Urokinase (Techpool Bio-Pharma)

精彩内容近日，抗血栓药市场再掀波澜，湖南恒生制药的替格瑞洛片、江苏诺泰澳赛诺生物的注射用比伐芦定、华夏生生药业的盐酸替罗非班氯化钠注射液、陕西博森生物制药的阿加曲班注射液同日获批。米内网数据显示，近年中国公立医疗机构终端抗血栓形成药市场规模均超过300亿元，2022年同比有所下滑。产品TOP10中硫酸氢氯吡格雷片稳居“一哥”宝座，达肝素钠注射液和注射用尿激酶首次跻身前十；品牌TOP10中外资企业占据前五席位，独家品种吲哚布芬片大涨65%。目前，有26个品种过评，扬子江、正大制药、石药领跑，肝素类产品首进国采。此外，科伦、海思科、恒瑞等猛攻1类新药。抗血栓药TOP10洗牌！“一哥”止跌，肝素类产品首进国采近年中国公立医疗机构终端抗血栓形成药销售情况（单位：亿元）来源：米内网中国公立医疗机构药品终端竞争格局米内网数据显示，近年中国城市公立医院、县级公立医院、城市社区中心及乡镇卫生院（简称中国公立医疗机构）终端抗血栓形成药市场规模均超过300亿元，2022年同比有所下滑。从细分市场来看，城市公立医院的市场份额下滑，而县级公立医院、城市社区中心及乡镇卫生院均有上涨。从厂家格局来看，赛诺菲、拜耳、河北常山生化药业位居前三，杭州中美华东制药凭借超过60%的增速晋身前十，同时也是TOP20中增速最快的厂家。从治疗小类来看，非肝素类的抗血小板凝集药、肝素类是两大主力，合计市场份额占比超过70%。2022年中国公立医疗机构终端抗血栓形成药产品TOP10来源：米内网中国公立医疗机构药品终端竞争格局产品TOP10销售额均超10亿元，硫酸氢氯吡格雷片、阿司匹林肠溶片、依诺肝素钠注射液位居前三；从增速来看，达肝素钠注射液增速最快，超过30%，硫酸氢氯吡格雷片和注射用尿激酶均超过10%，达肝素钠注射液和注射用尿激酶首次跻身前十。2022年中国公立医疗机构终端抗血栓形成药品牌TOP10来源：米内网中国公立医疗机构药品终端竞争格局品牌TOP10中，外资品牌占据前五席位，仅有赛诺菲的硫酸氢氯吡格雷片为正增长；国产品牌中杭州中美华东制药的独家品种吲哚布芬片增速最快，超过60%。从数量来看，赛诺菲和拜耳各有2个品牌上榜。截至目前，抗血栓形成药已有13个品种被纳入集采，从剂型来看，8个注射剂，4个片剂，1个胶囊剂。其中，注射用比伐芦定（第四批）、利伐沙班片（第五批）下滑幅度最大，均超过50%。值得一提的是，在产品TOP10中，集采品种占据4个席位，硫酸氢氯吡格雷片多年来稳居“一哥”宝座，2022年止跌回升；肝素类产品（依诺肝素钠注射液、那屈肝素钙注射液）首次纳入集采。近年中国公立医疗机构终端硫酸氢氯吡格雷片等3个产品市场份额情况来源：米内网中国公立医疗机构药品终端竞争格局硫酸氢氯吡格雷片是抗血栓形成药市场的明星产品，用于预防和治疗因血小板高聚集状态引起的心、脑及其它动脉的循环障碍疾病。该产品在中国公立医疗机构终端销售峰值曾超过100亿元，受集采影响，2020年下滑超过50%，2021年跌幅收窄，下滑3.11%，2022年同比增长超过10%，赛诺菲、乐普药业、深圳信立泰药业的市场份额位居前三。依诺肝素钠注射液用于预防静脉血栓栓塞性疾病（预防静脉内血栓形成），特别是与骨科或普外手术有关的血栓形成等。近年来在中国公立医疗机构终端依诺肝素钠注射液市场规模均超过20亿元，2022年同比略有下滑，其中，赛诺菲市场份额最大，深圳天道医药、南京健友生化制药、杭州九源基因市场份额均超10%。该产品有13家企业拥有生产批文，10家过评，苏州二叶制药、山东新时代药业、天津红日药业等9家企业集采中标。那屈肝素钙注射液用于治疗急性深静脉血栓，预防急性肾功能衰竭或慢性肾功能不全者进行血液透析和血液过滤期间体外循环系统中的凝血等。2022年中国公立医疗机构终端那屈肝素钙注射液销售额超过10亿元，Aspen、南京健友生化制药、河北常山生化药业合计市场份额近90%。该产品有9家企业拥有生产批文，7家过评，东诚药业、兆科药业、南京健友生化制药等4家集采中标。26个品种过评！扬子江、正大、石药领跑，8个独家过评亮眼抗血栓形成药过评情况来源：米内网中国申报进度（MED）数据库目前，抗血栓形成药有26个品种（299个品规）过评，其中，利伐沙班片最火，过评企业数达40家，替格瑞洛片和阿哌沙班片分别有31家、30家，硫酸氢氯吡格雷片、阿加曲班注射液、盐酸替罗非班氯化钠注射液、依诺肝素钠注射液均有10家及以上企业过评。8个品种是独家过评，分别是石药集团欧意药业的双嘧达莫片、广州一品红制药的注射用奥扎格雷钠、北京泰德制药的贝前列素钠片、浙江北生药业汉生制药的奥扎格雷钠注射液、海南先声药业的甲苯磺酸艾多沙班片、乐普药业的硫酸氢氯吡格雷阿司匹林片、贵州景峰注射剂的盐酸替罗非班注射用浓溶液、烟台东诚北方制药的注射用那屈肝素钙。已过评抗血栓形成药5个及以上的企业（以集团计）从企业过评品种数量来看，扬子江药业、正大制药、石药控股领跑过评榜，各有7个；乐普医疗和复星医药各有6个，齐鲁制药、鲁南制药、上海医药、南京健友生化制药各有5个。1类新药大爆发！百奥泰、施贝康冲刺，科伦、海思科……发力抗血栓形成药1类新药报产在审情况来源：米内网中国申报进度（MED）数据库截至目前，抗血栓形成药有28个品种（142个受理号）报产在审，其中，有2个1类新药。sbk002片用于急性冠状动脉综合征、动脉粥样硬化、缺血性脑卒中、血栓形成等，该产品是成都施贝康生物首个报产获受理的化学1类新药。在此之前，百奥泰的1类新药巴替非班注射液已报产在审，该产品是一种肽类的β3整合素受体抑制剂，用于PCI围术期抗血栓，有望在2023年迎来获批。部分获批临床的抗血栓形成药1类新药情况来源：米内网中国申报进度（MED）数据库2021年至今，抗血栓形成药有近20个1类新药获批临床，涉及四川科伦博泰生物、海思科医药集团、上海恒瑞医药|江苏恒瑞医药、深圳信立泰药业等多家企业。四川科伦博泰生物的SKB336注射液用于预防和治疗血栓栓塞性疾病，是一款靶向FXIa/FXI因子的人源化创新单克隆抗体，目前I期健康受试者研究已完成入组，按照计划开展后续工作。海思科医药集团的注射用HSK36273主要用于血液透析及术中患者的全身抗凝，其主要成分HSK36273是公司在2019年由美国公司eXIthera引进，该药为高选择XIa因子抑制剂，目前国内Ⅱ期临床顺利推进中。公司表示，如该产品获批将进一步丰富产品管线，提升公司竞争力。资料来源：公司公告、米内网数据库注：米内网《中国公立医疗机构终端竞争格局》，统计范围是：中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院，不含民营医院、私人诊所、村卫生室；上述销售额以产品在终端的平均零售价计算。如有疏漏，欢迎指正！本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

Extended Phase 1 data reinforce the potential of NTLA-2002 to be a functional cure for people living with hereditary angioedema (HAE)Across all patients (n=10), a single dose of NTLA-2002 led to a 95% mean reduction in monthly HAE attack rate through the latest follow-upAll patients who achieved greater than 60% plasma kallikrein reduction (n=9) remain completely attack free following the 16-week primary observation period through the latest follow-up; longest attack-free interval is 13.0 months and ongoingAll patients who discontinued concomitant long-term HAE prophylaxis treatment after NTLA-2002 administration (n=6) have reported no HAE attacks since discontinuation through the latest follow-upNTLA-2002 has been well tolerated at all dose levelsIntellia to host investor webcast on Monday, June 12, at 8 a.m. ET CAMBRIDGE, Mass., June 11, 2023 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative therapeutics leveraging CRISPR-based technologies, today announced updated interim results from the Phase 1 portion of the ongoing Phase 1/2 study of NTLA-2002. NTLA-2002 is an in vivo, systemically administered CRISPR candidate being developed as a single-dose treatment for hereditary angioedema (HAE). The data, with a cut-off date of February 17, 2023, were shared in a late-breaking presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2023, being held June 9-11 in Hamburg, Germany, and virtually. “After a single dose of our investigational CRISPR-based therapy, patients living with hereditary angioedema experienced durable elimination of their attacks. We are thrilled to see that the earliest-dosed patients are attack free for approximately a year or longer, with NTLA-2002 demonstrating a very favorable safety profile. These remarkable attack rate reductions have been consistent, even in patients with the most severe symptoms,” said Intellia President and Chief Executive Officer John Leonard, M.D. “While early, these unprecedented interim data from the Phase 1 study continue to reinforce our belief that NTLA-2002 could be a potential functional cure for people with hereditary angioedema. In addition, these data strengthen our view that NTLA-2002 could address the significant treatment burden that exists, despite currently available, chronically administered therapies.” In the Phase 1 portion of the study, single doses of 25 mg (n=3), 50 mg (n=4) and 75 mg (n=3) of NTLA-2002 were administered via intravenous infusion, and HAE attacks and plasma kallikrein protein levels were measured for each patient. The first analysis of HAE attack rates occurred at the end of the pre-specified 16-week primary observation period. HAE attacks and plasma kallikrein protein levels will continue to be assessed through the end of the study. HAE Attack Rate Reduction Monthly HAE Attack Rate Reduction from Baseline1 25 mg (n=3)50 mg (n=4)75 mg (n=3)All Patients (N=10)Week 1-1691%97%80%89%Week 5-1689%100%87%92%On-study period295%98%93%95% 1 Investigator confirmed HAE attack rate. 2 On-study period is defined as the time from the dosing of NTLA-2002 through the last assessment of HAE attacks as of the data cut-off date. Across all patients, a 95% mean reduction in monthly attack rate was observed after a single dose of NTLA-2002 through the latest follow-up. The median duration of follow-up was 9.0 months (range of 5.6 - 14.1 months). At each dose level tested, a robust level of HAE attack rate reduction was achieved. Importantly, the elimination of HAE attacks has been sustained and long lasting. The first three patients dosed in the study with the longest follow-up to date have experienced attack-free durations of approximately one year or longer. Additionally, the reduction in HAE attacks has been persistent in patients with the most severe HAE symptoms. The three patients with the highest historic monthly HAE attack rates at the start of the study (16.8, 14.0 and 4.4 attacks per month, respectively) all became attack free by the end of the 16-week primary observation period and remained free of attacks through the latest follow-up. The longest attack-free duration in this patient group is 11.5 months and ongoing. All nine patients who achieved greater than 60% plasma kallikrein reduction, the target level expected to yield a highly meaningful clinical response, remain completely attack free since the 16-week observation period. There was one patient in the lowest 25 mg dose cohort who did not achieve the targeted 60% minimum kallikrein reduction post-NTLA-2002 administration. Following 12.3 months of being attack free, this patient reported a single, mild HAE attack after experiencing minor hand swelling precipitated by a sports injury. The event did