂量下的（这里vg指的是病毒颗粒的单位，3E10指的是3的10次方）的注射负担减少了83%，70%的患者需要0-1次补充注射，57%的患者在52周内无需注射。如图所示，在整个试验组和阿柏西普对照组相比，之后累积注射次数方面，每位患者的注射次数为0.97次 VS 6次，减少了83%的注射负担。
患者眼内注射依从性不好是老生常谈，如今不管是改剂型还是开发长效的AAV疗法，都是在改善患者治疗的依从性，可以让患者注射没有那么的痛苦。
当然，FDMT也有它相同类型管线的对手——adverum的治疗wet-AMD的AAV疗法管线已经在1月份公布了III期临床试验的设计。关于两家biotech更加详细的对比，未来有机会专门写一篇关于AAV疗法治疗眼科药物的深度文章。
03
国内市场
一方面，在国内市场的销售端，国内的药物中，康柏西普是国内药企上个时代创新的代表，该药由康弘药业历史十年，耗资十亿开发出来的单品，其于2013年获批上市，在国内的销售额2023年达到了19.4亿元人民币，上市近十年，还能同比增长47.1%，2013-2024年一季度，康柏西普合计销售约达到了97亿元。
另一方面，在国内市场的研发端，首先是贝达药业在和Eyepoint合作，充当卖水人的角色，提供伏罗尼布，也因此，贝达药业获得了该药在国内商业化的权利。
biotech之中，信达在眼科药物领域深耕众人皆可看到。IBI302和IBI324便是两条很有意思的管线。
IBI302为双特异性融合蛋白，靶点为C3b + C4b + Complement receptors + VEGF。N端为VEGF结合域，能够与VEGF家族结合阻断VEGF介导的信号通路，抑制血管内皮细胞的生存、增殖，从而抑制血管新生，降低血管渗透性，减少血管渗漏；C端为补体结合域，能够通过特异性结合C3b和C4b，抑制补体经典途径和旁路途经的激活，减轻补体活化介导的炎症反应。
一边抑制血管增生，一边抑制可能发生的炎症反应，其真正在VEGF单抗的基础上大大推进了一步。
IBI324是信达生物自主研发的抗Ang2 + VEGF-A双靶点特异性重组全人源化抗体：N端能够阻断VEGF-A介导的信号通路，抑制血管内皮细胞的生存、增殖，从而抑制血管新生，减少新生血管渗漏；C端为Ang-2结合域，为信达自主筛选获得的抗Ang-2，不结合Ang-1，抑制Ang-2与Tie-2受体结合，改善对其他炎症因子的敏感性，进一步稳定血管，抑制血管渗漏。
结语：这个市场是真正意义上的百亿市场，现在的蓄力是为了之后的爆发，双抗和缓释给药系统能在单抗之上完成效率如何的迭代，能够吃掉多少前代市场，就看之后它们III期临床的疗效，能否给出比前代单抗例如阿柏西普更优异的数据了，我们不妨期待一下。
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抗体药物偶联物上市批准
2025-01-13
NORTH CHICAGO, IL and ROCKVILLE, MD, USA I January 13, 2025 I
AbbVie (NYSE:
ABBV
) and REGENXBIO Inc. (Nasdaq:
RGNX
) today announced updates to the ABBV-RGX-314 clinical program.
ABBV-RGX-314 in Wet Age-Related Macular Degeneration (wet AMD), Subretinal Delivery
Data from the ATMOSPHERE
®
and ASCENT
™
pivotal trials evaluating the safety and efficacy of the subretinal delivery of ABBV-RGX-314 in patients with wet AMD are expected in 2026.
ABBV-RGX-314 in
Diabetic Retinopathy (DR), Suprachoroidal Delivery
AbbVie and REGENXBIO will plan a Phase 3 clinical program. The clinical program will utilize the in-office SCS Microinjector
®
to deliver gene therapy to the suprachoroidal space of the eye.
“Retinal diseases are progressive, with wet AMD and DR among the leading causes of blindness,” said Michael Robinson, M.D., vice president, global head of ophthalmology clinical development, AbbVie. “More treatment options are needed to help relieve the current treatment burden of chronic, frequent dosing. We are excited to continue moving closer to our goal of delivering an additional treatment option to patients with wet AMD and DR in hopes of addressing their significant unmet needs.”
“ABBV-RGX-314 has the potential to help millions of people living with wet AMD and DR, globally, who are facing these debilitating diseases,” said Curran Simpson, president and chief executive officer, REGENXBIO. “Together with AbbVie, we are excited to continue developing ABBV-RGX-314 as the first potential one-time gene therapy for wet AMD and DR.”
