Faricimab

6月28日，罗氏宣布，两款新药的上市申请获欧洲药品管理局（EMA）人用药品委员会（CHMP）的积极意见，包括Vabysmo（法瑞西单抗）用于治疗视网膜静脉阻塞（RVO）继发黄斑水肿引起的视力障碍的新适应症以及PiaSky（可伐利单抗）用以治疗阵发性睡眠性血红蛋白尿症（PNH）患者的新药上市申请。预计欧盟委员会将在不久的将来就这两项批准做出最终决定。 ▌Vabysmo（法瑞西单抗） Vabysmo（法瑞西单抗）是罗氏开发的一款靶向血管生成素2（Ang2）和血管内皮生长因子A（VEGFA）的双特异性单克隆抗体。2022年9月19日，已在欧盟获批两项适应症，分别是治疗新生血管性（湿性）年龄相关性黄斑变性（nAMD）以及糖尿病性黄斑水肿 (DME) 引起的视力障碍。 此次申报的是第三项适应症，如果获得批准，Vabysmo将是欧盟近100万RVO患者可用的首个也是唯一的双特异性抗体疗法。 CHMP的决定是基于III期BALATON和COMINO研究的完整72周数据，该研究评估了Vabysmo在1200多名分支和中央RVO (BRVO和CRVO)引起的黄斑水肿患者中的疗效。在这两项研究中，Vabysmo显示出早期和持续的视力改善，其效果非劣效于阿柏西普，并且持续维持视网膜干燥。Vabysmo耐受性良好，安全性与先前的研究一致。 RVO是导致失明的第二大常见原因，根据血管阻塞的部位其可分为视网膜分支静脉阻塞（BRVO）和视网膜中央静脉阻塞（CRVO）两种，其中前者占80%以上。视网膜静脉发生阻塞后，血液回流受阻，视网膜血管发生渗出，并发黄斑水肿及视网膜内出血，导致视力下降。全球约2800万成年人（主要是60岁及以上成年人）受RVO所累。现有疗法主要为激光治疗、抗VEGF治疗及手术治疗。 目前全球共5款眼部注射制剂用于治疗RVO，其余4款分别为阿柏西普（再生元/拜耳）、康柏西普（康弘药业）、雷珠单抗（罗氏/诺华）和Ozurdex（艾伯维），其中除Ozurdex外均为VEGF/VEGFR靶向药物。 ▌PiaSky（可伐利单抗） PNH是一种罕见且危及生命的血液疾病，全世界约有2万人受到影响。PNH患者的红细胞被补体系统(先天免疫系统的一部分)破坏，从而导致贫血、疲劳和血栓等症状，并可能导致肾脏疾病。C5抑制剂可阻断部分补体系统级联反应，已被证明对治疗PNH有效。 PiaSky（可伐利单抗）是一种靶向补体蛋白C5的重组人源化IgG1亚型单克隆抗体，能特异性地与补体蛋白C5结合，从而抑制C5裂解为C5a和C5b，阻止末端补体复合物C5b-9的产生，抑制补体途径免疫反应。PiaSky可以在血液中循环使用，使药物能够多次结合并抑制C5蛋白，并且在少量药物的情况下在体内发挥更长久的作用。在治疗的第一个月进行初始静脉输注和每周皮下注射（SC）负荷剂量之后，每4周SC一次。 如果此次获得欧盟委员会批准，PiaSky将成为欧盟首个每月皮下注射PNH治疗药物，在经过适当的培训后，患者可以选择自我管理。这可能为目前需要定期静脉（IV）输注C5抑制剂患者提供另一种选择，可能有助于减轻治疗负担和对PNH患者及其护理人员生活的干扰。 CHMP的推荐是基于之前一项在未接受过C5抑制剂治疗的PNH患者中进行的III期COMMODORE 2研究结果。研究结果表明，每四周SC注射一次PiaSky，实现了疾病控制，并且耐受性良好。PiaSky的安全性与eculizumab相当，eculizumab是一种现有的C5抑制剂，每两周静脉注射一次。使用PiaSky治疗的患者的不良事件发生率与使用eculizumab治疗的患者相似(分别为78%和80%)。申请资料包还包括来自另外两项III期研究的支持性数据：COMMODORE 1研究，用于从接受此前已批准C5抑制剂切换的PNH患者，以及COMMODORE 3研究，用于中国新接受C5抑制剂治疗的PNH患者。 PiaSky已于今年2月7日在中国实现全球首批并于今年6月22日获美国FDA批准上市。 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。

Positive recommendation is based on two Phase III studies. In addition to robust retinal drying with Vabysmo, these data show early and sustained vision improvements, which are non-inferior to aflibercept If approved, Vabysmo would be the first and only bispecific antibody treatment available for the nearly one million people with RVO in the European UnionVabysmo is already approved in the US and Japan for RVO and in more than 95 countries around the world for people living with nAMD and DME Basel, 28 June 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the extension of the Vabysmo® (faricimab) marketing authorisation to include the treatment of visual impairment due to macular edema secondary to retinal vein occlusion (RVO). A final decision regarding the approval is expected from the European Commission in the near future. “This CHMP recommendation represents an important step towards bringing Vabysmo to even more patients living with vision loss in Europe,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Recognising the disruptive impact retinal vein occlusion can have on the everyday lives and independence of these patients, we hope that Vabysmo will offer a new treatment option that can effectively help preserve and improve their vision.” The CHMP decision is based on full 72-week data from the Phase III BALATON and COMINO studies evaluating Vabysmo in more than 1,200 people with macular edema due to branch and central RVO (BRVO and CRVO).1,2 In both studies, Vabysmo demonstrated early and sustained vision improvements non-inferior to aflibercept, and robust retinal drying. Vabysmo was well tolerated and the safety profile was consistent with previous studies.3 Current available treatments for RVO are typically given every one to two months. 