not require any medical intervention or acute therapy. The patient has not experienced any subsequent HAE attacks following this event. Six of the 10 patients were receiving long-term HAE prophylaxis medications prior to the administration of NTLA-2002. Subsequently, they were permitted to withdraw their medication at the investigator’s discretion. All six patients have discontinued their prophylactic therapy and have not experienced any subsequent HAE attacks. Plasma Kallikrein ReductionAs previously reported, administration of NTLA-2002 led to dose-dependent, robust and durable reductions in plasma kallikrein. These deep reductions in plasma kallikrein continue to be sustained through the latest follow-up, as described below, which ranged from 24 to 48 weeks across all three dose cohorts. Dose LevelPlasma Kallikrein Level Mean % Reduction from Baseline at Latest Follow-up25 mg (n=3)67% (Week 48)50 mg (n=4)84% (Week 24)75 mg (n=3)95% (Week 32) Safety At all three dose levels, NTLA-2002 has been well tolerated, and the majority of adverse events were mild in severity. Consistent with previously reported results, the most frequent adverse events were infusion-related reactions and fatigue, which were mostly Grade 1 and resolved within two days. There have been no dose-limiting toxicities, no serious adverse events and no adverse events of Grade 3 or higher observed to date. No clinically significant laboratory abnormalities were observed in any patient. As previously announced, the Phase 2 portion of this Phase 1/2 clinical trial of NTLA-2002 has begun dosing patients, and Intellia expects to complete enrollment in the second half of this year. Intellia Therapeutics Investor Webcast InformationIntellia will host a live webcast, Monday, June 12, 2023, at 8:00 a.m. ET to review the new data. Joining the Intellia management team will be Dr. Timothy J. Craig, tenured professor of Medicine, Pediatrics and Biomedical Sciences at Penn State University, to provide an overview of the current treatment landscape and unmet medical need for people living with HAE. To join the webcast, please visit this link, or the Events and Presentations page of the Investors & Media section of the company’s website at www.intelliatx.com. A replay of the webcast will be available on Intellia’s website for at least 30 days following the call. About the NTLA-2002 Clinical ProgramIntellia’s global Phase 1/2 study is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2002 in adults with Type I or Type II hereditary angioedema (HAE). This includes the measurement of plasma kallikrein protein levels and activity, as well as HAE attack rate. The Phase 1 portion of the study is an open-label, single-ascending dose design used to identify two dose levels of NTLA-2002 for further evaluation in the Phase 2, randomized, placebo-controlled portion of the study. The Phase 1/2 study will identify the dose of NTLA-2002 for use in future studies. Patient screening and dosing in the Phase 2 portion of the study is ongoing. Visit clinicaltrials.gov (NCT05120830) for more details. About NTLA-2002Based on Nobel-prize winning CRISPR/Cas9 technology, NTLA-2002 is the first single-dose investigational treatment being explored in clinical trials for the potential to continuously reduce kallikrein activity and prevent attacks in people living with hereditary angioedema (HAE). NTLA-2002 is a wholly owned investigational CRISPR therapeutic candidate designed to inactivate the kallikrein B1 (KLKB1) gene, which encodes for prekallikrein, the kallikrein precursor protein. NTLA-2002 is Intellia’s second investigational CRISPR therapeutic candidate to be administered systemically, by intravenous infusion, to edit disease-causing genes inside the human body with a single dose of treatment. Intellia’s proprietary