The purpose of the study is to evaluate the efficacy and safety of CTX001 (exa-cel) in adolescent and adult participants with severe sickle cell disease (SCD), βS/βC genotype (HbSC).

开始日期2027-07-31

申办/合作机构

Vertex Pharmaceuticals, Inc.

NCT05477563

/ Recruiting临床3期

A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease

This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.

开始日期2022-08-02

申办/合作机构

Vertex Pharmaceuticals, Inc.

NCT05356195

/ Active, not recruiting临床3期

A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent β-Thalassemia

This is a single-dose, open-label study in pediatric participants with TDT. The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001).

开始日期2022-05-03

申办/合作机构

Vertex Pharmaceuticals, Inc.

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100 项与 Exagamglogene Autotemcel 相关的专利（医药）

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项与 Exagamglogene Autotemcel 相关的文献（医药）

2026-12-31·JOURNAL OF MEDICAL ECONOMICS

Article

作者: Udeze, Chuka ; Fang, Honghao ; Gargano, Michael ; Lopez, Andrea ; Ogunsile, Foluso Joy ; Jeyakumar, Sushanth ; Li, Nanxin ; Yang, Hongbo

AIMS:

Exagamglogene autotemcel (exa-cel) is a one-time nonviral gene-edited therapy approved in the United States (US) for treatment of patients aged ≥12 with transfusion-dependent β-thalassemia (TDT). Standard of care (SOC) for TDT includes regular red blood cell transfusions (RBCTs) and iron chelation therapy. This study estimated long-term clinical outcomes and cost-effectiveness of exa-cel vs. SOC among patients with TDT in the US.

METHODS:

A Markov model was developed to compare the expected lifetime costs and clinical outcomes of patients with TDT treated with exa-cel compared to SOC from the US payer and societal perspectives. The model structure is based on transfusion status, which impacts iron levels and risk of developing TDT-related complications. The model incorporated data from the phase 3 pivotal CLIMB THAL-111 trial and other inputs from literature. Model outcomes included life years (LYs) and quality-adjusted LYs (QALYs) as well as number of RBCTs and proportion of patients developing complications over a lifetime; costs and incremental cost-effectiveness ratios (ICERs) were also estimated. Costs and outcomes were discounted at 3% annually.

RESULTS:

In the eligible patient population (average age at baseline: 21 years), exa-cel was projected to improve survival by 17.6 years (mean age of death, exa-cel: 64.9 years vs. SOC: 47.3 years), reduce the number of RBCTs received by 425 (exa-cel: 26 vs. SOC: 451), and lower the proportion of patients developing TDT-related complications. Exa-cel was associated with increased discounted costs compared to SOC (exa-cel: $2.9 M vs. SOC: $1.8 M). The ICER per discounted QALY for exa-cel versus SOC was $114,100 from the payer perspective and $55,400 from the societal perspective.

CONCLUSIONS:

Compared to SOC, exa-cel was projected to considerably reduce the number of RBCTs and TDT-related complications, improve survival, and reduce disease-related costs. Exa-cel is projected to be a cost-effective treatment option for patients with TDT in the US.

2026-08-01·AMERICAN JOURNAL OF HEMATOLOGY

Article

作者: Hobbs, William ; Kattamis, Antonis ; Sheth, Sujit ; Meisel, Roland ; Algeri, Mattia ; Lang, Peter ; Corbacioglu, Selim ; Kuo, Kevin H. M. ; Frangoul, Haydar ; Shah, Ami J. ; Cappellini, Maria Domenica ; de la Fuente, Josu ; Chopra, Yogi ; Kirby‐Allen, Melanie ; Li, Amanda M. ; Zairis, Sakellarios ; Liu, Tina ; Rupprecht, Joachim ; Mapara, Markus Y. ; Grupp, Stephan ; Liem, Robert I. ; Locatelli, Franco ; Merkeley, Hayley ; Carpenter, Ben ; Kwiatkowski, Janet L.

