A study to examine the safety (and potential efficacy) of the adult stem cell investigational product, MultiStem, in adults who have Acute Respiratory Distress Syndrome (ARDS). The primary hypothesis is that MultiStem will be safe in ARDS patients.

开始日期2016-01-01

申办/合作机构

Healios KK

[+2]

NCT02277613 / Terminated临床2期

A Phase 2 Prospective, Randomized, Double-blind, Sham-controlled, Parallel-group, Multi-center Trial of AMI MultiStem® Therapy in Subjects With Non-ST Elevation Acute Myocardial Infarction

This is a double-blind, sham-controlled clinical study to evaluate the safety and feasibility of AMI MultiStem therapy in subjects who have had a heart attack (Non-ST elevation MI).

开始日期2015-12-01

申办/合作机构

Athersys, Inc.

[+1]

NCT01240915 / Completed临床2期

A Phase 2 Randomized, Double-blind, Placebo-controlled, Parallel Group, Multi-center Study To Investigate The Safety And Efficacy Of Multistem (Pf-05285401) In Subjects With Moderate To Severe Ulcerative Colitis

MultiStem(r) is a new biological product, manufactured from human stem cells obtained from adult bone marrow or other nonembryonic tissue sources. Factors expressed by MultiStem cells are believed to reduce inflammation and regulate immune system function, protect damaged or injured cells and tissue, promote formation of new blood vessels, and augment tissue repair and healing. MultiStem cell treatment resulted in significant efficacy in a mouse model of Graft versus Host Disease with almost complete reversal of gastrointestinal pathology (similar to pathology that would be expected in Ulcerative Colitis). These data, together with safety data generated in 2 other clinical trials, suggest that MultiStem has the potential to be a new treatment option for patients with ulcerative colitis. This is the first study of MultiStem in this patient population and will cautiously explore the safety/toleration and potential benefit of this new treatment in patients with moderate to severe disease.

开始日期2011-02-01

申办/合作机构

Pfizer Inc.

[+2]

100 项与 Athersys, Inc. 相关的临床结果

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项与 Athersys, Inc. 相关的文献（医药）

2023-01-01·Frontiers in bioengineering and biotechnology

Delivery of multipotent adult progenitor cells via a functionalized plasma polymerized surface accelerates healing of murine diabetic wounds.

Article

作者: Ting, A E ; Kirby, G T ; Smith, L E ; Cowin, A J ; Vaes, B ; Hofma, B R ; Short, R ; Mills, S J ; Statham, P

Introduction: Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. Methods: We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Results and discussion: Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds.

2022-01-01·Intensive care medicine1区 · 医学

Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial

1区 · 医学

Article

作者: McVerry, B J ; Young, D ; Bannard-Smith, J ; Doerschug, K C ; Thickett, D ; Brealey, D ; Summers, C ; Jenkins, E D ; Jacono, F ; Bentley, A ; Wunderink, R G ; Rojas, M ; Bellingan, G ; Meyer, N ; Ting, A

PURPOSE:

Bone marrow-derived, allogeneic, multipotent adult progenitor cells demonstrated safety and efficacy in preclinical models of acute respiratory distress syndrome (ARDS).

METHODS:

This phase 1/2 trial evaluated the safety and tolerability of intravenous multipotent adult progenitor cells in patients with moderate-to-severe ARDS in 12 UK and USA centres. Cohorts 1 and 2 were open-label, evaluating acute safety in three subjects receiving 300 or 900 million cells, respectively. Cohort 3 was a randomised, double-blind, placebo-controlled parallel trial infusing 900 million cells (n = 20) or placebo (n = 10) within 96 h of ARDS diagnosis. Primary outcomes were safety and tolerability. Secondary endpoints included clinical outcomes, quality of life (QoL) and plasma biomarkers.

RESULTS:

No allergic or serious adverse reactions were associated with cell therapy in any cohort. At baseline, the cohort 3 cell group had less severe hypoxia. For cohort 3, 28-day mortality was 25% for cell vs. 45% for placebo recipients. Median 28-day free from intensive care unit (ICU) and ventilator-free days in the cell vs. placebo group were 12.5 (IQR 0,18.5) vs. 4.5 (IQR 0,16.8) and 18.5 (IQR 0,22) vs. 6.5 (IQR 0,18.3), respectively. A prospectively defined severe ARDS subpopulation (PaO₂/FiO₂ < 150 mmHg (20 kPa); n = 16) showed similar trends in mortality, ICU-free days and ventilator-free days favouring cell therapy. Cell recipients showed greater recovery of QoL through Day 365.

CONCLUSIONS:

Multipotent adult progenitor cells were safe and well tolerated in ARDS. The clinical outcomes warrant larger trials to evaluate the therapeutic efficacy and optimal patient population.

