A Prospective, Single-arm Clinical Study on the Efficacy and Safety of DEBIRI Combined With Systemic Chemotherapy and Bevacizumab for Unresectable Colorectal Cancer With Liver Metastases

To study the efficacy and safety of embolization therapy with uniform particle size drug-eluting beads loaded with irinotecan (DEBIRI) in patients with unresectable colorectal cancer liver metastases.

开始日期2024-01-01

申办/合作机构

复旦大学

NCT03369041 / Active, not recruitingN/AIIT

Study of the Practice of Debiri in France: Indications, Associations to Systemic Treatments, Efficiency, Tolerance - Prospective Practice Survey

In order to extract the profiles of patients receiving DEBIRI treatment at best, the investigators proposed the establishment of a national prospective cohort to collect information on the greatest number of patients treated with DEBIRI. This cohort will allow a better understanding of the effectiveness, tolerance, feasibility and differences of practices at national level for this approach. These data will assist in the development of clinical trials in situations that appear to be most promising in clinical practice.

开始日期2016-02-03

申办/合作机构

Fédération Francophone de la Cancérologie Digestive

NCT02110953 / Terminated临床1期IIT

Phase I Study of Drug-Eluting Irinotecan Beads (DEBIRI) in Refractory Metastatic Colorectal Cancer With Liver-Only or Liver-Predominant Disease

This phase I trial studies the side effects and best dose of irinotecan-eluting beads in treating patients with colon or rectal cancer that has spread to the liver and does not respond to treatment with standard therapy. Irinotecan-eluting beads are tiny beads that have been loaded with irinotecan hydrochloride, a chemotherapy drug. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. This treatment delivers the chemotherapy directly to the tumor area inside the liver instead of to the whole body as with systemic delivery of the drug. Irinotecan-eluting beads may work better that standard chemotherapy in treating patients with colon or rectal cancer that has spread to the liver.

开始日期2016-01-29

申办/合作机构

The Fox Chase Cancer Center

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100 项与 Irinotecan-eluting beads 相关的专利（医药）

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项与 Irinotecan-eluting beads 相关的文献（医药）

2024-08-01·JACC-Heart Failure

Natriuretic Peptides, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction

Article

作者: McMurray, John JV. ; Mc Causland, Finnian R ; Pfeffer, Marc A ; Myhre, Peder ; Neuen, Brendon L. ; Claggett, Brian L. ; McMurray, John J.V. ; Solomon, Scott D ; Zile, Michael R. ; Claggett, Brian L ; Beldhuis, Iris ; Desai, Akshay S. ; Zile, Michael R ; Solomon, Scott D. ; McMurray, John J V ; McGrath, Martina ; Neuen, Brendon L ; Vaduganathan, Muthiah ; Anand, Inder ; Skali, Hicham ; Pfeffer, Marc A. ; Mc Causland, Finnian R. ; Desai, Akshay S

BACKGROUND:

N-terminal pro-B-type natriuretic peptides (NT-proBNPs) are guideline-recommended biomarkers for risk stratification in patients with heart failure. However, NT-proBNP levels are often elevated in chronic kidney disease, introducing uncertainty about their prognostic relevance in persons across a broad range of estimated glomerular filtration rate (eGFR).

OBJECTIVES:

The aim of this study was to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function.

METHODS:

A pooled analysis was conducted of participants with NT-proBNP and eGFR measured at baseline in the I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction), TOPCAT (Americas region) (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function), PARAGON (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction), and DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) trials. The relationship between NT-proBNP and eGFR was assessed using piecewise linear regression. Using multivariable Cox and Poisson regression models, the association of NT-proBNP with outcomes across a range of eGFR was evaluated. The primary outcome was hospitalization for heart failure or cardiovascular death.

RESULTS:

Among 14,831 participants (mean age: 72.1 years; 50.3% female; mean eGFR: 63.3 mL/min/1.73 m², and median NT-proBNP: 840 pg/mL) followed up for a median 33.5 months, there were 3,092 primary outcomes. NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73 m² lower eGFR in patients with baseline eGFR ≥60, 45-<60, and <45 mL/min/1.73 m², respectively (P for nonlinearity < 0.001). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR: 1.37; 95% CI: 1.34-1.41), consistent across different eGFR categories (P for interaction = 0.42). For the same incidence of the primary outcome, NT-proBNP levels were approximately 2.5- to 3.5-fold lower in patients with eGFR <45 mL/min/1.73 m², compared with patients with eGFR ≥60 mL/min/1.73 m². Similar patterns were observed across all outcomes studied, including cardiovascular and noncardiovascular death.

CONCLUSIONS:

The same NT-proBNP concentration predicts a substantially higher absolute risk of adverse outcomes for people with heart failure and reduced kidney function, compared with those with preserved kidney function. These data call into question proposals for higher NT-proBNP references ranges in people with CKD, and suggest that reduced kidney function per se should not be a reason to disregard higher NT-proBNP levels.