ABSTRACT:

Exagamglogene autotemcel (exa‐cel) is a one‐time, ex vivo, CRISPR‐Cas9 gene edited cell therapy approved for patients with transfusion dependent β‐thalassemia (TDT) aged 12–35 years. In a Phase 3 study (CLIMB THAL‐111), exa‐cel treatment resulted in reactivation of fetal hemoglobin and increases in total hemoglobin, leading to transfusion independence in 91% of participants. Here, we report on the impact of exa‐cel treatment on measures of ineffective erythropoiesis and iron homeostasis, which were secondary and exploratory endpoints in CLIMB THAL‐111 and the CLIMB‐131 long‐term follow‐up study. Prior to exa‐cel infusion, all participants were receiving regular red blood cell transfusions and iron chelation therapy. At time of data cut (April 2025), 98% of participants (55 of 56) had been transfusion independent for ≥ 12 months and 38 (68%) had discontinued iron removal therapy (mean duration off iron removal therapy 19.4 months). Following transfusion independence and cessation of iron removal therapy, erythroferrone concentrations decreased and hepcidin levels normalized in all participants, indicating correction of ineffective erythropoiesis and restoration of iron homeostasis. Further supporting this finding, improvements and trends toward normalization were seen in key erythropoiesis biomarkers, including erythropoietin levels, reticulocyte counts, and soluble transferrin receptor concentrations. Iron overload biomarkers, including ferritin, liver iron concentration, and cardiac T2*, decreased and then remained stable throughout follow‐up, even after cessation of iron removal therapy. These results demonstrate restoration of effective erythropoiesis and iron homeostasis after exa‐cel infusion in the setting of transfusion independence following reactivation of fetal hemoglobin. (CLIMB THAL‐111 and CLIMB‐131; Clinical Trials.gov numbers NCT03655678 and NCT04208529).

2026-05-01·Annales Pharmaceutiques Francaises

Analyse de risques selon la méthode AMDEC appliquée au circuit pharmaceutique d’un médicament de thérapie génique ex vivo Casgevy® dans la bêta-thalassémie

Article

作者: Tawil, Stéphanie ; Rascle, Pauline ; Laflotte, Alexia ; Vermersch, Agathe ; Gervaise, Caroline ; Schwiertz, Vérane ; Bréant, Valentine ; Delpech, Laura

INTRODUCTION:

Exagamglogene autotemcel (Casgevy®) is an ex vivo gene therapy medicinal product (GTMP), derived from the patient's blood stem cells, intended for the treatment of beta-thalassemia. The complexity of this advanced therapy medicinal product (ATMP) required a specific pharmaceutical process at the university hospital of Lyon. This study aims to analyze potential failure modes throughout the Casgevy® process in order to prioritize interventions that need to be implemented.

METHODS AND MATERIALS:

The failure modes and effects analysis (FMEA) method, was conducted as a prospective risk-management approach. The process was mapped to identify potential failure modes and to assess them using three criteria: frequency, likelihood of detection, and severity. The resulting criticality indices (CIs) allowed us to identify the most critical failure modes and to adapt corrective and preventive actions.

RESULTS:

The FMEA led to the identification of 74 failure modes across 11 key process steps. Twenty failure modes were considered as "to treat as a priority". The most critical steps were therapy access and product reconstitution. The working team proposed three types of actions to optimize the pharmaceutical circuit: organizational and collaborative measures, training programs, and, finally, material and logistical enhancements.

DISCUSSION AND CONCLUSION:

This study presents an original FMECA applied to a process designed ex nihilo. While the method has its limitations, particularly concerning the inherent subjectivity of the ratings, a retrospective analysis, conducted after testing the process under real conditions, will be crucial to refine corrective actions.

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项与 Exagamglogene Autotemcel 相关的新闻（医药）