2021-11-01·Stem cells (Dayton, Ohio)

Human Multipotent Adult Progenitor Cells Effectively Reduce Graft-vs-Host Disease While Preserving Graft-Vs-Leukemia Activity

Article

作者: Metheny, Leland ; Lazarus, Hillard M. ; Wilson, David ; Auletta, Jeffery J. ; Liu, Chen ; Lee, ZhengHong ; Wuttisarnwattana, Patiwet ; Paez, Conner ; Eid, Saada ; Van Dervort, Alana ; Vant Hof, Wouter ; Deans, Robert ; Cooke, Kenneth R. ; Ktena, Yiouli

Abstract:

Graft-vs-host disease (GvHD) limits successful outcomes following allogeneic blood and marrow transplantation (allo-BMT). We examined whether the administration of human, bone marrow-derived, multipotent adult progenitor cells (MAPCs™) could regulate experimental GvHD. The immunoregulatory capacity of MAPC cells was evaluated in vivo using established murine GvHD models. Injection of MAPC cells on day +1 (D1) and +4 (D4) significantly reduced T-cell expansion and the numbers of donor-derived, Tumor Necrosis Factor Alpha (TNFα) and Interferon Gamma (IFNγ)-producing, CD4+ and CD8+ cells by D10 compared with untreated controls. These findings were associated with reductions in serum levels of TNFα and IFNγ, intestinal and hepatic inflammation and systemic GvHD as measured by survival and clinical score. Biodistribution studies showed that MAPC cells tracked from the lung and to the liver, spleen, and mesenteric nodes within 24 hours after injection. MAPC cells inhibited mouse T-cell proliferation in vitro and this effect was associated with reduced T-cell activation and inflammatory cytokine secretion and robust increases in the concentrations of Prostaglandin E2 (PGE2) and Transforming Growth Factor Beta (TGFβ). Indomethacin and E-prostanoid 2 (EP2) receptor antagonism both reversed while EP2 agonism restored MAPC cell-mediated in vitro T-cell suppression, confirming the role for PGE2. Furthermore, cyclo-oxygenase inhibition following allo-BMT abrogated the protective effects of MAPC cells. Importantly, MAPC cells had no effect on the generation cytotoxic T lymphocyte activity in vitro, and the administration of MAPC cells in the setting of leukemic challenge resulted in superior leukemia-free survival. Collectively, these data provide valuable information regarding the biodistribution and regulatory capacity of MAPC cells, which may inform future clinical trial design.

