Lesinurad

近日，恒瑞在2024年欧洲风湿病学大会(EULAR)上，披露了SHR4640片联合非布司他片治疗经非布司他治疗未达标的原发性痛风伴高尿酸血症受试者的降尿酸疗效与安全性研究数据，结果表明：在经非布司他治疗未达标的原发性痛风伴高尿酸血症患者中，加用SHR4640可以较安慰剂显著提高血尿酸达标率，降低血尿酸水平，且安全性可控。 关于最新研究数据 本次披露的是一项多中心、随机、双盲、安慰剂平行对照的II期临床试验，纳入经非布司他治疗后未达标的原发性痛风伴高尿酸血症患者。 研究共设3组，按照随机前非布司他剂量（40mg、60mg、80mg）分层，随机化按1:1:1的比例分至SHR4640 5mg联合非布司他组、SHR4640 10mg联合非布司他组和安慰剂联合非布司他组。共分为筛选期、双盲治疗期和安全随访期三个阶段。 主要终点为双盲治疗期第12周时血清尿酸≤360μmol/L 的受试者比例；次要终点为第12周时血清尿酸≤300μmol/L的受试者比例，各次访视血清尿酸较基线变化的百分比；各次访视血清尿酸较基线的变化值等。 结果显示： 治疗12周sUA达标（≤360μmol/L）的受试者百分比：SHR4640 10 mg+非布司他组为56.9%，SHR4640 5 mg+非布司他为53.1%，均显著优于安慰剂+非布司他组13.7%（P值均＜0.0001，OR值分别为8.7和7.1）。 治疗12周血清尿酸≤300μmol/L的受试者百分比：SHR4640 10 mg+非布司他组为43.1%，SHR4640 5 mg+非布司他为38.8%，明显优于安慰剂+非布司他组9.8%。（P值分别为0.0001和0.0009，OR值分别为7.2和5.8）。 治疗12周血尿酸较基线下降比例和下降绝对值：SHR4640 10mg+非布司他组、SHR4640 5mg+非布司他组均明显优于安慰剂组。 在安全性上，SHR4640+非布司他组整体不良事件发生率与安慰剂+非布司他组相似，整个试验期间，无不良事件导致治疗终止或导致死亡。 关于SHR4640 SHR4640是恒瑞针对特异性表达在肾小管上皮细胞的尿酸盐转运体（URAT1）开发的高选择性小分子抑制剂，可通过选择性抑制URAT1对尿酸的转运，从而抑制尿酸的重吸收、促进尿酸的排泄，达到降低血尿酸浓度的目的。SHR4640是研发进度最快的国产URAT1抑制剂，目前处于III期临床阶段。 FOCUS是一项在国内开展的多中心随机双盲对照Ⅱ期试验，旨在评估SHR4640单药在患有或不患有痛风的高尿酸血症（HUA）受试者的疗效和安全性，主要终点是第5周sUA<=360umol/L受试者比例。 临床数据显示：第5周时达到sUA≤360μmol/L的受试者比例在5mg SHR4640组中为32.5%，在10mg SHR4640组中为72.5%，在苯溴马隆组中为61.5%。与安慰剂组相比，5mg和10mg SHR4640组中第5周达到sUA≤360μmol/L的受试者显着增多；与苯溴马隆组相比，10mg SHR4640组达到目标sUA水平的受试者比例较高（72.5%vs 61.5%）。 关于URAT1抑制剂 尿酸盐转运蛋白（Urate Transporter 1）属于有机阴离子转运蛋白（OAT）家族，是重要的肾脏尿酸盐转运体，主要参与尿酸在肾近曲小管的重吸收。URAT1 是治疗慢性痛风的一个重要靶点，URAT1抑制剂可通过抑制URAT1 蛋白活性进而抑制尿酸的重吸收，从而促进尿酸排出并降低血尿酸水平。 URAT1 抑制剂作用机制示意图 目前，在全球范围内获批使用的URAT1 抑制剂主要有苯溴马隆、丙磺舒、雷西纳德和多替诺雷（dotinurad）。在中国市场，目前已上市的URAT1 抑制剂仅有苯溴马隆及丙磺舒；今年1月，卫材多替诺雷dotinurad的上市申请（NDA）已获CDE受理。 然而，苯溴马隆在欧洲因其有引起爆发性肝坏死案例而被退市；在美国市场未批准上市；而在中国市场，苯溴马隆仍然作为慢性痛风的一线治疗用药，建议患者在使用过程中密切检测肝功能。雷西纳德肾毒性机制尚不明确，可能与结构和代谢产物相关。患者急需长期用药安全性好的药物。 据不完全统计，目前全球共有超40余种URAT1药物，将处于在研阶段的管线药物统计如下： 国内有多家企业布局了URAT1抑制剂等痛风治疗药物，除恒瑞外，信诺维、新元素医药、璎黎药业、一品红、海创、益方、珊顿医药、通化东宝、康缘药业、复创医药、正大清江等均在该领域进行布局。 关于痛风 随着经济发展，人民生活水平提高，摄入高糖、高脂肪食物以及高嘌呤食物明显增加，中国高尿酸血症、痛风患病人数呈增加趋势。高尿酸血症已成为继糖尿病、高血压、高血脂症后的“第四高”，痛风已成为仅次于糖尿病的第二大代谢类疾病。 根据弗若斯特沙利文分析，全球痛风患病人数从2016年的1.7亿人增至2020年的2.1 亿人，复合年增长率为5.8%。预计到2025年全球痛风人数将达到2.7亿人，并于2030年达到3.3亿人，期间复合年增长率分别为5.0%和3.7%。 据《中国高尿酸血症与痛风诊疗指南（2019）》及国家统计局第六次人口普查数据显示，中国高尿酸血症的总体患病率为13.3%，患病人数约为1.77 亿，痛风总体发病率为1.1%，患病人数约为1,466 万。考虑到中国未来的人口增长趋势和痛风患病率的升高，预计中国的痛风患病人数会在2025年达到4500万人，在2030年达到5200万人。 在治疗上，急性期痛风以抗炎症药物为一线治疗；如NSAIDs、秋水仙碱，被作为急性痛风期的首选药物。复发/慢性痛风一线治疗应用降尿酸药物，主要有XO抑制剂、促肾脏尿酸排泄药物两大类：黄嘌呤氧化酶（XO）抑制剂，如别嘌醇、非布司他等；促肾脏尿酸排泄药物，如苯溴马隆、丙磺舒等。二线治疗推荐促进尿酸分解药物（普瑞凯希等）或IL-1拮抗剂。 中美高尿酸血症及痛风的治疗指南异同 截止2023年12月，全球范围内临床阶段后的高尿酸血症及痛风性关节炎药物共有147个，已上市43个（其中18款适应症为高尿酸血症且其中4款为复方），申请上市1个，III期临床13个，II/III期临床7个，II期临床21个。URAT1是研发热度最高的抗痛风药物靶点。 根据弗若斯特沙利文数据显示，全球痛风药物市场规模从2016年的28亿美元增长至2019年的32亿美元。受疫情影响，2020年全球痛风药物市场规模减少至26亿美元，换算成人民币亦为百亿赛道。预计将在2025年增长至39亿美元，其中2023-2025年的年复合增长率估算为9.1%。 据数据显示，2020年中国抗痛风药市场规模超过30亿元，然而受集采影响，2021年市场规模下滑至20亿元，其中公立医疗机构终端市场规模下降幅度最大，同比下降40%，而中国网上药店终端同比增长近30%。 参考资料 1、公司官网 2、平安证券、国投证券、西南证券、东吴证券 点击下方“药渡“，关注更多精彩内容 免责声明 “药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。 微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！

Industry leader Barry Quart, Pharm.D. appointed as Chief Executive Officer succeeding Zheng Wei, Ph.D., who will remain on the Board of Directors and serve as an advisor to assist with the transitionExperienced life science executive David Szekeres appointed as PresidentKleanthis G. Xanthopoulos, Ph.D. appointed as Chair of the Board of Directors SAN DIEGO, CA and TAICANG, China, June 12, 2024 (GLOBE NEWSWIRE) -- Connect Biopharma Holdings Limited (Nasdaq: CNTB) (Connect or the Company), a U.S.