2026-09-05

·今日头条

全球变异/基因改造生物医药开发深度分析！

本文“变异生物医药”是广义概念：mRNA药物、CRISPR‑Cas9基因编辑、碱基编辑、iPSC诱导多能干细胞、CAR‑T细胞治疗、基因修饰细胞、个性化新抗原肿瘤疫苗、基因修饰异种移植；也就是通过人为对核酸、细胞进行基因层面改造而开发的新一代药物；不包含病原体人工改造（生物武器）。全文分发展历程、分国别详细情况、全球成果盘点、技术路线对比、经济‑伦理‑地缘多重影响、风险与未来趋势六大部分展开。一、全球发展完整历程（四大阶段）第一阶段：基础科学期（1961‑1999），理论奠基 1. 1961年mRNA被发现；1990年科学家首次将人工mRNA直接注射动物体内实现蛋白表达，证明mRNA药物的原理可行。 2. 1998年RNA干扰（RNAi）现象被发现，开启基因沉默药物方向；2012年CRISPR‑Cas9被证实可用于人类细胞基因编辑，是整个领域的分水岭。 3. 1998年人类胚胎干细胞建立；2006年山中伸弥发明iPSC诱导多能干细胞，体细胞重编程技术诞生，2012年获得诺贝尔奖。这一时期特点：只有基础科研，没有商业化产品，大量技术瓶颈（递送、免疫反应、脱靶效应）没有解决。第二阶段：早期转化期（2000‑2019），管线起步、多次失败 1. mRNA：Moderna（美国，2010）、BioNTech（德国，2008）成立，主攻肿瘤mRNA疫苗，但是脂质纳米颗粒LNP递送、碱基修饰两大难题迟迟没有完全突破，多数项目止步Ⅰ‑Ⅱ期临床试验。 2. CRISPR基因编辑：大量初创公司诞生（Editas、Beam），早期临床出现安全性事故（早期基因治疗的致命免疫反应），监管机构保持谨慎。 3. CAR‑T：2012年诺华成功实现小女孩Emily的白血病治愈；2017年全球第一款CAR‑T药物获批上市，开启细胞治疗时代。 4. iPSC：日本走在最前面，山中伸弥团队开始帕金森、视网膜病变的早期临床探索。第三阶段：疫情加速爆发期（2020‑2023），mRNA一战成名新冠疫情成为整个变异生物医药产业的催化剂。 1. Moderna、辉瑞‑BioNTech两款mRNA疫苗紧急上市，碱基修饰+LNP递送两大核心技术路线得到大规模人体验证，几年之内数亿人接种，产业从实验室直接进入大规模工业生产阶段。 2. 资本疯狂涌入，全球mRNA、基因编辑、细胞治疗赛道融资额创下历史新高；中国一大批mRNA初创企业快速成立。 3. 各国政府纷纷出台专项产业政策，将基因与细胞药物上升为国家战略赛道。第四阶段：理性回归与分化期（2024‑至今），泡沫出清，真正走向慢病、肿瘤、遗传病治疗 1. mRNA：新冠红利消退，资本泡沫破裂；赛道重心转向个性化肿瘤疫苗、流感、自身免疫病；默沙东mRNA黑色素瘤辅助治疗Ⅲ期取得阳性结果，代表mRNA正式从传染病疫苗转向肿瘤治疗领域。 2. CRISPR基因编辑：2023年Casgevy（exa‑cel）获得FDA批准，用于镰刀型贫血，标志CRISPR基因编辑药物正式商业化，是历史性里程碑。 3. iPSC：日本多条管线进入后期临床、提交上市申请，“现货型干细胞疗法”成为新热点。 4. 全球格局：美国保持龙头；日本在再生医学走出差异化路线；中国管线数量快速增长，但源头核心专利、递送系统短板明显；欧盟监管偏保守；俄罗斯、以色列、韩国走特色路线。二、分国家/地区详细情况：历程、政策、代表性成果、短板（一）美国：全球绝对龙头，全产业链、资本+基础科研双轮驱动发展历程 - 2010‑2019：波士顿‑旧金山两大生物湾，大量基因编辑、mRNA初创诞生，NIH持续大额基础科研投入；FDA设立RMAT再生医学先进疗法快速通道，加速审批创新细胞、基因药物。 - 2020‑2023：Moderna新冠mRNA疫苗大获成功，带动整个行业爆发；CRISPR Therapeutics、Vertex的镰刀型贫血基因编辑疗法快速推进。 - 2024‑现在：重心从传染病转向遗传病、肿瘤、衰老相关疾病、异种器官移植。代表性成果 1. mRNA：Moderna，除新冠外，流感mRNA疫苗、个性化肿瘤新抗原疫苗； 2. CRISPR基因编辑：Casgevy全球首款CRISPR治疗镰刀状细胞贫血；碱基编辑公司Beam Therapeutics多条管线进入临床；刘如谦团队先导编辑（Prime Editing），实现大片段基因精准插入，大幅降低脱靶风险； 3. 