项与 Athersys, Inc. 相关的新闻（医药）

2024-06-05

·行舟Drug

罕见病用药保障现状与挑战

点击上方的行舟Drug ▲ 添加关注罕见病用药保障现状与挑战来源《罕见病研究》 2024, 3 ( 2): 155⁃ 163 作者左玮，张波，张抒扬中国医学科学院北京协和医院，药剂科，心内科；疑难重症及罕见病全国重点实验室，国家罕见病医疗质量控制中心摘要近年来，国家和政府的高度重视有效推动了中国罕见病诊疗和保障工作。但全球范围内，仅5%的罕见病存在有效治疗方法。罕见病药物可及性差仍是中国罕见病领域存在的主要困境之一，是导致患者“治疗难”和“用药难”主要原因。罕见病药物保障覆盖罕见病药物研发、生产、流通、使用、支付保障、技术创新等多个环节，涉及供给、需求、政策决策等多个主体，其复杂性不同于普通药物。本文总结国内外罕见病药物保障政策，以及目前罕见病药物治疗的技术和方法，提出存在的问题和挑战，以期对未来罕见病药物保障和技术的创新和发展做出展望。关键词罕见病；孤儿药；用药保障；药品支付；审评审批 _ 正文 _ 罕见病单病种发病率低、病情复杂、诊断难度大，导致罕见病药物临床研发面临诸多困难[1]。据统计，70%~80%的罕见病由遗传因素导致，高达95%的罕见病尚无有效治疗措施[2]。从全球现状来看，罕见病患者可用的治疗方法包括药物、饮食、手术或医疗器械等，而药物治疗是其中最主要的治疗方式[3]，罕见病药物可及性程度直接决定着患者的生存状况甚至生存时间。完善罕见病用药保障政策，提高罕见病患者药品可及性是实现健康中国战略的关键措施之一。 1 国际罕见病用药保障现状 1.1 罕见病药品审评审批为了满足罕见病人群的用药需求，世界主要国家和地区监管机构陆续出台了一系列加快药品上市注册的政策，以实现高效和有效地开发治疗罕见疾病的药物。1983年，美国食品药品监督管理局（Food and Drug Administration，FDA）通过的《孤儿药法案》为制药公司开发罕见疾病疗法提供了激励，如税收抵免、7年的市场专营期、孤儿药研发项目研究补助资金、免除孤儿药新药申请费，以及与监管机构密切合作的机会等[4]。在实施《孤儿药法案》前，只有10种药物被批准用于治疗罕见疾病[5]。自1983—2021年底，美国FDA共授予了6143个孤儿药认定，其中有1033个孤儿药适应证获批上市[6]。2022年美国FDA药品评价与研究中心（Center for Drug Evaluation and Research，CDER）批准的37款新药中，有18种（48.6%，18/37）获得孤儿药认定[7]，2023年美国FDA批准的55种新药中，有28种（50.9%，28/55）获得孤儿药认定[8]。与《孤儿药法案》类似，欧盟于1999年通过了《孤儿药品条例》[9]，激励了罕见疾病疗法的开发，且与美国FDA相比将享有更长的市场独占权（10年）。但也有研究显示尽管美国FDA和欧洲药品管理局（European Medicines Agency，EMA）孤儿药认定的标准相似，但实施路径不尽相同，如被美国FDA认定的孤儿药中，只有不到50%同时获得了EMA的孤儿药认定[10]。除了孤儿药认定，不同国家和地区还允许对包括罕见病用药在内的创新和有效的药物治疗进行加速审查。如美国国会授权FDA通过快速通道、加速审批、优先审评和突破性疗法等特殊认定和审评途径，促进和加快对严重疾病的药物，特别是罕见病药物的研发，以解决尚未被满足的医疗需求[6]。2020年，美国CDER批准的53种新药中，获得孤儿药认定的抗肿瘤药占比85%。此外，批准的新药中有36种使用过一项或多项加急计划，这其中获得孤儿药认定的新药占80.6%。其他国家和地区也引入多种新药审批途径，加快了药物的批准时间。如新药获得美国FDA优先审评后，其审评时间较标准审评时间的10个月缩短为4个月[6]。欧盟人用药品委员会接受加速审评申请后，该药品的审查周期可从210d缩短为150d[11]。在日本，获得先驱策略认定的创新药品，总审查期从常规路径的12个月缩短为6个月[12]。 1.2 罕见病药品支付罕见病人群较少，且往往表现出较大的疾病异质性，使获得高质量临床疗效和成本效益的相关证据更为困难[13]。美国采用部分偿付报销制度，其中老年与残障健康保险中的补充医疗保险和处方药计划，为其承保药品清单内罕见病用药提供偿付报销[14]。在欧盟，罕见病用药偿付报销情况由各成员国自主制定，但普遍不需要进行成本效益分析。比利时在2004年7月颁布了8号皇家法令，明确不将罕见病用药的经济性评价纳入到考虑范围内，大部分罕见病用药获得100%的报销[15]。在法国，同样不需要成本效益分析，其门诊药品的报销比例通常取决于药品的临床效益与疾病严重程度[15]。罕见病属于严重疾病，门诊期间用于治疗的罕见病用药可获得65%或100%的偿付报销；而在住院期间，罕见病患者所使用的罕见病用药可获得100%的偿付报销[15]。在德国，若药品获得了罕见病药物认证，则自动被视为具有额外效益，无需与替代疗法进行必要的比较，直接与国家法定医保基金联合会进行医保报销价格的谈判。但当罕见病药物的年销售额超过5000万欧元时，该药物不再享有特权，并且药企必须在3个月内向联邦联合委员会提交完整的药物档案，包括比较分析的数据[15]。目前各国学者也在寻找孤儿药新的可替代评估方法，例如，波兰正在考虑在其卫生技术评估政策中使用多准则决策分析（multi⁃criteria decision analysis，MCDA）[15]。文章内容由凡默谷小编查阅文献选取，排版与编辑为原创。如转载，请尊重劳动成果，注明【来源：凡默谷公众号】。 