-headquartered, global clinical-stage biopharmaceutical company dedicated to improving the lives of patients with chronic inflammatory diseases through the development of therapies derived from T cell-driven research, announced today the appointments of Barry Quart, Pharm.D., as Chief Executive Officer (CEO) and Director, David Szekeres as President, and Kleanthis G. Xanthopoulos, Ph.D., as the new Chair of the Board of Directors (Board). Dr. Xanthopoulos, currently the lead independent member of the Board since 2022, has been appointed Chair of the Board. Dr. Xanthopoulos succeeds Wubin (Bill) Pan, Ph.D., M.B.A., who will remain on the Board and serve as an advisor to the Company during the transition. “On behalf of the board and the Connect team I would like to thank Drs. Zheng Wei and Wubin (Bill) Pan, who co-founded Connect with the vision to bring next-generation therapeutics to patients with inflammatory diseases and improve their lives. We are grateful for their contributions and unwavering commitment to the Connect mission by building an outstanding organization with Phase 3-ready programs and a robust pipeline,” said Kleanthis G. Xanthopoulos, Ph.D., Chair of the Board of Directors of Connect. “The highly differentiated data generated from positive readouts in both asthma and atopic dermatitis for the lead asset, rademikibart, establishes Connect now as a U.S.-driven late-stage company entering its pre-commercial phase. I am thrilled to welcome the new leadership team with such an impressive track record and eager to leverage Barry’s and David’s operational expertise and wealth of experience to unlock the maximum potential/value of rademikibart and the rest of the pipeline.” "Founding and leading Connect with Bill and working with many talented colleagues who are passionate about discovery and development of life-changing medicines in the past 12 years has been a true honor and privilege," said Dr. Zheng Wei. "As Connect evolved to focus on advancing rademikibart, Bill and I look forward to supporting Barry and David as Connect enters an exciting new phase." Dr. Barry Quart, the Company’s newly appointed CEO, brings over 30 years of extensive experience serving in leadership positions in biotechnology and pharmaceutical companies and developing innovative pharmaceutical products. He has personally led several early-stage biotech companies through late-stage clinical development and regulatory strategy, highlighted by nine U.S. Food and Drug Administration (FDA) approved drugs. “I am honored to assume the CEO role for Connect and to join the Board. I am incredibly excited about the potential of the Company going forward with rademikibart, which I believe to be a best-in-class competitor to dupilumab,” said Barry Quart, Pharm.D., CEO and Director of Connect. “With the multiple innovative therapies in our pipeline, a cash runway into at least 2026, and an expanded management team with proven experience in the U.S., I believe we have all the elements in place to achieve significant shareholder returns in the future.” Dr. Quart was most recently CEO at Heron Therapeutics. He first served as CEO and Director starting in 2012, transitioned to President and CEO in 2019 and was named Chair of the Board in October 2020. At Heron, Dr. Quart oversaw the development and approval of four drugs: two drugs for CINV (CINVANTI® and SUSTOL®) and two acute care drugs (ZYNRELEF® and APONVIE®). Prior to Heron, Dr. Quart co-founded Ardea Biosciences, Inc. in 2006 and served as its President and Chief Executive Officer and Director from its inception through its acquisition by AstraZeneca PLC in 2012. At Ardea, Dr. Quart invented and oversaw the development of a drug for gout (ZURAMPIC®), as well as the design and development of a series of MEK inhibitors for cancer that were licensed to Bayer AG. Dr. Quart currently serves on the Board of Directors of Kiniksa Pharmaceuticals. He is an inventor on 18 U.S. patents and an author on 75 publications and abstracts. Dr. Quart received his Pharm.D. from the University of California, San Francisco. David