2024-05-01·European journal of heart failure

Effects of sacubitril/valsartan according to polypharmacy status in PARAGON‐HF

Article

作者: McMurray, John J.V. ; Vardeny, Orly ; Claggett, Brian L. ; Vaduganathan, Muthiah ; Zile, Michael R. ; Desai, Akshay S. ; Rouleau, Jean L. ; Matsumoto, Shingo ; Yang, Mingming ; Shen, Li ; Solomon, Scott D. ; Jhund, Pardeep S. ; Henderson, Alasdair ; Lefkowitz, Martin

Aims:

Patients with heart failure (HF) and preserved ejection fraction (HFpEF) have a particularly high prevalence of comorbidities, often necessitating treatment with many medications. The aim of this study was to evaluate the association between polypharmacy status and outcomes in PARAGON‐HF.

Methods and results:

In this post hoc analysis, baseline medication status was available in 4793 of 4796 patients included in the primary analysis of PARAGON‐HF. The effects of sacubitril/valsartan, compared with valsartan, were assessed according to the number of medications at baseline: 683 non‐polypharmacy (<5 medications); 2750 polypharmacy (5–9 medications), and 1360 hyper‐polypharmacy (≥10 medications). The primary outcome was total HF hospitalizations and cardiovascular deaths. Patients with hyper‐polypharmacy were older, had more severe limitations due to HF (worse New York Heart Association class and Kansas City Cardiomyopathy Questionnaire scores), and had greater comorbidity. The non‐adjusted risk of the primary outcome was significantly higher in patients taking more medications, and similar trends were seen for HF hospitalization and cardiovascular and all‐cause death. The effect of sacubitril/valsartan versus valsartan on the primary outcome from the lowest to highest polypharmacy category was (as a rate ratio): 1.19 (0.76–1.85), 0.94 (0.77–1.15), and 0.77 (0.61–0.96) (pinteraction = 0.16). Treatment‐related adverse events were more common in patients in the higher polypharmacy categories but not more common with sacubitril/valsartan, versus valsartan, in any polypharmacy category.

Conclusions:

Polypharmacy is very common in patients with HFpEF, and those with polypharmacy have worse clinical status and a higher rate of non‐fatal and fatal outcomes. The benefit of sacubitril/valsartan was not diminished in patients taking a larger number of medications at baseline.

2023-12-06·Cureus

Drug-Eluting Bead, Irinotecan (DEBIRI) Therapy for Refractory Colorectal Liver Metastasis: A Systematic Review

Review

作者: Fatima, Umaima ; Osman, Hafsa A ; Gonzalez, Natalie A ; Sheikh, Aaiyat ; Puvvada, Chaitanya S ; Haridi, Merna ; Soomro, Faiza H ; Dayo, Sana M ; Yu, Ann Kashmer

Colorectal cancer and related mortality present a profound challenge in its management, even in this modern age. Even today, colorectal cancer-related deaths rank third in the world. Despite having multiple lines of chemotherapy, combined with radiotherapy and chemoembolization techniques, after or before surgical resection, the five-year survival rate is approximately 20%. Drug-eluting bead, irinotecan (DEBIRI) is a new technique that involves embolization of the feeding vessels to the tumour and delivering irinotecan for its chemotherapeutic effects. A significant amount of literature compares DEBIRI as an adjunct to various lines of chemotherapy. However, so far, not much data are available on DEBIRI as a singular treatment for those patients who have had multiple chemotherapies and still progressing and are not fit for liver resection. In this systematic review, we aim to highlight and bring together the results of those studies that focused on this specific patient group. A systematic search of the literature involving three large databases (published between January 2017 and July 2022), excluding languages other than English, was conducted to identify articles documenting patients who had disease progression despite chemotherapy and were not fit for surgical resection. The level of evidence and the quality check were assessed by two independent reviewers, and consensus with the senior author resolved disagreements. Out of seven studies that met the final criteria, we found a pooled cohort of 302 patients. The mean age of the patients was 61.2 years, ranging from 40.7 to 84 years. The most commonly used DEBIRI beads were M1 (70-150 um) and M2 (100-300 um), but two studies reported the use of 40 um as well. The total number of DEBIRI treatments performed in our pooled cohort was 904. The majority of the studies reported only G1/G2 toxicities among the patients, with maximal toxicity of G4 in a few selected patients. The median overall survival in our pooled cohort was 19.52 months. The median progression-free survival in our data was 5.76 months. Our systematic review concludes that DEBIRI is undoubtedly a useful treatment modality with an acceptable toxicity profile. This treatment offers a good overall survival benefit for refractory colorectal liver metastasis.