异种器官移植：eGenesis基因编辑猪肾脏人体移植，患者不带透析生存超过270天，异种器官移植取得重大进展，有望解决器官捐献短缺难题； 4. CAR‑T、双特异性细胞疗法全球管线数量第一；AI+基因编辑兴起，OpenAI、Retro‑Bio合作多性状基因调控项目，探索衰老干预方向。优势与短板 ✅优势：顶尖高校集群、全球最多的风投资本、FDA灵活加速通道、核心底层专利（CRISPR、LNP脂质纳米颗粒）、完整CDMO生产供应链； ❌短板：价格极其昂贵，已经上市基因药物一剂几十万‑上百万美元，可及性差；伦理争议大（生殖细胞编辑、人体增强）。（二）欧盟（德国、英国、瑞士为主）：基础科研深厚，监管保守，BioNTech为旗帜发展历程欧洲是mRNA的发源地之一：德国BioNTech由土耳其裔科学家夫妇创立，长期深耕肿瘤mRNA；英国是CRISPR早期研究重镇；瑞士拥有龙沙Lonza，全球最重要的细胞与基因药物代工工厂。欧盟EMA监管模式：ATMP先进治疗药物统一审评，安全性标准高，审批周期长，商业化速度落后美国；欧盟地平线计划提供长期科研资助，但风投生态弱于美国。分国家代表 1）德国：BioNTech，新冠一战成名；后新冠时代重回肿瘤mRNA疫苗赛道；美因茨大学为欧洲RNA研究中心； 2）英国：CRISPR基础研究很强；伦敦、剑桥生物技术集群；但产业转化速度慢； 3）瑞士：Lonza是全球最大CGT（细胞与基因治疗）代工企业，美国绝大多数基因编辑药物生产都委托Lonza；诺华CAR‑T全球早期开拓者。特点总结欧洲的模式：科研一流、制造一流、商业化偏弱、监管谨慎；不鼓励生殖细胞编辑，严格区分体细胞治疗和人类基因增强。（三）日本：iPSC再生医学的世界领跑者，一条独特赛道日本不走全面铺开路线，集中资源押注iPSC诱导多能干细胞，走出和美国CRISPR路线差异化的道路。历程 2006山中伸弥发明iPSC；之后日本政府出台《再生医学促进法》，独创条件性限时审批监管路径：严重未满足临床需求的疗法，凭借中期临床数据即可有条件上市，上市之后继续收集真实世界证据；这一套监管制度是日本再生医学弯道超车的关键制度设计。标志性成果 1. 京都大学帕金森病iPSC神经细胞移植：两年随访安全有效，已经提交新药申请，有望成为全球第一款iPSC神经再生药物； 2. 视网膜病变、心衰、软骨修复多条iPSC临床管线；日本已经建立国家级iPSC细胞库，目标开发“现货型”通用细胞产品，不需要患者自体细胞，大幅降低成本； 3. 优势：再生医学临床转化全球第一梯队； 4. 短板：mRNA、CRISPR基因编辑领域相对落后，基础分子生物学创新不足。（四）中国：管线数量高速增长，追赶阶段，优势与瓶颈非常清晰历程 - 2015年前：CGT领域非常薄弱； - 2020‑2022：疫情刺激下一大批mRNA初创企业诞生，资本疯狂涌入； - 2023‑2025：行业洗牌，很多早期mRNA公司出清（斯微生物等），行业回归理性，真正有技术的企业聚焦肿瘤、罕见病方向开展临床； - 当前阶段：临床试验数量约占全球三分之一，仅次于美国，但是底层平台专利、递送系统仍然存在短板。成果 1. CAR‑T：多款国产CAR‑T获批上市，价格相比欧美大幅下降；在淋巴瘤、多发性骨髓瘤实现国产化； 2. mRNA：重心从新冠转向肿瘤个性化疫苗、带状疱疹、流感，多家企业开展Ⅰ‑Ⅱ期临床；LNP递送系统逐步实现国产； 3. CRISPR基因编辑：镰刀型贫血、β‑地中海贫血、眼科遗传病多条CRISPR临床管线； 4. iPSC：神经、心血管领域开展早期临床探索，部分First‑in‑Class全球首创项目； 5. 政策：NMPA建立细胞基因治疗指导原则，逐步完善监管体系，兼顾创新与安全。短板 1. CRISPR、LNP脂质纳米颗粒的底层基础专利大多掌握在美国、欧洲手里； 2. 高端CGT的CDMO供应链还不完善； 3. 源头创新偏少，很多属于fast‑follow快速跟进，真正原创平台技术偏少； 4. 伦理红线：中国法律严格禁止人类生殖细胞基因编辑用于临床（贺建奎事件之后监管极其严格），只允许体细胞基因治疗。（五）韩国、俄罗斯、以色列、印度：特色路线国家韩国三星生物、Celltrion，全球顶级生物药CDMO；细胞治疗、干细胞商业化非常活跃，软骨修复、自体免疫细胞治疗管线众多；监管环境相对宽松，干细胞医疗商业化走得比较靠前。