2 中国罕见病用药保障现状 2.1 罕见病药品研发和审评审批自“十三五”以来，中国针对罕见病预防诊疗、药品研发及注册审评、生产流通、患者医疗保障等，陆续颁布多项鼓励罕见病药物研发和上市的政策，其中包括加快罕见病药物审评审批、减免临床和附条件上市、给予罕见病药物6年数据保护期等。2018年5月和2023年9月，国家卫生健康委员会等多部门联合发布《第一批罕见病目录》和《第二批罕见病目录》[16⁃17]，共纳入207种罕见病。以上目录的发布对于罕见病治疗药物的可及性与可获得性、新药和仿制药的研发，以及医保目录的调整等起到了极大的推动作用。此外，自2018年以来，国家药品监督管理局药品审评中心发布3批临床急需境外新药名单，共涉及73种临床急需境外新药，其中41种药物为罕见病用药[18⁃20]。系列目录的制定，成为中国执行罕见病相关审评审批政策的参考基础。截至2022年第一季度，国家药品监督管理局药品审评中心共将137种罕见病药物正式纳入优先审评，且数量呈逐年增长趋势。 2.2 罕见病药品可及性的中国式探索针对罕见病药品短缺问题，国务院于2013年批准设立海南博鳌乐城国际医疗旅游先行区，允许区内特定医疗机构因临床急需而进口在海外已批准上市但尚未在中国获批且无法替代的药品，以更好地满足中国罕见病患者的需求。探索临床急需用药的一次性进口特购也是解决罕见病“用药难”的一个重要方法。2023年，国务院关于《支持北京深化国家服务业扩大开放综合示范区建设工作方案》的批复中指出，优化跨境贸易监管服务模式，支持在北京天竺综合保税区建立罕见病药品保障先行区，探索进口未在国内注册上市的罕见病药品，由特定医疗机构指导药品使用，是对中国罕见病治疗保障的又一次重大提升。 2.3 罕见病药品支付 2019年，财政部、海关总署、税务总局和药品监督管理局四部门联合下发《关于罕见病药品增值税政策的通知》（财税〔2019〕24号）税收优惠政策，保障罕见病药品供应[21]。截至2022年底，中国已发布3批适用增值税政策的罕见病药品清单，包括54种制剂和5种原料药。2020年《中共中央国务院关于深化医疗保障制度改革的意见》（中发〔2020〕5号）[22]明确要求，要建成以基本医疗保险为主体，医疗救助为托底，补充医疗保险、商业健康保险、慈善捐赠、医疗互助共同发展的医疗保障制度体系。医保准入方面，国家医疗保障局通过专家遴选的方式将部分罕见病用药纳入国家基本医保药品目录，对部分价格比较昂贵的罕见病用药通过国家谈判的方式进行筛选纳入。针对《第一批罕见病目录》121种疾病，截至2023年6月底，在中国上市的罕见病药物有75种，纳入医保药品目录的有50种，其中通过准入谈判纳入国家医保目录的累计26种，平均降价超50%。2023年9月中国发布了《第二批罕见病目录》，收录86种疾病，涉及36种药物，其中已有13种被成功纳入医保。2024年1月实施的新版医保目录，新纳入罕见病用药15种。越来越多的罕见病用药纳入目录，患者治疗负担大幅减轻。 3 罕见病的药物治疗准确诊断和及时治疗罕见病是临床医师面临的共同挑战。遗传缺陷是导致罕见病的重要因素。遗传性罕见病的治疗方法包括食疗、手术、药物治疗、骨髓移植和医疗器械辅助治疗等。小分子药物治疗、抗体治疗、蛋白质替代治疗、基因治疗、造血干细胞治疗和药物再利用等是目前用于治疗罕见疾病主要方式[23]。近年来基因治疗、干细胞治疗等新的研究热点的出现，改变了许多复杂疾病的治疗模式，给罕见病患者带来了新的希望。 3.1 创新药/创新疗法开发 3.1.1 小分子药物治疗小分子药物主要是指化学合成的、分子量小于1000的有机化合物。人类基因组中估计有3000种与疾病相关的蛋白质，目前只有不到700种作为获批药物的治疗靶点[24]。合成化学、高通量筛选、虚拟筛选、基于结构的药物设计，以及基于片段的药物设计等小分子药物研发技术的进步，正在使新的生物活性分子的发现和设计成为可能[25]。美国FDA发布的2023年批准新药报告显示，2023年美国CDER批准的55种创新药中包括33种小分子药物[8]，其中小分子药物孤儿药有13种。靶向筛选和更好的疾病建模推动了小分子药物在罕见病治疗中的成功。例如，囊性纤维化（cystic fibrosis，CF）是由CFTR基因突变导致的CFTR蛋白功能缺陷和/或缺失引起的罕见遗传病。该疾病的治疗性小分子药物ivacaftor已经从细胞中筛选获得。其最初被批准用于治疗CF患者的10种不同突变，随后批准扩大到33种突变[26]。理论上小分子化合物拥有靶向所有组织的潜力，目前仍是医药领域的主力之一。 3.1.2 抗体治疗抗体治疗是一种通过被动免疫发挥作用的治疗方法。目前治疗性单克隆抗体，如Fc融合蛋白、抗体片段和抗体⁃药物偶联物等已广泛应用于多个治疗领域，特别是抗肿瘤治疗[27]。虽然目前针对罕见病的单抗类治疗药物数量有限，但抗体疗法的潜力逐步得到重视。如依库珠单抗（eculizumab）在2007年首次被美国FDA批准用于治疗阵发性睡眠性血红蛋白尿，此后又被批准用于治疗补体系统起重要作用的其他罕见疾病，包括非典型溶血性尿毒症综合征、抗乙酰胆碱受体抗体阳性的难治性重症肌无力及抗水通道蛋白抗体阳性的视神经脊髓炎谱系疾病[23]。由于单抗体积大，穿透和积累组织的能力有限，限制了其应用于临床。2018年9月，全球首款纳米抗体药物cablivi获得EMA批准，用于获得性血栓性血小板减少性紫癜成人患者的治疗[27]。单抗药物也有影响其临床使用的局限性。其中，最突出的挑战是单抗在制造、运输和储存过程中的短药代动力学特性和稳定性问题。 3.1.3 蛋白质替代疗法蛋白质替代疗法长期以来一直是治疗与特定蛋白质功能丧失相关罕见疾病的基石。过去几十年以来，从血浆衍生产品（因子Ⅷ或因子Ⅸ用于血友病A或血友病B的治疗）到重组蛋白（多肽类激素、细胞因子、酶替代等），再到重组工程化蛋白（如聚乙二醇化修饰蛋白）等，在这一领域不断出现重大创新[28]。