项与 Irinotecan-eluting beads 相关的新闻（医药）

2024-09-02

·药融圈

潜力靶点深加工：主打长效“初生牛犊”Spyre Therapeutics，市值超百亿人民币

▲10月26-27日成都中国临床试验产业发展大会免费报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。药融圈之前和大家分享了Paragon Therapeutics孵化的第一家Biotech——ApogeeTherapeutics（相关阅读：自免高热赛道“毛头小司”，一年股价涨幅曾超300%：主打长效），今天想与大家一起聊聊其孵化的第二家公司——Spyre Therapeutics。值得一提的是，虽然Paragon Therapeutics是投资机构Fairmount在2021年才创立的，但是截止2024年8月底，其已经成功孵化了四家公司，其采取的策略简单粗暴，直接针对成熟靶点开发迭代的长效抗体药物，技术上也多采用专利过期的YTE改造策略。不得不说，直到目前为止，从孵化公司的融资情况来看该策略还是比较奏效。药融云数据，www.pharnexcloud.com：公司信息从药融云数据库获悉，Spyre Therapeutics的成立时间可以追溯到2013年（具体缘由下面会分享），目前主要专注于开发炎症性肠病的新型单克隆抗体。Spyre Therapeutics可以说是成立于2013年底的Aeglea BioTherapeutics（专注于开发罕见代谢疾病）的救司手段，2023年6月，Aeglea宣布以换股交易的方式收购Spyre Therapeucs，交易完成后，Aeglea BioTherapeutics的股东拥有合并后公司约5.5%的股份，新公司由Aeglea和Spyre高管共同领导。在此交易之前，Aeglea BioTherapeutics正在经历临床失利和濒临破产的情况，股价从高位下跌超过95%，于是公司只得大量裁员。药融云数据库：融资信息合并后公司便将之前的针对罕见代谢疾病精氨酸酶1缺乏症的pegzilarginase的全球权利出售给了 Immedica Pharma，也算是正式表示其专注炎症性肠病的决心。随后公司宣布更名为Spyre Therapeucs，股价连续大涨，且在2023年和2024年分别完成了一笔1.8亿美元的融资（总计3.6亿美元）。当前研发管线主打长效 Spyre Therapeutics的管线主要专注于炎症性肠病（IBD），IBD是一种以胃肠道炎症为特征的慢性疾病，包括溃疡性结肠炎（UC）和克罗恩病（CD）两种主要疾病。在研管线中SPY001、SPY002和SPY003均采用半衰期延长工程技术设计，SPY004则是与上述几条管线不同作用机制的单克隆抗体。目前各管线具体进展情况如下： 01 SPY001 药融云数据，www.pharnexcloud.com显示：SPY001是一种研究性新型皮下延长半衰期单克隆抗体，专为高浓度配制，可最大限度地提高诱导暴露和潜在缓解率，并实现不频繁的皮下维持给药，主要靶向整合素α4β7。整合素作为一类重要的细胞表面粘附分子，是直接介导白细胞迁移运动的重要蛋白，与炎症反应关系密切。整合素α4β7主要表达在淋巴细胞表面，负责介导淋巴细胞从血液循环进入肠道和中枢神经系统，其功能的异常与人类自身免疫疾病密切相关，如溃疡性结肠炎、克罗恩病等。在头对头的临床前研究中，SPY001在阻断MadCAM-1粘附方面显示出与vedolizumab（注射用维得利珠单抗）相当的效力，并且显示出明显更长的半衰期，有可能每两三个月才需要给药一次。 2024年6月18日，Spyre Therapeutics宣布已开始SPY001的临床试验1期研究，该临床试验1期研究是一项针对健康志愿者的双盲、安慰剂对照试验，预计将招募48名健康志愿者，包括至少四个单次递增剂量（SAD）队列和两个多次递增剂量（MAD）队列，主要终点是安全性，次要终点是药代动力学。预计该研究的中期安全性和药代动力学数据会在2024年年底前公布，并且在等待临床试验1期研究的数据之前，公司可能会在2025年开始该管线的临床试验2期研究。前面提到的注射用维得利珠单抗是武田制药的重磅IBD治疗药物，可特异性地抑制MAdCAM-1与α4β7整合素的结合，从而阻止免疫细胞定向迁移到肠道黏膜，缓解炎症性肠病的症状。2014年在美国和欧洲上市以来销售增长强劲，是武田最畅销的产品之一。截图自：武田财报从武田2023年4月~2024年3月的财年年报来看，消化道是公司营收的主要来源，Entyvio（注射用维得利珠单抗）作为消化道产品管线的支柱产品，全年营收8009亿日元（约合美元55亿），占公司合并收入的19%。 02 SPY002 阻断TL1A与其同源受体DR3的相互作用已被证明可以改善CD和UC患者的疾病进程。SPY002是一种靶向TL1A的新型延长半衰期的全人lgG1单抗，对TL1A各种亚型都具有亚纳摩亲和力，可以有效抑制TL1A介导的信号传导。 