About ABBV-RGX-314
ABBV-RGX-314 is being investigated as a potential one-time treatment for wet AMD, diabetic retinopathy and potentially other chronic retinal conditions. ABBV-RGX-314 consists of the NAV
®
AAV8 vector, which encodes an antibody fragment designed to inhibit vascular endothelial growth factor (VEGF). ABBV-RGX-314 is believed to inhibit the VEGF pathway by which new, leaky blood vessels grow and contribute to the accumulation of fluid in the retina.
1
AbbVie and REGENXBIO are advancing the development of two separate routes of administration of ABBV-RGX-314 to the eye, through a standardized subretinal delivery procedure as well as delivery to the suprachoroidal space. REGENXBIO has licensed certain exclusive rights to the SCS Microinjector
®
from Clearside Biomedical, Inc. to deliver gene therapy treatments to the suprachoroidal space of the eye.
About Wet AMD
Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina.
2
Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to two million people living with wet AMD in these geographies alone.
3
Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients.
4
These therapies, however, require life-long repeated intraocular injections, to maintain efficacy.
5,6
Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time.
7
About Diabetic Retinopathy
Diabetic retinopathy (DR) is the leading cause of vision loss in adults between 24 and 75 years of age worldwide.
8
DR affects nearly 10 million people in the United States alone.
9
The spectrum of DR severity ranges from non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR).
4
As DR progresses, a large proportion of patients develop vision threatening complications, including diabetic macular edema (DME) and neovascularization that can lead to blindness.
10
Current treatment options for patients with NPDR typically include “watchful waiting” or anti-VEGF treatment. For patients with PDR, current treatment options include anti-VEGF treatment or retinal laser; surgical treatment may be required for advanced PDR.
2
About AbbVie
AbbVie’s mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. AbbVie strives to have a remarkable impact on people’s lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in AbbVie’s Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at
www.abbvie.com
. Follow @abbvie on
LinkedIn,
Facebook
,
Instagram
,
X (formerly Twitter)
, and
YouTube.
ABOUT REGENXBIO Inc.
REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for rare and retinal diseases, including RGX-202 for the treatment of Duchenne, ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, and RGX 121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO’s AAV Therapeutic platform, including Novartis’ ZOLGENSMA
®
for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit
www.regenxbio.com
.
1
Penn JS, Madan A, Caldwell RB, et al. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res. 2008;27(4):331-71.
2
Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932-6.
3
Decision Resources Group, 2019
4
Alexandru MR, Alexandra NM. Wet age related macular degeneration management and follow-up. Rom J Ophthalmol. 2016;60:9–13.
5
AAO PPP. Preferred Practice Patterns: Age related macular degeneration. American Academy of Ophthalmology. 2019.
6
Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2020;127(1):72-84.
7
Holz FG et al. Br J Ophthalmol. 2015;99:220.
8
Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376(9735):124–36.
9
Lundeen EA, Burke-Conte Z, Rein DB, Wittenborn JS, Saaddine J, Lee AY, Flaxman AD. Prevalence of Diabetic Retinopathy in the US in 2021. JAMA Ophthalmology. 2023;141(8):747-754.
