Human Coagulation Factor IX (Yuanda Shuyang)

点击蓝字关注我们本周，审评审批方面：国内来说，阿斯利康和第一三共联合开发的注射用德曲妥珠单抗在中国获批上市。中国生物制药3类化药利马前列素片获批上市，针对中老年人常见病。国外而言，甘李药业的甘精胰岛素在美国申报上市。研发方面，吉利德三联长效HIV疗法I期研究积极，90%患者实现病毒抑制。交易及投融资方面，康诺亚和乐普生物共同宣布与阿斯利康就CMG901达成全球独家授权协议；上市方面，科伦药业子公司科伦博泰拟赴港上市。       本期盘点包括审评审批、研发、交易及投融资、上市4个板块，统计时间为2.20-2.24，包含25条信息。 审评审批NMPA上市批准1、2月20日，NMPA官网显示，中国生物制药的3类化药利马前列素片（商品名：凯立通）获批上市，用于镇痛和微循环领域治疗。利马前列素片是目前临床唯一在说明书中明确适应症为腰椎管狭窄症治疗的小分子化药，是国内首 个针对腰椎管狭窄症病理机制，兼具改善神经血流微循环障碍和改善神经功能的双重功效的药物，为腰椎管狭窄症全程管理的基础用药。       2、2月20日，NMPA官网显示，苏庇医药的尼替西农胶囊以及口服混悬液获批上市，适应症为结合酪氨酸和苯丙氨酸饮食限制，用于治疗成人和儿科患者（任何年龄阶段）的遗传性酪氨酸血症I型（HT-1）。尼替西农由瑞士Orphan BiovitrumAB公司开发，是一款4-羟苯丙酮酸双氧酶可逆抑制剂。       3、2月20日，NMPA官网显示，艾伯维的乌帕替尼缓释片第4个适应症获批上市，用于治疗对一种或多种肿瘤坏死因子（TNF）抑制剂应答不佳或不耐受或禁忌的中重度活动性溃疡性结肠炎（UC）成人患者。乌帕替尼是艾伯维自主研发的一种JAK1抑制剂，酶活性和细胞试验结果显示，其对JAK1的抑制效力高于JAK2、JAK3和TYK2。       4、2月20日，NMPA官网显示，吉利德的注射用两性霉素B脂质体（商品名：安必速）获批上市，用于治疗侵袭性真菌病。安必速可全面覆盖念珠菌、曲霉、毛霉和隐球菌等多种真菌，其对念珠菌整体应答率更高达90%，且耐药罕见。       5、2月20日，NMPA官网显示，远大蜀阳药业的人凝血因子IX获批上市，本次获批的适应症为：用于预防和治疗人凝血因子IX缺乏症（血友病B）导致的出血。血友病是一种罕见的隐性遗传性出血性疾病，可分为血友病A和血友病B两种类型，均由相应的凝血因子基因突变引起。其中，血友病B由凝血因子Ⅸ缺乏导致。       6、2月24日，NMPA官网显示，阿斯利康和第一三共联合开发的注射用德曲妥珠单抗已正式在中国获批上市。公开资料显示，优赫得(英文商品名：Enhertu，通用名：德曲妥珠单抗)是一款靶向HER2的抗体偶联药物(ADC)，已在海外获批多种适应症。本次为该药首次在中国获批，针对的适应症为：单药适用于治疗既往接受过一种或一种以上抗HER2药物治疗的不可切除或转移性HER2阳性成人乳腺癌患者。  申请7、2月20日，CDE官网显示，上海医药的全资子公司上药信谊合作开发的X842提交上市申请并获受理，拟用于治疗反流性食管炎。X842是新一代钾离子竞争性酸阻断剂（P-CAB）口服药物。上海医药于2021年10月从生诺生物以不超过6.9亿元的交易金额获得了X842在中国区域的独家委托生产和所有适应症的工业销售权。       8、2月20日，CDE官网显示，罗欣药业的1类新药替戈拉生片的新适应症提交上市申请并获受理，推测新适应症为十二指肠溃疡。替戈拉生是国内首 款自研钾离子竞争性酸阻滞剂（P-CAB），2015年10月，罗欣药业与韩国CJHealthCare达成协议，获得替戈拉生中国境内开发、生产及商业化权益。       9、2月22日，CDE官网显示，再鼎医药的舒巴坦钠-度洛巴坦钠（SUL-DUR）提交上市申请并获受理，用于治疗鲍曼不动杆菌（包括多重耐药和耐碳青霉烯类[CRAB]菌株）引起的感染。SUL-DUR是由舒巴坦钠（一种静脉输注的β-内酰胺类抗生素）和度洛巴坦钠（一种新型广谱静脉输注的β-内酰胺酶抑制剂）组合而成。临床批准       10、2月20日，CDE官网显示，辉瑞的1类新药PF-06821497片获批临床，拟开发用于治疗晚期恶性肿瘤，包括小细胞肺癌、去势抵抗性前列腺癌、滤泡性淋巴瘤。PF-06821497是一款在研的EZH2抑制剂，尚未在全球任何国家和地区获批上市。       申请       11、2月21日，CDE官网显示，华东医药全资子公司中美华东与Provention Bio共同递交了1类新药PRV-3279的临床试验申请。这是一款靶向CD32b和CD79b的人源化双特异性抗体，华东医药以最高近1.9亿美元获得其两个临床适应症在大中华区的独家临床开发和商业化权益。优先审评12、2月22日，CDE官网显示，赛诺菲的度普利尤单抗注射液新适应症请拟纳入优先审评，用于治疗成人结节性痒疹。度普利尤单抗是一款抗IL-4/IL-13单抗，是一款领域横跨皮肤科、呼吸科、变态反应用药的生物制剂，目前获批的适应症包括特应性皮炎、哮喘、结节性痒疹、嗜酸性粒细胞性食管炎（用于12岁及以上患者）和慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）等。       13、2月22日，CDE网站显示，联拓生物引进的Mavacamten胶囊拟纳入优先审评，适用于治疗症状性纽约心脏病协会（NYHA）心功能Ⅱ-Ⅲ级的梗阻性肥厚型心肌病（oHCM）成人患者。Mavacamten是一款first-in-class的心肌肌球蛋白抑制剂。FDA上市申请14、2月21日，Alnylam宣布，RNAi疗法patisiran的新适应症提交上市申请并获FDA受理，用于治疗转甲状腺素介导的淀粉样变性心肌病，PDUFA日期为2023年10月8日。转甲状腺素蛋白淀粉样变性是一种由错误折叠的转甲状腺素蛋白（TTR）蛋白引起的快速进展的罕见疾病，这些蛋白以淀粉样纤维的形式积聚在多个组织中，包括神经、心脏和胃肠道。       15、2月21日，Orasis宣布，老花眼滴眼液CSF-1（0.4%毛果芸香碱）提交上市申请并获FDA受理，PDUFA日期为2023年10月22日。CSF-1是一款由低剂量毛果芸香碱（0.4%）和多种载体组成的不含防腐剂的配方眼药水，它是通过调节瞳孔，产生"针孔效应"并增加景深，从而改善近视力。       16、2月23日，甘李药业宣布，甘精胰岛素注射液的生物制品许可申请（BLA）获FDA受理，进入实质审查阶段。甘精胰岛素是一种长效胰岛素类似物，又称基础胰岛素。经过修饰后可在较长时间内提供稳定水平的血浆胰岛素，仅需每天注射一次。临床   批准17、2月20日，人福医药发布公告，称其子公司宜昌人福药业的RFUS144注射液获FDA批准临床试验。2022年7月，该产品已在中国获批临床。RFUS-144注射液临床拟用于治疗疼痛和瘙痒，是一种选择性阿片受体激动剂，国内目前尚无同类型产品上市。       18、2月21日，上海医药发布公告，其全资子公司上药信谊申报的WST01制剂获FDA批准临床试验，即将启动I期临床试验，拟用于体重管理。WST01是一种口服微生态活菌制剂，由上药信谊和上海市内分泌代谢研究所合作研发并共享知识产权。突破性疗法19、2月22日，Moderna/默沙东宣布，二者共同开发的个性化mRNA肿瘤疫苗mRNA-4157/V940联用默沙东PD-1单抗Keytruda作为高危黑色素瘤患者完全切除后的辅助治疗获FDA突破性疗法认定。Moderna的个体化癌症疫苗旨在通过mRNA编码癌症患者肿瘤细胞中因基因突变而产生的新抗原。研发临床状态20、2月22日，礼来在clinicaltrials.gov网站上注册了一项Ⅲb期临床试（TRAILBLAZER-ALZ 6），以评估donanemab不同给药方案对早期阿尔茨海默病（AD）成人淀粉样蛋白相关影像学异常-水肿/积液（ARIA-E）频率和严重程度的影响，并探索可能预测ARIA风险的受试者特征。       