2024年2月，Spyre Therapeutics在第19届年度ECCO大会上公布了SPY002主要开发候选药物的临床前数据，证明了其在非人灵长类动物（NHP）中的亚纳摩尔结合亲和力和效力，以及24天的药代动力学半衰期，与临床阶段的抗TL1A相比增加了两到三倍。预计在2024年下半年开始对两个SPY002候选药物进行FIH（首次人体试验），2025年上半年获得健康志愿者的中期数据。如果成功，公司预计一个SPY002候选药物将进入进一步的临床开发。 2023年4月，默克通过以108亿美元的价格收购了自免公司Prometheus Biosciences，以进军免疫疾病治疗市场，通过该收购也获得了靶向TL1A的药物——MK-7240，此外，Roivant Sciences（RVT-3101）和梯瓦制药（TEV-48574）也在加紧自家管线的研发进程。与上述三种临床阶段的管线相比，SPY002在NHP中的半衰期延长，也具有不需要频繁通过皮下给药的优势。 03 SPY003 SPY003是一种靶向IL-23的p19亚基的高效选择性的研究性单克隆抗体。预计在2024年下半年启动IND赋能研究，并于2025年上半年启动FIH试验。值得一提的是，IL-23也是艾伯维的Skyrizi（利生奇珠单抗）和强生公司的Tremfya（古塞奇尤单抗）靶向的蛋白质。基于现有优质管线开展联合用药 α4β7抑制是胃肠病学家首选的一线治疗选择，因为它具有良好的安全性和肠道选择性作用机制，并且在VARSITY研究中显示出优于TNF抑制的疗效，Deanna Nguyen博士（Spyre Therapeutics临床开发高级副总裁）表示这种独特的安全性和有效性特征，结合更方便的给药频率，可以使SPY001成为IBD联合治疗的理想骨干，同时抑制其他高活性机制，包括T1LA和IL-23。注：VARSITY研究是武田开展的一项随机双盲双模拟全球多中心的临床试验3b期研究，旨在比较维多珠单抗（静脉注射）与阿达木单抗（皮下注射）在治疗中度-重度活动性溃疡性结肠炎患者中，在第52周时的有效性与安全性。根据最近关于与第三方产品联合疗法治疗IBD的研究结果，公司目前正在开展下一代单克隆抗体的联合治疗研究，目前正在临床前研究的联合疗法包括：（1）SPY120：SPY001和SPY002联合；（2）SPY130：SPY001和SPY003联合；（3）SPY230：SPY002和SPY003联合。财务状况 2023年度Spyre Therapeutics研发费用为8950万美元，而上年同期只有5858万美元，这一增长主要与公司IBD产品线的临床前开发和生产费用的增加有关；一般和行政费用为3995万美元，上年同期为2853万美元；其他费用为9651万美元；2023年度净亏损6320万美元。 2024年上半年研发费用为6760万美元；一般和行政费用2440万美元；其他收入930万美元；净亏损8270万美元。分季度来看，2024年第二季度研发费用总额为3260万美元，上年同期为1740万美元，这一增长是由公司IBD产品线的临床前和临床开发和生产费用推动的，部分被与公司传统罕见病产品线相关的费用减少以及Paragon Therapeutics与SPY003开发成本相关的非经常性损益所抵消。一般和行政费用总额为1150万美元，上年同期为1210万美元。其他收入共计530万美元，主要受公司现金和有价证券所赚取的利息推动。净亏损3880万美元，而上年同期则高达2.171亿美元。截至2024年6月30日，Spyre Therapeutics的可用现金和现金等价物、有价证券和限制性现金为4.263亿美元，当前的资金状况预计将足以支持公司继续运营到2027年。截止2024年8月26日，Spyre Therapeutics公司市值13.71亿美元。8月30日，收盘市值为14.60亿美元。参考： NMPA/CDE；药融云数据，www.pharnexcloud.com； FDA/EMA/PMDA；相关公司公开披露（除标注外，正文图片均来自企业官网）； https://spyre.com/； https://mp.weixin.qq.com/s/qkg1Cd55pgHvqPGJVORKwQ； https://mp.weixin.qq.com/s/rKoixewPMhk32GT0Z2Ab2A； https://assets-dam.takeda.com/image/upload/Global/Investor/ASR/Y2023/E_FY23_ASR.pdf； https://www.medsci.cn/article/show_article.do?id=29ed18026114； https://mp.weixin.qq.com/s/8d_bNiG15Q_HySJJDEugeQ；等等。本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