4,5 Vabysmo was first approved for RVO by the United States Food and Drug Administration in October 2023 and by the Japan Ministry of Health, Labour and Welfare in March 2024.6-8 It is also approved in more than 95 countries around the world for people living with neovascular or ‘wet’ age-related macular degeneration (nAMD) and diabetic macular edema (DME).6,8-11 Roche has the broadest retina pipeline in ophthalmology. Led by science and informed by insights from people with eye conditions, Roche is committed to saving people’s eyesight from the leading causes of vision loss through pioneering treatments. About retinal vein occlusion (RVO)RVO is the second most common cause of vision loss due to retinal vascular diseases. It affects an estimated 28 million adults globally, mainly those aged 60 or older, and can lead to severe and sudden vision loss.12,13 The level of angiopoietin-2 (Ang-2) is elevated in RVO and it is thought that increased Ang-2 expression drives disease progression.14,15 RVO typically results in sudden, painless vision loss in the affected eye because the vein blockage restricts normal blood flow in the affected retina, resulting in ischemia, bleeding, fluid leakage and retinal swelling called macular edema.13,16,17 Currently, macular edema due to RVO is typically treated with repeated intravitreal injections of anti-vascular endothelial growth factor therapies.16 There are two main types of RVO: branch RVO, which affects more than 23 million people globally and occurs when one of the four smaller ‘branches’ of the main central retinal vein becomes blocked; and central RVO, which is less common, affecting more than four million people worldwide, and occurs when the eye’s central retinal vein becomes blocked.12,17 About the BALATON and COMINO studies1,2BALATON (NCT04740905) and COMINO (NCT04740931) were two randomised, multicentre, global Phase III studies evaluating the efficacy and safety of Vabysmo®️ (faricimab) compared to aflibercept. For the first 20 weeks, patients were randomised 1:1 to receive six monthly injections of either Vabysmo (6.0 mg) or aflibercept (2.0 mg). From weeks 24-72, all patients received Vabysmo (6.0 mg) up to every four months using a treat-and-extend dosing regimen. The BALATON study was conducted in 553 people with branch retinal vein occlusion. The COMINO study was conducted in 729 people with central retinal or hemiretinal vein occlusion. The primary endpoint of each study was the change in best-corrected visual acuity from baseline at 24 weeks. Secondary endpoints included change in central subfield thickness and drying of retinal fluid from baseline over time up to week 24. About the Vabysmo® (faricimab) clinical development programmeRoche has a robust Phase III clinical development programme for Vabysmo. The programme includes AVONELLE-X (NCT04777201), an extension study of TENAYA (NCT03823287) and LUCERNE (NCT03823300), evaluating the long-term safety and tolerability of Vabysmo in neovascular or ‘wet’ age-related macular degeneration (nAMD), and RHONE-X (NCT04432831), an extension study of YOSEMITE (NCT03622580) and RHINE (NCT03622593) evaluating the long-term safety and tolerability of Vabysmo in diabetic macular edema (DME).18,19 Roche has also initiated several Phase IV studies, including the ELEVATUM (NCT05224102) study of Vabysmo in underrepresented patient populations with DME, the SALWEEN study of Vabysmo in a subpopulation of nAMD highly prevalent in Asia, and the POYANG (NCT06176352) study of Vabysmo in adult treatment-naive patients with choroidal neovascularisation secondary to pathologic myopia.20-22 Roche has also initiated the VOYAGER (NCT05476926) study, a global real-world data collection platform, and supports several other independent studies to further understand retinal conditions with a high unmet need.23 About Vabysmo® (faricimab)Vabysmo is the first bispecific antibody approved for the eye. It targets and inhibits two signalling pathways linked to a number of vision-threatening retinal conditions by neutralising angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A contribute to vision loss by destabilising