21、2月22日，中国药物临床试验登记与信息公示平台显示，礼来启动了一项国际多中心Ⅲ期临床试验（含中国），以评估remternetug皮下注射治疗早期症状性阿尔茨海默病的安全性和有效性。Remternetug是一种抗体新药，靶向一种名为N3pG的淀粉样蛋白亚型。临床数据22、2月22日，吉利德宣布，艾滋病病毒（HIV）衣壳蛋白抑制剂lenacapavir与2种广谱中和抗体（bNAbs）即Teropavimab和Zinlirvimab联用，治疗HIV感染的I期研究数据。研究结果显示，半年给药一次的三药联用疗法在HIV感染患者中显示出了良好的安全性和有效性。交易及投融资23、2月22日，华东医药全资子公司杭州中美华东制药与日本SCOHIAPHARMA联合宣布，二者将就SCO-094及其衍生产品在全球范围内扩大战略合作。SCO-094是一种GLP-1/GIP双靶点激动剂，通过选择性激活GLP-1受体和GIP受体，激动下游通路，产生控糖、减重等生物学效应。       24、2月23日，康诺亚和乐普共同宣布，与阿斯利康就CMG901达成全球独家授权协议。根据许可协议，阿斯利康将负责CMG901的全球研发、生产和商业化。CMG901是首个在中国及美国均取得临床试验申请批准的靶向Claudin 18.2的全新重组人源化单抗ADC药物，正在进行治疗Claudin18.2阳性表达的实体瘤患者的I期临床试验。 上市港交所25、2月22日，科伦药业发布公告，其子公司科伦博泰于2023年2月15日向中国证监会提交的首次公开发行境外上市外资股（H股）并在香港联交所主板上市的申请材料，已于近日取得中国证监会出具的行政许可受理函（受理序号：230240）。中国证监会对科伦博泰提交的关于本次发行上市的申请材料，经审查符合法定形式，决定对该行政许可申请予以受理。智药研习社3月线下研习会报名快来领取您的喜马拉雅VIP会员！来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

HEMGENIX® underscores CSL's promise to deliver life-changing innovations that have the potential to help patients lead full lives MARBURG, Germany, Feb. 20, 2023 /PRNewswire/ -- Global biotechnology leader CSL (ASX: CSL) today announced that the European Commission has granted conditional marketing authorization (CMA) for HEMGENIX® (etranacogene dezaparvovec), the first and only one-time gene therapy for the treatment of severe and moderately severe hemophilia B (congenital Factor IX deficiency) in adults without a history of Factor IX inhibitors. In the ongoing clinical trial, HEMGENIX® reduced the rate of annual bleeds with a single infusion by delivering a functional gene that acts as a blueprint for coagulation Factor IX, a protein important for blood clotting.1 It is the first approved gene therapy for hemophilia B in the European Union (EU) and European Economic Area (EEA). "The approval of HEMGENIX® in Europe is the essence of great science delivering a medicine that we believe can transform the treatment paradigm for both people living with hemophilia B and the healthcare professionals who treat them," said Dr. Bill Mezzanotte, Head of Research & Development and Chief Medical Officer, CSL. "HEMGENIX®, and our partnership with uniQure, underscore CSL's promise to pursue, develop and deliver disruptive innovations when patients can benefit, particularly in disease states we know well like hemophilia B." People living with hemophilia B currently require lifelong treatment of intravenous infusions of Factor IX to maintain sufficient levels, which can have a significant impact on their quality of life and wellbeing.2 According to the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP), there is 'an unmet medical need for new therapeutic approaches that might free patients from the burden of frequent infusions, or episodically at the time of a bleeding event'.3 The European Commission's decision follows the CHMP's positive opinion in December 2022, based on findings from the pivotal HOPE-B trial, the largest gene therapy trial in hemophilia B to date.4,5 These findings showed that hemophilia B patients treated with HEMGENIX® demonstrated stable and durable increases in mean Factor IX activity levels (with a mean Factor IX activity of 36.9%) which led to an adjusted annualized bleed rate (ABR) reduction of 64%.1 Following infusion of HEMGENIX®, 96% of patients