并购

2024-03-16

·药智网

成立2年、市值40亿美元，一场有预谋的“生物科技实验”

成立仅7个月，顺利IPO；资本寒冬，IPO超募3亿美元；上市仅9个月，股价涨幅311%，市值达到40亿美元。你很难想象，这些战绩，都是一家核心管线均处于临床前biotech，Apogee创造的。当然，一切并非毫无迹象可循。癌症之外，市场对于自免热度极高。近两年，大额并购案不断，度普利尤单抗的持续进击，更是刺激着市场的神经。而Apogee要做的，则是挑战甚至超越度普利尤单抗。作为一家开发炎症和免疫学（I&I）适应症差异化疗法的biotech，Apogee核心管线有二，APG777和APG808。前者是一款延长半衰期的长效IL-13抗体，用于治疗特应性皮炎（AD），后者则是一款延长半衰期的畅销IL-4Ra抗体，用于治疗慢性阻塞性肺病(COPD)。由于APG808尚未进入临床，因此，市场当前的热情核心是源于APG777的潜力。在临床前研究中，APG777表现出与另一种IL-13药物（礼来的Lebrikizumab）“相当或优于”IL-13抑制作用，且半衰期明显更长，预计给药间隔可能是每两个月或每三个月。而度普利尤单抗需要每两周给药一次。而最新的1期研究的结果，超过了APG777的预期，其将加速二期临床，并探索3个月到6个月注射一次的治疗方案。APG777展露出优于当前同靶点药物甚至是IL-4Rα单抗的潜力，Apogee甚至称其能够成为未来500亿美元AD市场的领导者。基于此，尽管仍处于临床早期，但市场已将预期打满。那么，Apogee能撑起市场的期待吗？012年40亿美元Apogee成立于2022年，是Paragon Therapeutics拆分出的第一家公司。2022年12月7日，Apogee宣布完成1.69亿美元B轮融资。根据Apogee官网公布的信息，目前公司拥有四条具有数十亿美元潜力的管线，适应症集中于AD、COPD、哮喘等相关I&I领域。其中，APG777和APG808为核心管线。半年后，Apogee成功在美国完成IPO上市。尽管市场寒冬依旧，但Apogee依旧完成了超募，募资3亿美元，仅次于去年5月上市的Acelyrin（IPO募资额达5.4亿美元）。上市首日，公司股价首日暴涨24.88%。无论是IPO发行规模，还是首日涨幅，均显示出市场对Apogee的超高热情，然而，Apogee仅仅成立7个月时间，核心管线尚未正式进入临床阶段。如果算上IPO募资，意味着Apogee在成立半年多的时间，便累计获得了3.69亿美元的融资。这还是在市场下行、资本寒冬之中完成的。这样的成绩，对于绝大多数苦于寒冬融资无门的biotech，绝对是不敢想象的事情。那么，为什么Apogee获得资本市场的追捧？这背后是市场对于自免潜在重磅药物的追捧。2022年12月，辉瑞与Roivant Sciences宣布成立Telavant，专注于TL1A单抗RVT-3101的开发和商业化；12月，武田以60亿美元的价格从Nimbus Therapeutics收购口服的选择性变构酪氨酸激酶2（TYK2）抑制剂NDI-034858；2023年4月，默沙东以118亿美元收购Prometheus Biosciences，获得了TL1A资产；6月，礼来以24亿美元收购DICE Therapeutics；10月，罗氏以71亿美元收购Telavant，获得后者重磅核心产品溃疡性结肠炎候选治疗药物RVT-3101……在海外，自身免疫疾病药物市场一直是药王储备池。尽管老药王修美乐在专利悬崖之下，销量一路下滑，但度普利尤单抗等后来者的快速崛起，依旧让市场对自免领域充满想象。2023年底，Nature杂志子刊发布《TOP product forecasts for 2024》预测了2024年销售额排名TOP10的产品，修美乐掉出前十，度普利尤单抗预计将进入前三甲。2023年，度普利尤单抗销售额达到115.7亿美元，支撑度普利尤单抗销售额的一个重要适应症，便是特应性皮炎。今年，度普利尤单抗还有不少新适应症里程碑事件，未来其销售额天花板值得遐想。而Apogee要做的便是挑战甚至超越度普利尤单抗。02瞄准自免痛点度普利尤单抗的吸金力度之大，让后来者们蠢蠢欲动，特应性皮炎也成为了药企的必争之地。一来，这一市场患者规模庞大；二来，由于特应性皮炎致病机制尚未完全清晰，因此无法治愈，患者需要长期用药。最重要的是，由于现有药物普遍都有较大的副作用，或是依从性不高，如度普利尤单抗需要每两周给药一次，这使得，对特应性皮炎的治疗存在着极大的临床未满足需求。Apogee则瞄准这一痛点，其核心管线主打长效半衰期。这对于需要长期用药的自免患者，无疑是一大吸引力。其当前进展最快的管线，即意在挑战礼来Lebrikizumab、赛诺菲度普利尤单抗的重磅竞争对手APG777。与Lebrikizumab一样，APG777靶向IL-13细胞因子。在免疫系统异常炎症假说中，异常炎症，是指由于各种因素导致的患者皮肤屏障受损，患者接触过敏原后，被激活的由2型辅助性T细胞驱动异常免疫应答。理论上，阻断IL-4和IL-13这两个给Ⅱ型免疫反应通风报信的调节因子，能阻断Th2炎症的中枢通路，抑制过强的免疫反应。IL-13和IL-4作为配体，要和相应受体结合才能发挥功能。度普利尤单抗的机制是用IL-4Rα抗体与IL-4Rα结合，IL-13和IL-4自然无从与受体结合。而APG777则被设计为结合IL-13，从而通过阻止IL-13Rα1/IL-4Rα异二聚体的形成来破坏Th2信号传导。其独特之处在于，通过YTE突变优化抗体结构，使药物半衰期和给药周期大幅度延长，提高患者的用药依从性。APG777在片段可结晶（Fc）区含有三重氨基酸修饰，通常为M252Y/S254T/T256E（即“YTE”突变），旨在通过在酸性pH条件下增加与新生儿Fc受体（FcRn）的结合来延长其在非人灵长类动物和人类中的半衰期。