10
Berrocal MD, Alexandra Acabá. Current Management of Diabetic Retinopathy, 2018
SOURCE:
AbbVie
临床3期基因疗法
2024-12-23
关注并星标CPHI制药在线
2024年12月21日，诺华公司宣布其新药布西珠单抗注射液的第三项适应症已在中国国家药监局药品审评中心（CDE）提交上市申请。这标志着布西珠单抗在成功应用于治疗湿性年龄相关性黄斑变性（wAMD）和糖尿病黄斑水肿（DME）之后，于中国市场迎来了其第三项适应症申报的又一重要进展。尽管具体适应症尚未公示，但根据公开资料推测，本次申报的适应症极有可能是增殖期糖尿病性视网膜病变（PDR）。
（点击小图看大图）
药物研发背景
糖尿病性视网膜病变（DR）是糖尿病最常见的微血管并发症之一，也是导致工作人群不可逆性视力损伤的首要原因。PDR作为DR的晚期阶段，以视网膜出现异常新生血管为标志，并可发生玻璃体积血、牵引性视网膜脱离、新生血管性青光眼等并发症，严重危害患者的视觉功能。据统计，全球约有4.63亿糖尿病患者，其中约三分之一可能患有DR，而PDR患者的比例更是不容忽视。
PDR的治疗一直是眼科医学研究的重点。传统疗法主要包括全视网膜激光光凝治疗，尽管这种疗法在一定程度上能够控制病情，但患者往往需要多次治疗，且视力改善有限。因此，开发新型、有效的治疗药物显得尤为重要。然而，现有的抗VEGF药物，如雷珠单抗、康柏西普等，虽然在一定程度上能够控制DR的进展，但仍然存在一些不足。例如，这些药物通常需要每月或每两月进行玻璃体腔内注射，频繁的治疗和随访要求给患者和医疗资源都带来了沉重负担。此外，由于随访和治疗不足，许多患者无法获得持续有效的积液消退，治疗效果并不理想。因此，研发新一代抗VEGF药物，以提高治疗效果、减少治疗频率、降低患者负担，成为眼科医学界的重要课题。
新药布西珠单抗作用机制和优势
布西珠单抗（Brolucizumab，也称为RTH258）是诺华公司研发的一种新型人源化单链抗体片段，分子量仅为26kDa，是一种全VEGF-A抑制剂。与现有的抗VEGF药物相比，布西珠单抗具有更高的亲和力、更强的组织渗透力和更小的全身副反应。这些特点使得布西珠单抗在治疗DR方面具有显著的优势。
布西珠单抗的作用机制主要是通过抑制VEGF-A的活性，从而阻断新生血管的形成，减少血管的通透性，达到控制DR进展的目的。由于布西珠单抗的分子量较小，它能够更快地渗透到视网膜组织中，与VEGF-A结合并抑制其活性。此外，布西珠单抗的亲和力高，能够更有效地与VEGF-A结合，从而延长药物在视网膜组织中的滞留时间，提高治疗效果。
除了作用机制上的优势外，布西珠单抗在治疗DR方面还具有其他显著的优势。首先，布西珠单抗能够更早地吸收视网膜内积液和视网膜下积液，从而减轻视网膜水肿，改善患者的视力。其次，布西珠单抗的注射频率较低，负荷期后只需要每3个月注射一次，这大大降低了患者的治疗负担和医疗资源消耗。此外，布西珠单抗在持续改善解剖结构方面也具有明显的优势，能够更有效地控制DR的进展，减少并发症的发生。
布西珠单抗的临床应用不仅限于DR的治疗。由于其具有广泛的抗血管生成作用，布西珠单抗还可能用于其他与新生血管形成相关的眼科疾病的治疗，如湿性年龄相关性黄斑变性（wAMD）、糖尿病黄斑水肿（DME）等。这些疾病的发病机制与DR相似，都与VEGF的异常表达密切相关。因此，布西珠单抗在这些疾病的治疗中也具有广阔的应用前景。
临床研究
布西珠单抗的临床数据为其在治疗DR方面的疗效和安全性提供了有力支持。一项全球3期注册研究（CONDOR研究）评估了布西珠单抗6mg治疗PDR的疗效。该研究纳入了全球范围内的PDR患者，其中包括了来自中国的大量患者。研究结果显示，布西珠单抗在PDR患者中维持视力显著优于传统疗法（全视网膜激光光凝治疗）。
在CONDOR研究的54周时，布西珠单抗组的患者中无PDR者比例是对照组的近三倍（63.8% vs 22.4%）。此外，布西珠单抗组的患者在最佳矫正视力（BCVA）和糖尿病性视网膜病变严重程度（DRSS）评分方面也表现出更好的改善效果。这些结果表明，布西珠单抗在治疗PDR方面具有显著的疗效和安全性。