non-viral platform deploys lipid nanoparticles to deliver to the liver a two-part genome editing system: guide RNA specific to the disease-causing gene and messenger RNA that encodes the Cas9 enzyme, which together carry out the precision editing. About Hereditary Angioedema Hereditary angioedema (HAE) is a rare, genetic disorder characterized by severe, recurring and unpredictable inflammatory attacks in various organs and tissues of the body, which can be painful, debilitating and life-threatening. It is estimated that one in 50,000 people are affected by HAE, and current treatment options often include life-long therapies, which may require chronic intravenous (IV) or subcutaneous (SC) administration as often as twice per week, or daily oral administration to ensure constant pathway suppression for disease control. Despite chronic administration, breakthrough attacks still occur. Kallikrein inhibition is a clinically validated strategy for the preventive treatment of HAE attacks. About Intellia TherapeuticsIntellia Therapeutics, a leading clinical-stage genome editing company, is developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. To fully realize the transformative potential of CRISPR-based technologies, Intellia is pursuing two primary approaches. The company’s in vivo programs use intravenously administered CRISPR as the therapy, in which proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia’s ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its robust intellectual property portfolio, have enabled the company to take a leadership role in harnessing the full potential of genome editing to create new classes of genetic medicine. Learn more at intelliatx.com. Follow us on Twitter @intelliatx. Forward-Looking Statements This press release contains “forward-looking statements” of Intellia Therapeutics, Inc. (“Intellia” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellia’s beliefs and expectations regarding: the safety, efficacy, success and advancement of its clinical program for NTLA-2002 for the treatment of hereditary angioedema pursuant to its clinical trial applications and investigational new drug application, including the expected completion of enrollment for the Phase 2 portion of the Phase1/2 study for NTLA-2002 this year, the potential for NTLA-2002 to be a functional cure for people living with HAE, and the potential of NTLA-2002 to address the significant treatment burden that exists, despite currently available, chronically administered therapies. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellia’s ability to protect and maintain its intellectual property position; risks related to Intellia’s relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the authorization, initiation, enrollment and conduct of studies and other development requirements for its product candidates, including NTLA-2002; the risk that NTLA-2002 will not be successfully developed and commercialized; and the risk that the results of preclinical studies or clinical studies, such as the clinical study of NTLA-2002, will not be predictive of future results in connection with future studies for the same product candidate or Intellia’s other product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellia’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Intellia’s most recent annual report on Form 10-K and quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law. Intellia Contacts: Investors:Ian KarpSenior Vice President, Investor Relations and Corporate Communications+1-857-449-4175ian.karp@intelliatx.comLina LiSenior Director, Investor Relations and Corporate Communications+1-857-706-1612lina.li@intelliatx.com Media:Matt CrensonTen Bridge Communications+1-917-640-7930media@intelliatx.com TBCIntellia@tenbridgecommunications.com