blood vessels, causing new leaky blood vessels to form and increasing inflammation. By blocking pathways involving Ang-2 and VEGF-A, Vabysmo is designed to stabilise blood vessels.24 Vabysmo is approved in more than 95 countries around the world, including the United States, Japan, the United Kingdom and the European Union for people living with neovascular or ‘wet’ age-related macular degeneration and diabetic macular edema and in several countries, including the US and Japan, for RVO.4,6-9 Review by other regulatory authorities is ongoing. About Roche in ophthalmologyRoche is focused on saving people’s eyesight from the leading causes of vision loss through pioneering therapies. Through our innovation in the scientific discovery of new potential drug targets, personalised healthcare, molecular engineering, biomarkers and continuous drug delivery, we strive to design the right therapies for the right patients. We have the broadest retina pipeline in ophthalmology, which is led by science and informed by insights from people with eye diseases. Our pipeline includes gene therapies and treatments across multiple vision-threatening conditions, including diabetic eye diseases, geographic atrophy and autoimmune conditions, such as thyroid eye disease and uveitic macular edema. Applying our extensive experience, we have already brought breakthrough ophthalmic treatments to people living with vision loss. Susvimo® (previously called Port Delivery System with ranibizumab) 100 mg/mL for intravitreal use via ocular implant was approved by the U.S. Food and Drug Administration in 2021.25 Vabysmo is approved around the world for people living with neovascular or ‘wet’ age-related macular degeneration and diabetic macular edema, and in several countries, including the US and Japan for macular edema following retinal vein occlusion. 4,6-9 Lucentis® (ranibizumab injection)* was the first treatment approved to improve vision in people with certain retinal conditions.5 About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. *Lucentis® (ranibizumab injection) was developed by Genentech, a member of the Roche Group. Genentech retains commercial rights in the United States and Novartis has exclusive commercial rights for the rest of the world. All trademarks used or mentioned in this release are protected by law.References[1] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with macular edema secondary to branch retinal vein occlusion (RVO) (BALATON) [Internet; cited June 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04740905.[2] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with macular edema secondary to central retinal or hemiretinal vein occlusion (COMINO) [Internet; cited June 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04740931. [3] Ghanchi, et al. Efficacy, safety, and durability of faricimab in macular edema due to RVO: 72-week results from the Phase III BALATON and COMINO trials. Poster presented at: ARVO Annual Meeting, May, 5-9 2024, Seattle WA, US. Poster #A0388.[4] U.S. Food and Drug Administration (FDA). Highlights of prescribing information, aflibercept 2 mg. 2022. [Internet; cited June 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125387s076lbl.pdf.[5] FDA. Highlights of prescribing information, Lucentis. 2014. [Internet; cited June 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125156s0069s0076lbl.pdf.[6] FDA. Highlights of prescribing information, Vabysmo. 2022. [Internet; cited June 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761235s003lbl.pdf.