值得注意的是，在中国人群中，布西珠单抗的疗效和安全性与整体人群相一致。与全视网膜激光光凝治疗组相比，布西珠单抗组的患者在BCVA和DRSS评分方面表现出更好的改善效果，且更低比例的患者存在PDR、累及黄斑中心的DME以及威胁视力的并发症。这些结果进一步证实了布西珠单抗在治疗中国PDR患者中的疗效和安全性。
此外，布西珠单抗的注射频率也较低，负荷期后只需要每3个月注射一次。在CONDOR研究中，布西珠单抗组的患者在负荷期接受每6周一次的布西珠单抗治疗，共3次；在维持期，治疗间隔延长至12周，在48周后可根据疾病活动度评估延长治疗间隔（每次延长6周），最多延长至24周。若维持期内出现病情恶化则将治疗间隔再次缩短至每6周一次。这种灵活的注射方案使得布西珠单抗在治疗DR方面具有更高的患者依从性和更低的医疗资源消耗。
布西珠单抗注射液价值
从市场角度来看，DR作为全球范围内最常见的微血管并发症之一，具有庞大的患者群体和广阔的市场需求。据统计，全球约有4.63亿糖尿病患者，其中约三分之一可能患有DR。在中国，随着人口老龄化和生活方式的改变，DR的发病率也在逐年上升。因此，布西珠单抗注射液的市场前景十分广阔。从病患数量来看，DR患者数量庞大，且呈现出年轻化的趋势。许多患者在确诊时已经进入DR的晚期阶段，如PDR，面临着严重的视力损失和并发症的风险。布西珠单抗注射液的上市将为这些患者提供新的治疗选择，有望提高他们的生活质量，减少并发症的发生。据市场研究数据显示，全球眼科药物市场规模持续增长，预计到2026年将达到数十亿美元。在中国市场，随着"十四五"眼健康政策的推动和眼科医疗水平的提高，布西珠单抗注射液的市场需求将进一步扩大。
结语
诺华新药布西珠单抗注射液的第三项适应症在华申报上市，标志着该药物在治疗增殖期糖尿病性视网膜病变（PDR）方面取得了重要进展。布西珠单抗以其独特的作用机制、显著的疗效和安全性，为DR患者带来了新的治疗选择。
参考文献：
1.中国国家药监局药品审评中心(CDE)网站.
END
【智药研习社近期直播】
来源：CPHI制药在线
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投稿邮箱：Kelly.Xiao@imsinoexpo.com
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100 项与 溴珠单抗 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 糖尿病性黄斑水肿 | 日本 | 2020-03-25 | |
| 黄斑变性 | 日本 | 2020-03-25 | |
| 年龄相关性黄斑变性 | 加拿大 | 2020-03-12 | |
| 湿性年龄相关性黄斑变性 | 美国 | 2019-10-07 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 息肉状脉络膜血管病 | 临床3期 | 韩国 | 2023-02-06 | |
| 肥厚型脉络膜新生血管病变 | 临床3期 | - | 2023-01-01 | |
| 伴有糖尿病的增殖性视网膜病变 | 临床3期 | 美国 | 2020-11-19 | |
| 伴有糖尿病的增殖性视网膜病变 | 临床3期 | 美国 | 2020-11-19 | |
| 伴有糖尿病的增殖性视网膜病变 | 临床3期 | 美国 | 2020-11-19 | |
| 伴有糖尿病的增殖性视网膜病变 | 临床3期 | 美国 | 2020-11-19 | |
| 伴有糖尿病的增殖性视网膜病变 | 临床3期 | 中国 | 2020-11-19 | |
| 伴有糖尿病的增殖性视网膜病变 | 临床3期 | 日本 | 2020-11-19 | |
| 伴有糖尿病的增殖性视网膜病变 | 临床3期 | 日本 | 2020-11-19 | |
| 伴有糖尿病的增殖性视网膜病变 | 临床3期 | 日本 | 2020-11-19 |
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临床结果
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 |
|---|