近年来，酶替代疗法（enzyme replacement ther⁃apy，ERT）广泛用于溶酶体贮积病（lysosomal storage disease，LSD）[29]、α1⁃抗胰蛋白酶缺乏症[30]、腺苷脱氨酶缺乏相关的重症联合免疫缺陷病[31]及苯丙酮尿症等罕见病的治疗。如重组ERTs已被开发并批准用于11种不同的LSD，包括戈谢病、法布雷病、黏多糖贮积症Ⅰ型、α⁃甘露糖苷贮积症等。ERT具有技术发展较好、安全性较高的优点。但也存在生物药物在体内的组织分布情况尚不明确、难以通过血脑屏障、治疗费用昂贵等问题。 3.1.4 基因治疗罕见病通常为单基因病，是最适合使用基因治疗攻克的疾病。广义的基因治疗药物包括基于DNA修饰的DNA药物与RNA药物[32]。2022年美国CDER批准了4种基因疗法，2023年CDER共批准了5种基因疗法[8]。基于腺相关病毒的疗法已证明对多种疾病具有临床疗效，包括脊髓性肌萎缩症（spinal mus⁃cular atrophies，SMA）、血友病A和血友病B、芳香族L⁃氨基酸脱羧酶缺乏症和视网膜色素上皮特异性65kDa蛋白介导的视网膜变性等[33⁃34]。另一种针对疾病相关基因的广泛策略是在RNA水平上进行干预，通过促进mRNA降解来减少特定疾病相关蛋白的产生[35]，原则上任何基因产物都可以作为靶标，大大扩展了可选靶点的数量和类型。如诺西那生就是一种反义寡核苷酸类药物，可通过增加全功能运动神经元生存蛋白的生成来治疗SMA。然而，寡核苷酸不易穿过血脑屏障，因此需要侵入性的递送方法，如鞘内或脑室内途径等。RNA干扰技术（RNA interference，RNAi）的出现，使得治疗部分罕见病更有希望。例如，英克司兰（inclisiran）是已被美国FDA批准的利用RNAi技术治疗原发性高胆固醇血症的药物[36]。基因编辑工具也是基因治疗领域另一核心讨论方向，casgevy是全球首个获批应用的CRISPR基因疗法，可用于治疗镰状细胞病和输血依赖性β地中海贫血[37]。基因疗法长期潜在的不良反应，以及昂贵的价格仍是目前限制其应用的主要原因。 3.1.5 造血干细胞治疗造血干细胞移植是一种利用人类细胞调节免疫系统，重建患者正常造血及免疫功能的治疗方式。造血干细胞移植有多种途径，包括骨髓移植、外周血造血干细胞移植和脐带血移植等。干细胞治疗原发性罕见病疗效显著，给免疫缺陷综合征、异染性脑白质营养不良、慢性肉芽肿病、IgE综合征和多种溶酶体贮积性疾病（黏多糖贮积症、戈谢病、尼曼匹克病等）等罕见疾病带来了希望[38]。黏多糖贮积症Ⅰ型是一种常染色体隐性遗传的罕见病，由α⁃L⁃艾杜糖苷酸酶缺乏引起，可导致体内所有器官和组织中糖胺聚糖过量蓄积，进而危及生命。目前的治疗方法有ERT和造血干细胞移植[39]。ERT即在静脉内注射患者缺乏的重组黏多糖水解酶，但该酶在血液中半衰期很短，且不能透过血脑屏障。而造血干细胞移植后能够持续补充患者所缺乏的酶，且分化后能够透过血脑屏障在中枢神经系统中发挥作用。2012年美国FDA批准Athersys公司研发的间充质干细胞疗法MultiStemⓇ用于治疗黏多糖贮积症Ⅰ型。 3.2 已上市药物的罕见病适应证开发药物再利用，指将某一种已被批准用于治疗某种疾病的药物，重新用于治疗其他不同疾病的治疗策略[40]。药物再开发的机会往往来自于偶然的临床观察、“同情用药”和超适应证用药处方等。大多数重新利用的化合物已在人体中证明了安全性，因此这种方法可以加速药物研发过程。如西地那非和阿达木单抗，二者最初均批准用于常见疾病，随后又获得了罕见疾病适应证的额外批准[41⁃42]。不同国家和地区均建立有效方法来助力药物再开发。如国际罕见病研究联盟已初步建立方法来识别现有化合物在罕见病中的再开发机会。美国国家转化科学促进中心还专门开发了可供再开发参考的药物集合，其中包括获美国FDA批准上市的约2500种化合物和批准用于人类临床研究的1000种化合物[43]。美国麻省理工学院和哈佛大学⁃博德研究所共享药物再开发筛选库，其中涵盖约6000种化合物的综合注释，包括约2300种已获批药物和约1600种临床在研药物[44]。在此基础上，借助高通量及高内涵药物筛选技术、药物设计和虚拟筛选技术、靶点对接筛选技术等，可从已经上市的药物中发现新的作用机制，定位新的用途，研发新的药物。此外，中国有大量临床实践的积累，正确而恰当地开展真实世界研究，也是目前中国国情下“老药”开发罕见病适应证实际且可行的方式。但需要注意的是，虽然再开发的候选药物可能有更大的成功概率和更低的开发成本，但仍需要进行临床试验来证明对新适应证的有效性，特别是当新适应证（如合并症）或治疗方案（如长期与短期）存在一系列不同特殊背景时，药物的安全性特征可能会显著改变。 4 罕见病药学研究和服务的协和探索 4.1 “一次性进口”路径探索在国家有关部门的指导和支持下，北京协和医院建立了罕见病药学研究和服务体系，不断推动罕见病药物可及性和合理用药水平提升。为了满足中国患者的用药需求，北京协和医院先后向主管单位提出申请，以“一次性进口”的方式购买治疗肾上腺皮质癌药物米托坦片和难治性癫痫的氯巴占片。为保障一次性进口药品的合理使用，医院多科室积极联动，共同起草北京协和医院临时进口药品《临床使用指南》《管理办法》《患者用药知情同意书》等10余项文件，建立了多学科诊疗团队，从治疗方案制订、临床疗效评估、药物相互作用、不良反应监控、血药浓度监测和结果解读等多角度、全方位做好患者个体化及规范治疗的管理。此外，北京协和医院罕见病多学科诊疗团队专家依据循证医学证据，结合实践经验制定的《米托坦治疗肾上腺皮质癌专家共识（2021）》[45]和《氯巴占治疗难治性癫痫专家共识》[46]，为促进一次性进口药品的规范化、合理化及临床用药提供参考。 