临床前数据显示，APG777在抑制IL-13信号传导方面与礼来的Lebrikizumab有相同或更好的效力，且半衰期更长。预计APG777的人类半衰期约为80至110天。这样的研究数据，支持APG777每两个月一次的维持给药计划。因为许多AD患者会经历“针头疲劳”，尤其是儿科患者经常害怕针头，每两三个月给药一次，将会增加患者的用药依从性。这可能会为中度至重度AD患者护理标准，带来潜在的变革性变化。也正是基于这一预期，Apogee倍受资本追捧。临床前的优秀表现延续至一期临床，甚至大超Apogee预期。数据显示，APG777能够抑制AD关键生物标志物pSTAT6和TARC持续3个月以上；与IL-13类药物拥有类似的安全性，相比IL-4Rα单抗结膜炎发生率低、止痒方面表现不错；超长的半衰期，二期临床将探索3个月到6个月注射一次的治疗方案。Lebrikizumab在特应性皮炎的临床效果已经堪称优秀，相比度普利尤单抗用药方式更长效（四周一次）且安全性也更具优势，而APG777则展现出更优的潜力。3到6个月意味着，APG777每年仅需2-4次注射，而当前治疗范式为每年12-26次注射。如果能够继续保持，无疑将极大提升患者依从性。这一结果发布后，Apogee股价暴涨42%，目前总市值已达40亿美元。03一套行之有效的打法不止APG777，Apogee其他管线也主打长效。比如APG808。这是一种靶向IL-4Ra的延长半衰期单抗，用于治疗COPD。在头对头临床前试验中，已经证明，APG808在抑制IL-4Rα信号传导方面，与度普利尤单抗相同或更好的效力。此外，根据临床前研究，APG808可以每六周或每两个月维持给药一次，而第一代IL-4Rα抗体每两周给药一次，APG808将带来显著的改进。Apogee的第三个项目APG990是一种针对OX40L的延长半衰期单抗，同样用于治疗AD。虽然该靶点在肿瘤适应症研发方面遭遇挫折，但OX40或其配体OX40L的抗体一直是全球自免领域的研发热门方向。随着安进、赛诺菲的OX-40抗体的突破，竞争更是白热化。Apogee第四个项目APG222，是针对IL-13和OX40L的潜在联合疗法用于特应性皮炎。可以看到，Apogee的核心管线主打的就是半衰期延长，且围绕自免领域的热门靶点做了多重布局。除此之外，Apogee也希望不断扩大药物的适应症。比如针对APG777，Apogee表示可能会在2025年启动一项针对哮喘的2期试验，以进一步评估开发APG777用于其他I&I适应症的机会，包括斑秃、鼻窦炎、慢性自发性荨麻疹、嗜酸性粒细胞性食管炎和结节性痒疹等。表面来看，Apogee获得市场追捧，是基于其核心管线的巨大潜力。但更进一步来看，这更像是由Paragon背后的投资机构发起的，一场有预谋的“生物科技实验”。Paragon是由Fairmount Funds创办，Apogee创始股东也包括了Fairmount和Venrock两家机构。正如前文所说，Apogee是从Paragon拆分出来的第一家公司，Spyre Therapeutics则是Paragon拆出来的第二家公司。从管线策略来看，Spyre与Apogee极其相似。Spyre核心管线为针对炎性肠炎（IBD）的长效抗体，SPY001和SPY002预计2024年进入临床研究阶段。其中，SYP001的靶点为α4β7，即武田的重磅IBD药物维得利珠单抗的靶点。Spyre表示，相比维得利珠单抗目前是每两周一次给药，SYP001的目标是达到每两个月或每季度给药。SPY002则靶向重磅交易不断的TL1A。去年，默沙东和罗氏先后斥巨资收购相关管线。Spyre对SYP002同样充满信心。从资本市场表现来看，Spyre先Apogee一步完成借壳上市。去年6月，Aeglea宣布以换股交易的方式收购Spyre。尽管均处于临床前，但Spyre的管线同样吸引了大量投资者。Aeglea与PIPE投资（私募基金）达成无投票权可转换优先股的最终协议，筹集到2.1亿美元。这些资金将用于推进Spyre潜在同类最佳的IBD产品组合并支持运营，直至2026年。而自2023年11月至今，Spyre股价涨幅超过270%，最新市值达16亿美元。换句话说，在资本市场表现层面，Spyre与Apogee同样优秀。在资本情绪高涨时期，大部分管线仅处于I期临床阶段，甚至更早期的biotech也能完成上市融资。但如今的环境，市场更追求确定性。Spyre、Apogee却靠着临床前管线，迅速完成融资、上市。Paragon似乎形成了一套行之有效的路径，旗下公司所选择的领域，存在着巨大的未被满足的临床需求，均主打长效针对市场痛点，完美契合了市场对于自免潜在重磅药物的追捧。当然，一切还要靠数据说话。在自免这一大风口上，Apogee并非被吹得最高的那一个。去年5年，自身免疫新药公司Acelyrin以5.4亿美元融资，高调完成IPO上市，成为2023年美股IPO规模最大的生物医药企业，上市首日同样大涨30%。但随着其核心管线在治疗中度至重度化脓性汗腺炎的IIb/III期试验中失败，Acelyrin又回到了现实。如今，Acelyrin市值仅8亿美元。去年一年其股价较IPO发行价跌去56%，成为年内表现最差的生物医药新股。相比之下，Apogee已经用一期数据证明了其临床前数据的可延续性，也获得了市场的大力追捧；Spyre则还处于自证阶段。尽管早期数据亮眼，后期翻车的故事屡见不鲜，但华尔街大佬们愿意加入这场豪赌。注：以上图片来源氨基观察来源 | 氨基观察（药智网获取授权转载）撰稿 | 武月责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

