Multiple Sclerosis, Primary Progressive

上海 2024年10月29日 /美通社/ -- 第七届中国国际进口博览会（以下简称"进博会"）将于11月5日至10日在上海举办。作为最早向商务部表示支持并参加进博会的跨国企业，罗氏制药将携手罗氏诊断七赴进博之约。今年是罗氏制药在华成立三十周年，作为医疗器械及医药保健展区面积最大的展商之一，罗氏将以"华彩三十，聚氏未来"为主题，于1000平方米的进博展台上全面展示超过30款已上市和即将在华上市的全产品矩阵及创新解决方案，重磅推出3款即将在华获批的全球创新产品——中国首个且唯一PI3Kα抑制剂伊那利塞（Inavolisib）、首个在全球上市的用于B细胞淋巴瘤治疗的CD20/CD3双特异性抗体创新药Lunsumio（Mosunetuzumab）、全球首个也是唯一一个同时获批用于治疗复发型多发性硬化和原发进展型多发性硬化的药物Ocrevus（Ocrelizumab，奥瑞利珠单抗）。罗氏在华未来管线也将首次亮相进博舞台，重点展示慢阻肺领域、全球首创的全人源化抗ST2单克隆抗体Astegolimab。此外，罗氏还将带来多个"进博宝宝"和明星产品——抗流感创新药速福达 ® （玛巴洛沙韦）、全球首个乳腺癌抗HER2双靶皮下复方制剂赫双妥 ® （帕妥珠曲妥珠单抗）、全球首个作用于复发难治淋巴瘤的靶向CD20/CD3的双特异性抗体创新药高罗华 ® （格菲妥单抗）、全球首个眼科注射双特异性抗体罗视佳 ® （法瑞西单抗）以及一款治疗阵发性睡眠性血红蛋白尿症（PNH）的创新药派圣凯 ® （可伐利单抗）。 "进博会不仅是中国坚持高水平对外开放的窗口，更是汇聚全球创新的绝佳舞台。罗氏连续七年‘打卡'进博会，受益于进博会强大的溢出效应，并借助新药审评审批制度和相关政策东风，罗氏展出的多款全球创新产品都搭上了‘进博快车'，从‘展品'变为‘商品'，充分彰显了‘中国速度'，更快惠及更多的中国患者。今年，罗氏再次带来超过30款已上市和即将在华上市的全产品矩阵及创新解决方案，重磅推出3款即将在华上市的全球创新产品，覆盖乳腺癌、血液肿瘤和神经科学领域。进博会不仅为罗氏展示创新成果提供了绝佳平台，也为我们连接生态圈合作伙伴搭建了共创机遇、共享未来的桥梁。今年喜逢罗氏制药在华成立三十周年，站在而立之年的新起点，我们期待依托进博会继续拥抱开放、深化合作，与中国医疗健康事业同频共振，携手书写华彩篇章。未来，我们将不断加大在华投资，持续深耕中国市场，全面强化端到端的完整医药价值产业链，升级本地化生产布局和投资，让罗氏的创新药惠及更多患者。"罗氏制药中国总裁边欣女士表示。 携三款即将在华上市的全球产品及未来管线亮相进博舞台 今年是罗氏制药在华成立三十周年，在罗氏进博展台上，节节攀升的"创新力量"生动诠释了罗氏三十年来不断凝聚多方创新力量、惠及更多患者，谱写健康未来的新蓝图。进博会历来是全球新品和前沿科技汇聚的首发地。今年，罗氏再次带来超过30款已上市和即将在华上市的全产品矩阵及未来管线。罗氏制药全球刚刚发布了2030愿景——"以20款颠覆性药物，应对社会疾病重负"，聚焦抗肿瘤、神经科学、眼科、免疫、心血管及代谢五大重点疾病领域。今年，罗氏带来其中3款即将在华上市的全球创新产品，点亮进博舞台。在乳腺癌领域，罗氏引领乳腺癌走向精准治愈。中国首个且唯一PI3Kα抑制剂伊那利塞（Inavolisib）将迎来进博"首展首秀"，这是罗氏旗下一款具有同类最佳潜力的创新口服靶向治疗药物，中国领先美国FDA两个月获得突破性疗法和优先审评双认定。PIK3CA突变指示预后不良，在中国乳腺癌人群中，该突变率高达46%，高于非亚裔人群。伊那利塞能从源头阻断肿瘤突变通路，PFS（无进展生存期）超双倍获益，有望为HR阳性、HER2阴性的局部晚期或转移性乳腺癌成人患者带来更优的治疗选择。作为血液肿瘤的领导者，罗氏拥有丰富的产品管线。此次，罗氏将带来首个在全球上市的用于B细胞淋巴瘤治疗的CD20/CD3双特异性抗体创新药Lunsumio（Mosunetuzumab），其将为复发滤泡性淋巴瘤患者提供一种有效的、易于获得的、以及固定周期给药的全新选择。罗氏长期扎根神经科学领域，此次带来了全球首个也是唯一一个同时获批用于治疗复发型多发性硬化和原发进展型多发性硬化的药物Ocrevus（Ocrelizumab，奥瑞利珠单抗）。此外，罗氏在华未来管线也将首次亮相进博舞台，重点展示不断加码布局的如慢阻肺等疾病领域的最新研发成果和未来战略方向，包括全球首创的全人源化抗ST2单克隆抗体Astegolimab，其独特的作用机制能带来更广泛的患者获益，有望成为首款治疗慢性阻塞性肺疾病的ST2单抗。 除了展示全球创新产品，罗氏还将带来10多场重磅发布会，覆盖数字化医疗、提升创新疗法可及性等多个领域的跨界合作，云集突破性成果，携手多方合作伙伴，合力打造医疗创新生态圈。此外，结合前沿的人工智能与数字化等"黑科技"，罗氏将赛博双臂咖啡机、早肺医学装置等带到了本届进博会，并设置抗流感互动体验以及眼底病筛查体验等多个沉浸式创意互动区，为观众打造集科技性、趣味性和未来感为一体的疾病科普新体验。 见证溢出效应持续放大，罗氏"展品"加速变"商品" 七年来，受益于进博会强大的溢出效应和新药审评审批加速的政策东风，罗氏旗下多款产品和解决方案从"展品"加速变成"商品"，惠及更多中国患者。本届进博会，罗氏将带来多个"进博宝宝"和明星产品——抗流感创新药速福达 ® （玛巴洛沙韦）、全球首个乳腺癌抗HER2双靶皮下复方制剂赫双妥 ® （帕妥珠曲妥珠单抗）、全球首个作用于复发难治淋巴瘤的靶向CD20/CD3的双特异性抗体创新药高罗华 ® （格菲妥单抗）、全球首个眼科注射双特异性抗体罗视佳 ® （法瑞西单抗）以及一款治疗阵发性睡眠性血红蛋白尿症（PNH）的创新药派圣凯 ® （可伐利单抗）。近2年，罗氏就有16款创新药及新适应症在华获批上市。 其中，罗氏多款历届"进博宝宝"不断推陈出新，在本届进博舞台续写精彩的"进博故事"。罗氏"进博明星宝宝"速福达 ® （玛巴洛沙韦）在本届进博会再度闪耀亮相。其在第三届进博会期间被纳入境外临床急需用药名单，次年就在华获批上市。目前，这款产品不仅实现了医保覆盖，支持互联网医院在线购药，并且获批了儿童适应症和干混悬剂。