discontinued routine Factor IX prophylaxis and mean Factor IX consumption was reduced by 97% at 18 months post-treatment, compared to the lead-in period.1 The HOPE-B study 24-month analysis continued to show a sustained and durable effect of HEMGENIX®.6 In a clinical setting, the treatment is generally well-tolerated with no serious treatment-related adverse events.5 "This approval marks an important step forward in the treatment of hemophilia B, which could be transformative for people who are debilitated by bleeds into their muscles, joints and internal organs, alleviating the burden of lifelong intravenous infusions of Factor IX products," said Professor Wolfgang Miesbach, Head of Coagulation Disorders at the Comprehensive Care Center, University Hospital of Frankfurt. "Data from the HOPE-B study demonstrate the potential of HEMGENIX® to remove the need for routine prophylaxis, by providing durable Factor IX activity, as well as improved bleeding outcomes and quality of life for people with hemophilia B." "At CSL Behring, our promise is simple – to save and improve lives – and we achieve this by living our core values of patient focus, innovation, integrity, collaboration, and superior performance," commented Lutz Bonacker, Senior Vice President and General Manager of Commercial Operations Europe, CSL Behring. "The approval of HEMGENIX® in Europe is a result of that focus and a milestone for the hemophilia B community, and we now need to work to ensure that as many eligible patients across Europe can access this innovative treatment as possible. We are fully committed to working together with payers and other stakeholders to achieve this." The European Commission has the authority to approve medicines for EU Member States, as well as well as in the EEA countries of Iceland, Norway and Liechtenstein. The multi-year clinical development of HEMGENIX® was led by uniQure (Nasdaq: QURE) and sponsorship of the clinical trials transitioned to CSL after it licensed global rights to commercialize the treatment. In the United Kingdom, The Medicines and Healthcare products Regulatory Agency (MHRA) is currently reviewing CSL's submission for HEMGENIX®. HEMGENIX® was approved by the U.S. Food and Drug Administration in November 2022. About Hemophilia B Hemophilia B is a life-threatening rare disease. People with the condition are particularly vulnerable to bleeds in their joints, muscles, and internal organs, leading to pain, swelling, and joint damage. Current treatments for moderate to severe hemophilia B include life-long prophylactic infusions of factor IX to temporarily replace or supplement low levels of the blood-clotting factor. About HEMGENIX® HEMGENIX® is an adeno-associated virus five (AAV5)-based gene therapy given as a one-time treatment for moderately severe to severe hemophilia B patients. HEMGENIX® (also known as CSL222, previously known as AMT-061) uses a specific type of AAV, called AAV5, as its vector. The AAV5 vector carries the naturally occurring Padua gene variant of Factor IX (Factor IX-Padua), which generates Factor IX proteins that are 5x-8x more active than normal. About the Pivotal HOPE-B Trial The pivotal Phase III HOPE-B trial is an ongoing, multinational, open-label, single-arm study to evaluate the safety and efficacy of HEMGENIX®. Fifty-four adult hemophilia B