Szekeres is an experienced life science executive with a proven track record of creating value with deep operational, commercial, corporate development/strategy, and legal expertise. Mr. Szekeres was most recently Executive Vice President and Chief Operating Officer of Heron Therapeutics. Prior to Heron, he was the Chief Business Officer and General Counsel of Regulus Therapeutics, a clinical-stage biotech company focused on RNA therapeutics and the Head of Mergers & Acquisitions at Life Technologies Corporation. Mr. Szekeres also holds positions as the Chair of the Board of GRI Bio, Inc. (Nasdaq: GRI) and is a member of the Board of Directors of CureMatch, Colossal Biosciences, and the Sanford Burnham Prebys Medical Discovery Institute. He received his J.D. from Duke University School of Law and earned his B.A. at the University of California, Irvine. About Connect Biopharma Holdings Limited Connect Biopharma is a global, clinical-stage biopharmaceutical company applying its expertise in T cell biology and deep knowledge of the drug discovery industry to develop innovative therapies to treat chronic inflammatory diseases with the goal of improving the lives of millions of those affected around the world. The Company is building a rich pipeline of proprietary small molecules and antibodies, using functional T cell assays, to screen and discover potent product candidates against validated immune targets. The Company’s lead product candidate, rademikibart (formerly known as CBP-201), is an antibody designed to target interleukin-4 receptor alpha (IL-4Rα) in development for the treatment of atopic dermatitis and asthma. The Company’s second product candidate, icanbelimod (formerly known as CBP-307), is a modulator of S1P1 T cell receptors and is in development for the treatment of ulcerative colitis (UC). For more information, please visit: https://www.connectbiopharm.com/ Forward-Looking Statements Connect Biopharma cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “may”, “could”, “will”, “would”, “should”, “expect”, “plan”, “anticipate”, “believe”, “estimate”, “intend”, “predict”, “seek”, “contemplate”, “look forward”, “potential”, “continue” or “project” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include the Company’s plans to advance the development of its product candidates, the timing of achieving any development, regulatory or commercial milestones or reporting data or whether such milestones or data will be achieved or generated, including whether any new drug application will be submitted or accepted and the timing thereof, and the potential of such product candidates, including to achieve any benefit, improvement, differentiation, trend or profile or any product approval or be effective, and the sufficiency of the Company’s cash and investments to support planned operations. The inclusion of forward-looking statements should not be regarded as a representation by Connect Biopharma that any of its plans will be achieved. Actual data may differ materially from those set forth in this release due to the risks and uncertainties inherent in the Company’s business and other risks described in the Company’s filings with the Securities and Exchange Commission (SEC), including the Company’s Annual Report on Form 20-F filed with the SEC on April 16, 2024, and its other reports. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Connect Biopharma undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included in Connect Biopharma’s filings with the SEC which are available from the SEC’s website (www.sec.gov) and on Connect Biopharma’s website (www.connectbiopharm.com) under the heading “Investors.” All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995. INVESTOR CONTACT:Tim McCarthyLifeSci Advisorstim@lifesciadvisors.com