根据最新发布的III期临床试验CENTERSTONE研究结果显示，流感患者单次口服抗流感创新药速福达 ® 后，可减少向其家庭成员传播流感病毒的可能性。更值得一提的是，速福达 ® 在今年已成功实现本地化生产，这将大幅缩短其全球供应链周期，更好满足中国患者在流感高发季节的需求，助力中国公共卫生事业发展。此外，罗氏去年诞生的进博宝宝高罗华 ® （格菲妥单抗）是一种新颖的具有独特2:1结构的双特异性抗体，目前已在华获批，用于治疗既往接受过至少两线系统性治疗的复发或难治性弥漫大B细胞淋巴瘤（DLBCL）成人患者。今年六月，高罗华 ® 的两线适应症数据starglo在欧洲血液年会（EHA）上重磅发布，据此数据中国有望成为在全球范围内最早获批该适应症的国家之一，尽早惠及更多中国复发难治的淋巴瘤患者。 作为最早进入中国的跨国企业之一，罗氏始终致力于为中国患者提供一流的差异化药物和创新解决方案。未来，罗氏将持续依托进博会这一高水平对外开放的平台，加大对华投资，深化创新合作，共享全球经验，助力实现"健康中国2030"宏伟蓝图。

iStock, JHVEPhoto Oditrasertib, which blocks the inflammatory RIPK1 protein, earlier this year also failed a Phase II trial in amyotrophic lateral sclerosis, forcing the company to discontinue its development a few months later. Sanofi is discontinuing a Phase II multiple sclerosis study of its investigational RIPK1 blocker oditrasertib after the candidate failed to meet its primary and key secondary endpoints, according to an SEC filing on Thursday by partner Denali Therapeutics. Denali and Sanofi were evaluating oditrasertib in the mid-stage K2 study , a randomized, double-blinded and placebo-controlled trial that enrolled more than 170 patients with relapsing-remitting multiple sclerosis (MS), secondary progressive MS or primary progressive MS. The primary efficacy endpoint was oditrasertib’s effect on serum neurofilament light chain levels. No specific details were provided in Denali’s SEC document, nor did the company identify which particular secondary outcomes oditrasertib missed. The California biotech also did not address oditrasertib’s safety profile. Designed to be orally available, oditrasertib is an investigational inhibitor of the RIPK1 protein, which is a crucial signaling player in inflammatory and cell death pathways. In neurodegenerative diseases, RIPK1—along with other proteins from the same family— tends to be overactivated , leading to widespread inflammation and large-scale cell death in the brain. By targeting RIPK1, oditrasertib disrupts this pathological process, in turn preserving the integrity and function of the brain. Despite a promising mechanism of action, however, oditrasertib has had a challenging clinical showing recently. In April 2024, Sanofi announced plans to terminate a Phase II trial of oditrasertib in amyotrophic lateral sclerosis (ALS) after a disappointing mid-stage readout. A few months earlier, in February 2024, Sanofi and Denali announced that oditrasertib failed the Phase II HIMALAYA study in ALS , unable to significantly improve disease severity, as measured by the ALS Functional Rating Scale-Revised. Developing effective therapies for MS has proven difficult. In September 2024, another Sanofi