IPO免疫疗法临床2期

2023-12-04

·FierceHealthcare

Reaching the summit of healthcare, one step at a time

None By Marcus Perez, President, Altera Digital Health The end of the year is always a time for reflection, and looking back on 2023, it’s clear that job satisfaction and burnout remain industry-wide issues. So, where do we go from here? And how do we make that happen? Altera Digital Health aims to bring next-level healthcare within reach through sustainable progress. The core values of our parent company, Harris Healthcare, provide a blueprint to achieve that. One of those values is “Solutions, Not Problems.” Here’s where Altera is putting its time, energy and attention to create much needed, lasting change. Enhancing usability When EHRs first hit the market, there was a lot of hype around how they would transform healthcare. Incentives were created to accelerate adoption (i.e., the HITECH Act), and we’ve been pretty successful in that regard. But going from paper charts to EHRs was only the first step. As usage grew, unintended consequences emerged. Research in the Journal of the American Medical Informatics Association (JAMIA) found high levels of burnout correlate to high levels of EHR stress. Equally troubling, a study in the Journal of the American Medical Association (JAMA) suggests poor EHR usability is associated with poor EHR safety performance. Confronted with this reality, Altera leaned into another one of our values: “Understanding and Learning.” In order to build positive experiences with our products, we knew we needed to better understand providers’ daily lives and learn what did and didn’t fit into their workflows. We achieved (and continue to do) this by ensuring that, at every step in the design process, clinicians and our design, development and engineering teams identify problems and work together to identify new possibilities. This enables us to build products that support, rather than disrupt, the way providers work. Advancing interoperability Additional byproducts of EHR adoption include the data-sharing challenges that emerged. It is not uncommon for patients to seek care at different healthcare organizations, and these organizations may use different vendor systems. Even within individual organizations, different departments using different versions of the same EHR are often unable to exchange complete medical records. No matter the circumstances, making care decisions without access to comprehensive patient histories is frustrating at best and harmful at worst. While much progress has been made, there is room for improvement. Approximately 62% of non-federal acute care hospitals in the U.S. are able to send, receive, find and integrate summary of care records into EHRs. Until that figure reaches 100%, patients and providers will deal with the consequences. This brings us to another core value: “Communicate and Share Knowledge.” Having the right information in the right place at the right time is table stakes in our industry, and it is not limited to patient care delivery itself. For example, as more healthcare organizations transition to value-based care models, interoperability will be crucial to care coordination among different providers and accurate reimbursement for services rendered. Altera has a history of supporting information-sharing, and we continue to embrace it, leveraging current interoperability standards like FHIR to enable easier extraction and consumption of data between solutions. Additionally, our award-winning interoperability platform, dbMotion™ Solution, takes things a step further, enabling a high level of information exchange among disparate EHR systems. Improving incrementally Bettering usability and interoperability across Altera’s portfolio converges into our larger aim to continually improve our core products, including Sunrise™, Paragon® and TouchWorks® EHR. Many health IT organizations get caught up in “shiny object syndrome,” always chasing the next innovation they claim will revolutionize healthcare, overlooking existing products in the process. Altera is taking an alternative approach. Make no mistake, we are always working to bring new digital enhancements to our clients. We want our solutions to serve as valuable assets and springboards for further innovation. Our ultimate priority, however, is to be a little better for our clients every day. This is best represented by the core value of, “Discipline. Unwavering and Relentless Focus.” Altera is constantly soliciting client feedback, making changes on a monthly basis to strengthen our products and align them even more closely to clinician workflows. That means making meaningful yet management advancements that benefit our clients and their patients today. Onward and upward Altera’s efforts to advance usability and interoperability through incremental improvements get at the heart of another core value: “Empowerment at the Point of Contact.” From the point of care to the billing office, we know healthcare can be so much better. It should be easier to access, understand and navigate for everyone involved. A new era of healthcare has begun, and we’re not looking back.

AHA会议

100 项与 Irinotecan-eluting beads 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
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研发状态

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适应症	国家/地区	公司	日期
胆管癌	-	Singapore General Hospital Pte Ltd.	-
结直肠癌	-	Singapore General Hospital Pte Ltd.	-
胶质瘤	-	Singapore General Hospital Pte Ltd.	-
肝癌	-	Singapore General Hospital Pte Ltd.	-