[7] FDA approves Genentech’s Vabysmo for the treatment of RVO [Internet; cited June 2024]. Available from: https://www.gene.com/media/press-releases/15009/2023-10-26/fda-approves-genentechs-vabysmo-for-the-treatment-of-RVO. [8] Chugai obtains regulatory approval for Vabysmo, the only bispecific antibody in the ophthalmology field, for additional indication of macular edema associated with RVO. [Internet; cited June 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20240326160000_1054.html. [9] European Medicines Agency. Summary of product characteristics, Vabysmo, 2022 [Internet; cited June 2024]. Available from: https://www.ema.europa.eu/en/documents/product-information/vabysmo-epar-product-information_en.pdf. [10] Chugai obtains regulatory approval for Vabysmo, the first bispecific antibody in ophthalmology, for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) [Internet; cited January 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20220328160002_909.html. [11] Roche data on file.[12] Song P, et al. Global epidemiology of RVO: a systematic review and meta-analysis of prevalence, incidence and risk factors. J Glob Health. 2019;9:010427. [13] Moorfields Eye Hospital, United Kingdom National Health Service Foundation Trust. RVO [Internet; cited June 2024]. Available from: https://www.moorfields.nhs.uk/condition/retinal-vein-occlusion. [14] Joussen et al. Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data. Eye. 2021;35:1305-1316.[15] Regula JT, et al. Targeting key angiogenic pathways with a bispecific CrossMab optimised for neovascular eye diseases. EMBO Molecular Medicine. 2016;8:1265–88.[16] Schmidt-Erfurth U, et al. Guidelines for the management of retinal vein occlusion by the European society of retina specialists (EURETINA). Ophthalmologica. 2019;242:123-162.[17] Campochiaro P. Molecular pathogenesis of retinal and choroidal vascular diseases. Prog Retin Eye Res. 2015;49:67-81. [18] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with nAMD (AVONELLE-X) [Internet; cited June 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04777201. [19] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with DME (RHONE-X) [Internet; cited June 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04432831. [20] Clinical Trials.gov. A study to investigate faricimab treatment response in treatment-naïve, underrepresented patients with DME (ELEVATUM). [Internet; cited June 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT05224102. [21] APVRS. Design and rationale of the SALWEEN Trial: A Phase IIIb/IV Study of faricimab, a dual angiopoietin-2 and vascular endothelial growth factor-a inhibitor, in patients with polypoidal choroidal vasculopathy. [Internet; cited June 2024]. Available from: https://2022.apvrs.org/abstract/?code=200351. [22] A study to evaluate the efficacy and safety of faricimab in patients with choroidal neovascularisation secondary to pathologic myopia (POYANG). [Internet; cited June 2024]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT06176352. [23] Clinical Trials.gov. A Real-World Study to Gain Clinical Insights Into Roche Ophthalmology Products (VOYAGER). [Internet; cited January 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT05476926. [24] Heier JS, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for nAMD (TENAYA and LUCERNE): two randomised, double-masked, Phase III, non-inferiority trials. The Lancet. 2022;399:729-740.[25] FDA. Highlights of prescribing information, Susvimo. 2021. [Internet; cited June 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761197s000lbl.pdf. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Sileia UrechPhone: +41 79 935 81 48 Nathalie AltermattPhone: +41 79 771 05 25 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262 Yvette PetillonPhone: +41 79 961 92 50 Dr. Rebekka SchnellPhone: +41 79 205 27 03 Roche Investor Relations Dr. Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.com Dr. Sabine BorngräberPhone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.com Dr. Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 28062024_MR_Vabysmo RVO CHMP opinion_en