俄罗斯俄罗斯加马利研究所主攻广谱肿瘤mRNA疫苗、艾滋病基因疫苗；不走欧美精细罕见病路线，更倾向广谱、普惠型的免疫疗法；基础科研很强，但生物技术产业生态薄弱，临床试验数量有限，商业化转化能力不足。以色列特拉维夫大学RNA、肿瘤免疫全球知名；初创企业非常活跃；依托强大生命科学基础，个性化肿瘤疫苗领域成果突出。印度定位生物类似药、细胞治疗仿创；主打低成本版本，目标发展中国家市场；原始创新有限，优势在于低成本生产能力。三、全球主要技术路线对比（变异生物医药五大方向）技术路线核心原理代表国家成熟度典型适应症 mRNA药物人工信使RNA进入人体，细胞生产目标蛋白美国、德国中等（肿瘤疫苗快速推进）肿瘤疫苗、传染病疫苗、蛋白缺失病 CRISPR‑Cas9/碱基编辑直接修改人体细胞基因组DNA 美国第一，欧洲、中国跟进早期商业化镰刀型贫血、地中海贫血、遗传性眼病 iPSC干细胞体细胞重编程为多能干细胞，分化为各类人体细胞日本全球领先后期临床‑即将商业化帕金森、心衰、视网膜损伤、关节软骨损伤 CAR‑T细胞治疗改造患者免疫T细胞，靶向杀伤癌细胞美国、中国已经商业化血液肿瘤；实体瘤仍然是世界性难题基因编辑异种移植编辑猪的基因，消除免疫排斥，用猪器官替代人器官美国早期临床肾、心脏移植，解决器官供体紧缺四、全球多维度深远影响（医疗、经济、伦理、地缘政治） 1、临床医学层面：开启精准医疗新时代 1）遗传病的根治方案：过去镰刀型贫血、地中海贫血只有骨髓移植；CRISPR编辑造血干细胞，实现一次性治愈，从长期对症治疗走向根源治愈； 2）难治慢性病：帕金森、心衰、黄斑变性，iPSC细胞替代疗法有望逆转器官损伤； 3）肿瘤治疗范式变革：个性化mRNA肿瘤疫苗，根据每个病人独有的基因突变量身定制，和PD‑1免疫药联合，大幅降低黑色素瘤、胰腺癌术后复发风险； 4）局限：绝大多数技术目前仍然集中于罕见病；实体瘤、衰老干预距离大规模临床落地还很远。 2、经济与产业影响：数万亿美元赛道，国家间新的产业赛道竞争 1）美国已经形成波士顿、旧金山两大CGT产业集群，基因细胞药物成为美国生物医药新的增长引擎； 2）日本押注iPSC，希望通过一条差异化赛道，重塑日本医药产业的全球地位； 3）中国将细胞与基因治疗作为生物医药升级的核心赛道，是从仿制药大国走向创新药强国的关键抓手； 4）产业痛点：基因药物成本极高；如何实现规模化、低成本生产，是全球共同难题。 3、伦理风险：全人类共同的难题 1）体细胞治疗 vs 生殖细胞编辑：体细胞（血液、眼睛）基因修改只针对患者本人，后代不受影响，全球基本认可；生殖细胞（精子卵子胚胎）编辑改变可遗传，会进入人类基因库，全世界绝大多数国家立法禁止； 2）人类增强风险：技术成熟以后，是否允许利用基因编辑提高智商、身高、运动能力，造成“基因富人”与普通人的阶层分化； 3）干细胞来源、动物‑人嵌合、异种器官移植带来一系列伦理争议。 4、地缘政治与科技竞争基因编辑、mRNA递送系统属于战略生物技术，已经成为大国科技博弈新战场： 1）底层核心专利（CRISPR、LNP）成为知识产权竞争的焦点； 2）先进生物医药供应链（CGT的高端CDMO、试剂、载体）存在供应链安全问题； 3）部分国家担忧前沿生物技术两用风险（和平医疗与生物安全边界），各国不断完善生物安全立法。五、当前的瓶颈与未来趋势现存瓶颈 1. 递送问题：如何安全高效把mRNA、基因编辑工具送到人体目标器官（肝脏、大脑、心脏），是行业最大卡脖子难题；肝脏相对容易，脑部、实体瘤仍然非常困难； 2. 安全性：脱靶效应、免疫排斥、长期安全性（基因修改几十年之后是否出现肿瘤风险），长期随访数据仍然稀缺； 3. 成本：一次性基因治疗动辄上百万美元，大规模普惠使用，需要生产工艺革命性突破； 4. 实体瘤难题：CAR‑T、mRNA疫苗对血液肿瘤效果很好；实体肿瘤（肺癌、肝癌、胃癌）仍然是世界性难题。中长期趋势（2026‑2035） 1）分化：美国继续全面领先；日本在iPSC再生医学保持独特优势；中国在细胞治疗、肿瘤mRNA领域加速追赶；欧洲依托强大制造能力，成为全球CGT代工中心； 2）价格下行：现货型通用细胞产品、大规模自动化生产线，逐步把基因药物的价格降下来； 3）监管全球协调：各国在体细胞治疗、生殖细胞编辑的红线问题上逐步形成共识； 4）AI深度赋能：AI用于基因序列设计、脱靶预测、细胞生产工艺优化，AI+基因编辑成为下一代创新的主流范式。