asset, the BTK inhibitor tolebrutinib, failed to significantly improve relapse rates in two Phase III studies. Tolebrutinib redeemed itself a few weeks later by significantly delaying disability onset in patients with non-relapsing secondary progressive MS in a third Phase III trial. That same month, a study published in the peer-reviewed journal Neurology raised questions about the use of anti-CD20 antibodies in multiple sclerosis. According to its findings, there appear to be no significant difference in relapse or the progression of disability between patients who were given these therapies versus those who were untreated. The study focused on primary progressive multiple sclerosis, for which the only approved anti-CD20 therapy is Roche’s Ocrevus (ocrelizumab). Other agents in the same drug class are also approved for relapsing forms of MS, including Novartis’ Kesimpta (ofatumumab) and TG Therapeutics’ Briumvi (ublituximab).

THURSDAY, Sept. 26, 2024 -- For patients with primary progressive multiple sclerosis (PPMS), the time to confirmed disability progression (CDP) does not differ for those who are anti-CD20-treated and untreated, according to a study published online Sept. 25 in Neurology . Marion Hay, M.D., from Rennes University Hospital in France, and colleagues analyzed CDP in a cohort of patients with PPMS treated with anti-CD20 therapies versus a weighted untreated control cohort in a retrospective study using data from the French MS registry. A total of 1,184 patients met the inclusion criteria: 426 treated and 758 untreated (median age, 56 years; 52.7 percent female). Among treated patients, 295 and 131 received rituximab and ocrelizumab, respectively. The researchers found that anti-CD20-treated patients were younger and had more active disease at baseline. There was no statistical difference observed in time to first CDP. A nonsignificant trend toward fewer patients relapsing in the treated group was observed in time to first relapse analysis. No significant difference was seen between the two groups for magnetic resonance imaging activity. Male sex and MS duration were risk factors associated with CDP in the treated group. Serious infection incidence ratios were 6.67 and 2.67 per 100 person-years in the treated and untreated groups, respectively. "Our results indicate that there should be a constant evaluation of all available data to ascertain the best risk/benefit ratio for patients with PPMS, especially for newly diagnosed patients for whom inflammatory activity is very often not well defined," the authors write. Several authors disclosed ties to the pharmaceutical industry.