4.2 精准和安全用药监测平台为推动罕见病用药精准性、安全性，建立了罕见病精准用药平台，先后建立米托坦[47]、利鲁唑[48]、氯巴占/去甲氯巴占、诺西那生钠等罕见病药物的体内药物浓度检测方法，积极开展精准用药研究。临床用药过程中，研究团队深入探讨了影响中国肾上腺皮质癌患者米托坦血药浓度的因素，特别关注米托坦代谢酶基因型多态性在其中的作用，为进一步指导临床合理应用米托坦提供依据[49]。在罕见病药物真实世界研究方面，团队聚焦罕见病药物不良反应研究，基于自发呈报系统数据库和真实世界数据回顾性分析，发现了罕见病药物相关新的和罕见药物不良反应，如丝裂原活化细胞外信号调节激酶抑制剂致视网膜静脉阻塞[50]；利鲁唑相关的低钠血症和不适当的抗利尿激素分泌[51]；氯巴占所致的严重皮肤不良反应、呼吸系统感染和基于CYP3A4/2C19的药物相互作用[52]等。此外，针对中国一次性进口罕见病药物米托坦片开展不良反应真实世界研究[53]，为罕见病药物的安全性提供数据支持和参考。 4.3 “同情用药”探索 2017年12月由原国家食品药品监督管理总局公布《拓展性同情使用临床试验用药物管理办法（征求意见稿）》[54]。2019年8月修订的《中华人民共和国药品管理法》第二十三条规定[55]：“对正在开展临床试验的用于治疗严重危及生命且尚无有效治疗手段的疾病的药物，经医学观察可能获益，并且符合伦理原则的，经审查、知情同意后可以在开展临床试验的机构内用于其他病情相同的患者”。2021年中国首例罕见病“同情用药”在北京协和医院落地，将一种在国外研发还处于Ⅲ期临床试验阶段的药物用于患有阵发性睡眠性血红蛋白尿的罕见病患者。这是中国首例罕见病“同情用药”，这一案例探索了罕见病药品可及性的创新机制和路径，为更多类似患者获得罕见病药物起到了示范作用。 5 罕见病用药保障的挑战和展望在罕见病药物的研究方面，仍有很大一部分尚未到达临床阶段，甚至结束于临床前阶段，获批的孤儿药只解决了一小部分罕见病，仍有95%的罕见病患者“无药可医”。另外，还有一个不容忽视的问题是超过1/3的获批孤儿药是针对肿瘤领域。未来如何将罕见病的基础研究转化为临床疗法，必须成为公共和慈善基金中更高的优先事项。同时，对于罕见孤儿药，特别是超罕见孤儿药的临床试验要更加复杂。因此，需要更多的研发资助和政府不同机构间更密切的合作等政策来鼓励开发。如美国发布的《21世纪治愈法案》[56]，以及中国国家药品监督管理局发布的《药物真实世界研究与方案框架指导原则（试行）》[57]等，均鼓励使用新的“药物开发工具”，如非传统临床试验、新的数据分析方法、真实世界证据、观察性研究、生物标志物和替代终点作为药物审评的依据，以加快某些药物的批准时间。目前，世界主要发达国家和地区已经通过开展罕见病患者注册登记研究来支持罕见病的临床研究和新药临床试验，如遗传病和罕见病信息中心、欧盟的罕见病和罕见病药物网站Orphanet、美国罕见病组织、中国的罕见病注册登记系统等。在未来，如何建立和选择科学研究方法，充分挖掘和利用现有真实世界数据，将对推动罕见病用药保障起到至关重要的作用。孤儿药的审批路线在加快药品上市的同时，也带来诸多挑战。1999—2018年的一项纵向研究发现，在214种孤儿药中，69%的药物在获批后，其标签上的安全部分发生变化。其中15%为严重安全事件，如停药、警告或暂停[58]。另一项研究发现，87%孤儿药在获得EMA批准后发生了严重的安全事件[59]。Berlin[60]的研究发现，优先审评批准的药物在美国FDA批准后进行标签修订的可能性是标准审评批准药物的两倍。获得孤儿药认定资格的药品部分安全性问题可归因于试验设计。研究发现，孤儿药的批准更多依赖于非随机开放标签的单臂试验，只研究了非孤儿药试验所需人群的一半[61]。一方面，用药保障研究导致不良事件的归因、安全性特征的分析可能存在偏倚；另一方面，药物安全性特征的表征主要依赖于受试人群的暴露量，而罕见病药物研发中，临床试验的安全性整体暴露可能不足。这些都可能导致罕见病药物上市后的风险。虽然一些国家和地区针对部分不满足常规审批标准的药品采取附条件批准上市，要求上市后继续提供额外的安全性和有效性随访数据，并接受审查，但由于罕见病本身发病率低，其安全性亟需引起国家监管和临床诊疗层面的关注。在未来，中国应发挥在罕见病领域的人口优势，依托罕见病等级系统，探索和建立一条科学、全面、系统的，且具有中国特色的罕见病药物警戒体系之路，提升临床合理用药水平，提高公众的生活质量，保障公众用药安全。罕见病保障机制建设是一项系统工程，涉及国家卫生健康委员会、药品监督管理局、医疗保障局、工业和信息化部、科学技术部和财政部等多个主管部门。不同部门之间的协同配合，是中国罕见病药品供应保障的重要条件。未来需要以罕见病目录为抓手，加强部门协同和政策联动，统筹推进；加强罕见病领域所有利益相关方的密切合作，确保罕见病用药保障的协同顺畅。此外，与发达国家相比，中国在创新药物和罕见病药物的支付标准上仍存在一定差距，但这一差距会随着医保政策的完善和支付能力的提升而逐渐缩小。中国相对较大的罕见病人群规模为药物研发企业提供了市场优势，加上医保政策的持续引导和科学化、系统化的管理，都将为提高罕见病药物可负担性创造有利的发展条件。参考文献详见《罕见病研究》 2024, 3 ( 2): 155⁃ 163 文章信息源于公众号凡默谷，登载该文章目的为更广泛的传递行业信息，不代表赞同其观点或对其真实性负责。文章版权归原作者及原出处所有，文章内容仅供参考。本网拥有对此声明的最终解释权，若无意侵犯版权，请联系小编删除。学如逆水行舟，不进则退；心似平原走马，易放难收。行舟Drug 每日更新欢迎订阅+ 医药大数据|行业动态|政策解读