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01839877 (FFCD-1201 \| FFCD 1201, CTgov)	临床2期	结肠癌肝转移	58	systemic FOLFOX+DEBIRI	憲壓壓廠糧壓衊選鹹廠(範積衊鏇廠顧觸艱願網) = 襯齋餘製鏇顧廠憲範糧艱蓋繭鑰襯顧窪襯壓製 (壓夢糧鏇鹽鏇鏇艱製顧, 鹹夢夢繭衊鏇衊積鬱艱 ~ 淵積鹹淵憲糧鏇夢遞鑰) 更多	-	2024-10-08
ASCO2023	N/A	结直肠癌肝转移	101	Irinotecan-eluting HepaSphere chemoembolization plus HAIC	憲築鏇鹽鏇壓網鹹壓鏇(膚襯鏇築觸積淵窪窪蓋) = 27.7% 蓋窪餘衊獵膚繭廠願餘 (遞製築醖簾鑰選範蓋淵 ) 更多	积极	2023-05-31
ASCO_GI2023	N/A	不可切除的肝细胞癌	208	DEB-ICI group	鬱憲齋獵選積鏇鹽獵積(夢齋餘憲遞簾願衊獵願) = 窪顧網繭襯淵夢鹽遞鑰餘淵蓋衊網繭蓋積簾艱 (範壓鹹糧範憲壓鑰醖獵 )	-	2023-01-24
ASCO_GI2023	N/A	不可切除的肝细胞癌	208	DEB group	鬱憲齋獵選積鏇鹽獵積(夢齋餘憲遞簾願衊獵願) = 壓醖顧蓋願鹹衊鏇衊選餘淵蓋衊網繭蓋積簾艱 (範壓鹹糧範憲壓鑰醖獵 )	-	2023-01-24
NCT01285102 (CTgov)	临床1期	粘液腺癌 \| 印戒细胞癌 \| 复发性结肠癌 ... 更多	4	irinotecan	壓觸艱繭襯鏇廠鏇醖淵(鏇構製範壓鹽繭衊簾築) = 膚願窪餘窪夢淵鹽蓋遞鹹網獵築鏇範築糧鹽獵 (壓構鹽繭願壓網鑰簾艱, 齋鑰繭淵淵鹽鬱網憲鹹 ~ 鏇鹹齋積範構鏇顧製衊) 更多	-	2021-12-20
NCT03007225 (treatment of HCC, CTgov)	临床4期	肝细胞癌	50	Doxorubicin hydrochloride (Group 1)	簾餘製膚夢構顧鹹齋膚(窪範觸廠構衊襯壓壓壓) = 鏇憲壓鹽鬱獵選鬱醖積窪廠窪選淵獵鏇衊鬱夢 (構獵願廠繭繭衊窪觸鹹, 構膚夢選獵糧築衊積齋 ~ 網積網襯遞觸製簾築憲) 更多	-	2020-09-17
NCT03007225 (treatment of HCC, CTgov)	临床4期	肝细胞癌	50	Urografin+gentamycin+Doxorubicin hydrochloride+Lipiodol (Group 2)	簾餘製膚夢構顧鹹齋膚(窪範觸廠構衊襯壓壓壓) = 壓範窪齋觸壓構觸淵鹹窪廠窪選淵獵鏇衊鬱夢 (構獵願廠繭繭衊窪觸鹹, 顧窪顧鏇簾襯窪積糧顧 ~ 遞襯膚選膚夢鹹積膚齋) 更多	-	2020-09-17
NCT01839877 (FFCD-1201, Pubmed \| Med J Aust)	临床2期	结直肠癌肝转移一线	58	DEBIRI plus mFOLFOX6	憲製壓壓廠衊鏇築廠醖(獵襯窪淵鑰積鑰網範構) = 憲齋鑰醖顧憲鏇製憲鏇壓鬱鬱淵鑰顧膚艱襯簾 (襯壓壓遞選願積遞糧夢 ) 更多	-	2020-06-08
NCT02015754 (CTgov)	临床2期	结直肠癌肝转移	14	TACE+DEBIRI	選餘製糧鏇繭壓範襯淵(艱獵窪顧製積鹽夢鬱廠) = 襯蓋簾願壓憲廠顧膚網網蓋憲遞願艱鏇壓願觸 (顧鹹願遞艱鑰構蓋壓窪, 夢構範網醖鹹鑰選製齋 ~ 觸鑰網鏇醖壓築構顧網) 更多	-	2018-03-22
ASCO_GI2015	临床2期	结直肠癌肝转移	-	DEBIRI	鑰糧齋淵窪鑰醖遞製鏇(壓範築窪網選夢憲獵鏇) = 築衊齋夢艱願鹽鑰鹽餘繭艱製鹹餘選範齋繭願 (遞願鏇鹹願製鏇壓膚糧 ) 更多	积极	2015-01-20
ASCO2013	N/A	不能切除的大肠癌	10	IAIRIM	餘獵範廠餘襯範鹹艱蓋(齋選廠鏇積網遞築憲積) = 構網繭簾齋簾膚觸積鏇齋選壓製糧願膚艱簾鏇 (鏇蓋構願衊襯範簾構衊, 24 ~ 48) 更多	-	2013-05-20
ASCO_GI2013	N/A	结直肠癌肝转移新辅助	10	DEBIRI	廠膚廠築積襯築願窪壓(膚夢觸獵淵築窪鏇鏇築) = 襯艱窪艱鏇齋遞鏇餘鑰選顧願積選壓醖製蓋鹹 (蓋遞構鑰觸鹹顧醖鬱構 ) 更多	-	2013-02-01