patients classified as having a diagnosis of moderately severe or severe hemophilia B and requiring prophylactic Factor IX replacement therapy were enrolled in a prospective, six-month observational period during which time they continued to use their current standard of care therapy to establish a baseline Annual Bleeding Rate (ABR). After the six-month lead-in period, patients received a single intravenous administration of HEMGENIX® at the 2x10^13 gc/kg dose. Patients with pre-existing neutralizing antibodies (NAbs) to AAV5 were not excluded from the trial. A total of 54 patients received a single dose of HEMGENIX® in the pivotal trial, with 53 patients completing at least 18 months of follow-up. The primary endpoint in the pivotal HOPE-B study was 52-week ABR after achievement of stable Factor IX expression compared with the six-month lead-in period. For this endpoint, ABR was measured from month seven to month 18 after infusion, ensuring the observation period represented a steady-state Factor IX transgene expression. Results from the pivotal HOPE-B study demonstrated that HEMGENIX® produced mean Factor IX activity of 36.9 IU/dL at 18 months post infusion. At 24 months follow-up, Factor IX activity remained stable at 36.7 IU/DL. After the six-month lead-in period post-infusion, the adjusted annualized bleeding rate (ABR) (1.51) for all bleeds was reduced by 64 percent (p=0.0002) and all Factor IX-treated bleeds was reduced by 77 percent (3.65 to 0.83; p<0.0001) over months seven to 18. From day 21 through to months 7 to 24, 52 of 54 (96.3%) treated patients remained free of continuous routine Factor IX prophylaxis. The mean consumption of Factor IX replacement therapy significantly decreased by 248,392.6 IU/year/patient (96.52%; 1-sided p< 0.0001) between month 7 to 24 following treatment with HEMGENIX® compared to standard of care routine Factor IX prophylaxis during the lead-in period. Further analyses showed that there was no clinically meaningful correlation between patient AAV5 NAb levels at baseline and Factor IX activity. No serious adverse reactions were identified. One death resulting from urosepsis and cardiogenic shock in a patient at 65 weeks following dosing was considered unrelated to treatment by investigators and the company sponsor. A serious adverse event of hepatocellular carcinoma was determined to be unrelated to treatment with HEMGENIX® by independent molecular tumor characterization and vector integration analysis. No inhibitors to Factor IX were reported. About CSL CSL Limited (ASX: CSL; USOTC: CSLLY) is a leading global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat hemophilia and immune deficiencies, as well as vaccines to prevent influenza. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses, CSL Behring, CSL Seqirus, and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 30,000 people. Our unique combination of commercial strength, R&D focus, and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on Twitter.com/CSL. For more information visit . Media Contacts Stephanie Fuchs Mobile: +49 151 584 388 60 Email: [email protected] Greg Healy Mobile: +1 610 906 4564 Email: [email protected] In Australia Kim O'Donohue Mobile: +61 449 884 603 Email: [email protected] Jimmy Baker Mobile: +61 450 909 211 Email: [email protected] References SOURCE CSL