孤儿药快速通道

2024-04-03

·BioSpace

Acorda Joins Growing Group of Biotechs Filing for Bankruptcy, Divests Assets to Merz

Pictured: Man holding a Chapter 11 bankruptcy filing/iStock, designer491 Acorda Therapeutics on Monday announced that it has voluntarily filed for bankruptcy and is seeking Chapter 11 protections to facilitate the orderly transfer of its assets and the winding down of its business operations. The company has also entered into an asset purchase agreement with German biotech Merz Therapeutics, which has agreed to acquire “substantially all” of Acorda’s assets, including its FDA-approved drugs Inbrija (levodopa inhalation powder), Ampyra (dalfampiridine) and Fampyra (fampiridine), for $185 million. The sale will take place through a competitive auction process, with Merz acting as a “stalking horse” bidder. Acorda’s shares tanked 59% in after-hours trading in reaction to the news, according to Seeking Alpha. The decision to Chapter 11 bankruptcy was made “following an exhaustive process” and lengthy strategic review of its options for the business moving forward, CEO Ron Cohen said in a statement. Acorda contends that filing for bankruptcy “is in the best interest” of stakeholders. “One of our top priorities is to ensure an uninterrupted supply of our medications to people with multiple sclerosis and Parkinson’s disease,” Cohen added. “We are confident that Merz Therapeutics, if they are the ultimate acquirer, will be able to seamlessly continue serving these patients’ needs.” Acorda’s Chapter 11 proceedings will take place in the U.S. Bankruptcy Court for the Southern District of New York. If the court approves and grants certain protections, Acorda will be able to continue its normal operations as it works to wind down the company’s business. Court approval will also allow Acorda to “minimize” the effects of its bankruptcy on employees, clients, patients and other stakeholders, according to the company. Monday’s bankruptcy announcement puts an end to Acorda’s years of financial struggles. In 2019, the company launched a restructuring initiative that saw 25% of its employees laid off, in an attempt to save $21 million. In September 2021, Acorda slashed its headcount by another 15%, hoping to cut costs by around $20 million per year, starting in 2022. The company at the time also shuffled its masthead, including a change in its CCO and COO positions. In January 2024, Acorda also lost a high-powered partner when Biogen opted to return the ex-U.S. licensing rights over Fampyra. The termination of the partnership is scheduled to take effect on Jan. 1, 2025. With its bankruptcy announcement on Monday, Acorda joins a growing group of biotech companies that have shuttered their businesses this year. On Monday, Eiger BioPharmaceuticals announced that it also filed for Chapter 11 bankruptcy and would wind down its operations. In January 2024, Athersys revealed that it had gone bankrupt and would divest its assets to its research partner Healios. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

并购引进/卖出

2024-03-27

·PRNewswire

Acute Respiratory Distress Syndrome Treatment Market size is set to grow by USD 1.22 bn from 2024-2028, Air Liquide SA, Athersys Inc. & Boston Scientific Corporation, and more to emerge as Some of the Key Vendors, Technavio