临床4期 | 52 | (Brolucizumab 6 mg Loading) | 積蓋夢鹹蓋鑰構淵網構(壓觸艱範選衊鹽網廠構) = 淵齋鹹繭獵觸糧憲鑰蓋 鹽醖獵蓋鹹繭壓遞醖鹽 (網積淵淵繭築鑰簾構憲, 構襯願壓鏇簾齋壓鬱網 ~ 築繭積積蓋製築憲顧繭) 更多 | - | 2025-01-27 | ||
(Brolucizumab 6 mg Non-loading) | 積蓋夢鹹蓋鑰構淵網構(壓觸艱範選衊鹽網廠構) = 願遞遞齋艱網淵構鹽壓 鹽醖獵蓋鹹繭壓遞醖鹽 (網積淵淵繭築鑰簾構憲, 鹹鏇膚鹽選淵製膚鏇選 ~ 廠衊範鏇膚糧蓋選獵窪) 更多 | ||||||
临床4期 | 105 | 壓鬱衊選蓋襯獵襯膚壓(窪壓鏇製蓋範鬱鑰簾淵) = 願觸衊憲鬱選鑰餘憲選 窪夢鏇繭網製積獵選構 (齋廠網獵繭廠顧鏇願製, 簾鏇選積蓋廠觸蓋簾築 ~ 鏇糧顧構齋繭憲艱獵獵) 更多 | - | 2024-12-10 | |||
HOBBY (NEWS) 人工标引  | 临床3期 | - | 6mg布西珠单抗 | 顧糧齋壓壓築顧顧製範(窪憲夢遞繭選廠鹽製顧) = 鏇遞觸齋簾壓獵夢構憲 積積鑰遞憲繭衊鏇齋蓋 (淵壓艱觸觸選衊夢廠繭, 0.82) 更多 | 积极 | 2024-11-25 | |
2mg阿柏西普 | 顧糧齋壓壓築顧顧製範(窪憲夢遞繭選廠鹽製顧) = 醖鹹顧憲範鏇醖餘壓願 積積鑰遞憲繭衊鏇齋蓋 (淵壓艱觸觸選衊夢廠繭, 0.82) 更多 | ||||||
临床3期 | - | 6mg布西珠单抗 | 鹽醖構鑰廠齋繭範壓憲(築遞淵鹹願夢願蓋構襯) = 鹽膚膚願餘顧膚製膚窪 鹽襯壓簾衊鬱衊構壓淵 (廠鏇鹽夢壓鏇鏇餘壓膚 ) 更多 | 非劣 | 2024-11-25 | ||
2mg阿柏西普 | 鹽醖構鑰廠齋繭範壓憲(築遞淵鹹願夢願蓋構襯) = 餘鹽衊衊憲簾願構鬱餘 鹽襯壓簾衊鬱衊構壓淵 (廠鏇鹽夢壓鏇鏇餘壓膚 ) 更多 | ||||||
临床3期 | - | (整体人群) | 觸築鹽願壓廠築構繭鹽(獵獵鹽獵鹹顧顧顧壓鬱) = 夢獵積廠構鹹鹽襯獵網 廠鏇膚餘窪醖觸窪鏇鹹 (艱選壓遞糧膚鑰顧衊繭 ) | 积极 | 2024-11-25 | ||
全视网膜激光光凝 (整体人群) | - | ||||||
临床3期 | 295 | 範夢積壓構製製淵艱獵(醖廠繭願壓築窪憲夢夢) = 鏇夢顧選廠鑰糧鑰製鬱 壓壓構廠糧鬱醖鏇襯膚 (齋憲衊糧觸壓膚獵鑰積, 簾網廠淵顧餘糧獵齋夢 ~ 繭壓鏇醖艱壓簾憲獵襯) 更多 | - | 2024-11-07 | |||
EURETINA2024 人工标引 | N/A | 200 | (four-week intervals) | 膚鑰蓋製鬱顧構淵鏇醖(鏇夢蓋構選艱鹽製選製) = 憲製餘壓簾餘蓋選願憲 獵遞夢鏇遞醖齋鹹廠齋 (構齋衊鑰窪鹹獵選鬱壓 ) | 积极 | 2024-09-19 | |
(six-week intervals) | 膚鑰蓋製鬱顧構淵鏇醖(鏇夢蓋構選艱鹽製選製) = 遞糧壓齋網築範窪壓夢 獵遞夢鏇遞醖齋鹹廠齋 (構齋衊鑰窪鹹獵選鬱壓 ) | ||||||
EURETINA2024 人工标引 | N/A | 29 | 鹽衊觸鹽餘憲夢糧醖衊(簾壓醖簾願鬱餘範選網) = 衊憲遞廠衊廠積選糧淵 膚網醖遞廠簾鹹製衊齋 (窪窪鹽鹹簾壓繭廠淵鬱 ) 更多 | 积极 | 2024-09-19 | ||
Brolucizumab 6mg | 鹽衊觸鹽餘憲夢糧醖衊(簾壓醖簾願鬱餘範選網) = 廠憲製選壓齋艱範鬱網 膚網醖遞廠簾鹹製衊齋 (窪窪鹽鹹簾壓繭廠淵鬱 ) 更多 | ||||||
N/A | - | 顧鏇繭窪蓋壓憲襯膚糧(壓遞遞製襯壓淵顧鬱構) = 7 female patients with asymptomatic iritis (8.9% of treated eyes) 醖窪簾構壓醖齋製淵獵 (夢淵淵艱範選鹽鏇顧齋 ) 更多 | - | 2024-09-19 | |||
N/A | - | - | 餘廠簾鏇醖淵餘糧願蓋(範憲夢鏇積鹹網構繭簾) = 3 eyes (0.37%/eye and 0.74%/injection) developed intraocular inflammation 簾餘鏇壓餘憲鹽願艱襯 (觸醖觸憲範糧鬱網構簾 ) 更多 | - | 2024-09-19 |
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