NEW YORK, March 27, 2024 /PRNewswire/ -- The global acute respiratory distress syndrome treatment market size is estimated to grow by USD 1.22 bn from 2024 to 2028, according to Technavio. The market is estimated to grow at a CAGR of 6.9% during the forecast period. North America held the largest share of the global market in 2023, and the market in the region is estimated to witness an incremental growth of 39%.To understand more about this market- Download a FREE Sample Report in minutes! Continue Reading Technavio has announced its latest market research report titled Global Acute Respiratory Distress Syndrome Treatment Market 2024-2028 Major Players in the Market Numerous companies are capitalizing on this growing trend by implementing strategic measures such as alliances, partnerships, mergers, and acquisitions. Among the notable players in the cheese based snacks market are: Air Liquide SA, Athersys Inc., Boston Scientific Corporation, Dragerwerk AG and Co. KGaA, Getinge AB, Koninklijke Philips N.V., LivaNova PLC, Medtronic, Nihon Kohden Corp., SCHILLER AG, Sleepnet Corp., Stryker Corp., Vyaire Medical Inc., Smiths Group Plc, ResMed Inc., Hamilton Medical AG, GE Healthcare Technologies Inc., Fisher and Paykel Healthcare Corp. Ltd., Edesa Biotech Inc., APEPTICO Forschung und Entwicklung GmbH Analyst Review The Acute Respiratory Distress Syndrome (ARDS) Treatment Market encompasses various interventions aimed at managing this life-threatening condition. ARDS is often triggered by disease prevalence, such as sepsis or pneumonia, which can lead to fluid accumulation in the lungs and cause symptoms like shortness of breath, rapid breathing, and extreme tiredness. Trade regulations play a crucial role in ensuring access to essential treatments, including mechanical ventilation, IV fluids, inhaled medications, nitric oxide, and surfactants. These therapies help manage symptoms, prevent further lung damage, and maintain vital organ function. The rising prevalence of air pollution and exposure to harmful gases further exacerbate the risk of ARDS. The World Health Organization (WHO) emphasizes the importance of addressing these environmental factors to reduce the burden of ARDS and its associated treatment costs, which can be substantial due to the high prices of drugs like inhaled medications and oxygen therapy. Key Market Drivers The Acute Respiratory Distress Syndrome (ARDS) treatment market is experiencing significant growth due to the increasing prevalence of ARDS, driven by sepsis and pneumonia, as well as rising air pollution and harmful gases leading to lung damage. Reimbursement policies in critical care units of hospitals play a crucial role in market expansion, enabling the use of advanced ventilation strategies, such as lung-protective ventilation, which include low tidal volumes, moderate to high PEEP, and driving pressure optimization. These strategies aim to maintain adequate oxygenation while minimizing ventilator-induced lung injury and barotrauma. Treatment costs, including IV fluids, inhaled medications like nitric oxide and surfactants, and mechanical ventilation, continue to be a challenge. Trade regulations and drug prices also impact market revenue growth. The World Health Organization advocates for evidence-based guidelines, which incorporate lung-protective ventilation strategies into clinical practice, optimizing respiratory support and minimizing complications. Market trends include ongoing research and development of new treatments, offering opportunities for growth, while challenges include the high cost of care and the need for personalized treatment approaches. Symptoms of ARDS include low blood pressure, shortness of breath, rapid breathing, and extreme tiredness, emphasizing the importance of effective treatment strategies. Challenges and Opportunities The Acute Respiratory Distress Syndrome (ARDS) treatment market faces a complex competitive landscape due to the heterogeneity of patients. Technological advancements, such as acoustic technology for endotracheal tube occlusion and ventilator strategies, are driving innovation. Healthcare facilities and specialty clinics are key end users, with home healthcare gaining traction. Government awareness campaigns aim to increase disease recognition, yet a lack of awareness persists. Market segmentation considers patient characteristics, including age, sex, comorbidities, and disease etiology. Diagnosis relies on symptoms like shortness of breath, rapid breathing, low blood pressure, and fluid accumulation in the lungs, often caused by sepsis or pneumonia. Approved drugs and reimbursement policies influence treatment costs, which can be high due to critical care unit admissions and hospitalizations. Trade regulations and disease prevalence further shape the market dynamics. Despite these challenges, ongoing research and investment in ARDS treatments offer hope for improving patient outcomes and reducing the burden on vital organs, including the lungs and alveoli. The Acute Respiratory Distress Syndrome (ARDS) Treatment Market is experiencing significant revenue growth due to the rising incidence of extreme tiredness and respiratory distress caused by various factors, including air pollution and harmful gases. Immunomodulatory therapies, such as IV fluids, inhaled medications, nitric oxide, and surfactants, are crucial in managing ARDS. The World Health Organization (WHO) highlights the importance of multimodal treatment approaches, which include anti-inflammatory agents, antiviral therapies, and respiratory support modalities. Market trends include the use of mechanical ventilation, endotracheal tube occlusion, and acoustic technology to optimize treatment outcomes. Growth drivers include research reports, government awareness campaigns, and healthcare investment. Challenges include lack of awareness, end user reimbursement policies, and the competitive landscape. Approved drugs and ventilator strategies are segmented by specialty clinics, home healthcare, and critical care units. Diagnosis and critical care unit admissions are key factors influencing market size. Technological advancements, such as approved drugs and ventilator strategies, offer opportunities for market expansion.To understand more about this market- Download a FREE Sample Report in minutes! Market Overview The Acute Respiratory Distress Syndrome (ARDS) Treatment Market is experiencing significant growth due to the increasing prevalence of ARDS and the need for effective therapeutic interventions. Drugs, such as surfactants and corticosteroids, are commonly used in ARDS treatment. Preventive measures, like oxygen therapy and prone positioning, are also crucial in managing ARDS symptoms. Additionally, advances in technology, such as extracorporeal membrane oxygenation (ECMO), have revolutionized ARDS treatment, offering new hope for patients. The market is further driven by the rising healthcare expenditures and the increasing awareness and education about ARDS. However, the high cost of these treatments and the lack of reimbursement policies pose challenges to the market's growth. Despite these challenges, the market is expected to continue expanding due to the increasing demand for effective ARDS treatments. Table of Contents: 1 Executive Summary 2 Market Landscape 3 Market Sizing 4 Historic Market Size 5 Five Forces Analysis 6 Market Segmentation 7 Customer Landscape 8 Geographic Landscape 9 Drivers, Challenges, and Trends 10 Venodr Landscape 11 Vendor Analysis 12 Appendix About Technavio Technavio is a leading global technology research and advisory company. Their research and analysis focuses on emerging market trends and provides actionable insights to help businesses identify market opportunities and develop effective strategies to optimize their market positions. With over 500 specialized analysts, Technavio's report library consists of more than 17,000 reports and counting, covering 800 technologies, spanning across 50 countries. Their client base consists of enterprises of all sizes, including more than 100 Fortune 500 companies. This growing client base relies on Technavio's comprehensive coverage, extensive research, and actionable market insights to identify opportunities in existing and potential markets and assess their competitive positions within changing market scenarios. Contacts Technavio Research Jesse Maida Media & Marketing Executive US: +1 844 364 1100 UK: +44 203 893 3200 Email: [email protected] Website: SOURCE Technavio

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2024年12月23日管线快照

管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

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药物(靶点)	适应症	全球最高研发状态

FEN1 inhibitors(Athersys) ( FEN1 )	肿瘤更多	临床前
ATH-0013974 ( FEN1 )	肿瘤更多	临床前
Antitumor agents(Athersys, Inc.)	肿瘤更多	临床前
ATHX-105 ( 5-HT2C receptor )	肥胖更多	终止
Invimestrocel (Athersys)	溃疡性结肠炎更多	无进展