2026-09-02

·全球GCT研究

一次输注一年有效的"血脂疫苗"：CTX310深度解析

ESC 2026 Late-Breaking + NEJM同步发表｜ ANGPTL3降79% ｜无严重AE 事件 CRISPR Tx CTX310 Phase 1a一年随访数据2026.8.28亮相ESC 2026 Late-Breaking并同步发表于NEJM[1][2] 数据 15例;最高剂量(0.8mg/kg):ANGPTL3平均降79%(最高89%)/TG降48%/LDL降53%——效应持续一年[1][2][3] 安全无治疗相关严重不良事件/无≥3级转氨酶升高/无新增安全性事件;1例过敏+3例输注反应(既往已报)[1][4] 意义 "编辑而非沉默"——单次输注持久血脂降低,血脂管理从"终身用药"迈向"一次性编辑"时代[1][3][7][8] 一、引言:血脂管理的"一次性革命" 高血脂是心血管疾病的第一大可控危险因素,但它的管理有个残酷现实:需要终身每日服药——他汀、依折麦布、PCSK9抑制剂,任何一天停药,血脂就会反弹[1][3]。2026年8月28日,CRISPR Therapeutics在ESC 2026 Late-Breaking专场公布CTX310(体内CRISPR-Cas9编辑ANGPTL3)Phase 1a一年随访数据,论文同日发表于NEJM——15例难治性血脂异常患者,最高剂量组ANGPTL3平均降79%、甘油三酯平均降48%、LDL平均降53%,且效应持续一整年,无严重不良事件[1][2][3]。 Cleveland Clinic首席学术官Steven Nissen(研究资深作者)的评价点破核心:"单次治疗具备这种持久性,可能代表我们管理终身血脂疾病方式的重大进步"[1][3]。主要研究者Luke Laffin则指出依从性之痛:"对高危患者,最大挑战往往不是开始治疗,而是坚持治疗"[1][3]。CTX310的12个月数据,是"一次性血脂编辑"从概念走向临床的最强证据[1][2][3]。如果你是一名患者或家属:高血脂治疗正在迎来"打一针管一年甚至更久"的可能——但CTX310仍在临床阶段,他汀/PCSK9抑制剂仍是基石[1][3]。如果你是一名临床医生:ANGPTL3是"三合一"靶点(同时降TG/LDL/HDL调节),CTX310的持久性数据提示未来血脂管理的范式可能从"终身用药"转向"一次性干预"[1][3]。如果你在biotech新药研发:CTX310一年随访是体内基因编辑"持久性"的注册级证据——与nex-z(TTR)、VERVE-102(PCSK9)、STX-1150(表观遗传)共同定义血脂编辑赛道格局[1][7][8][9]。二、事件核心:ESC 2026 Late-Breaking + NEJM同步发表表1|CTX310 Phase 1a一年随访关键数据(2026.8.28 ESC 2026+NEJM) 项目详情公司 CRISPR Therapeutics(Nasdaq: CRSP)——CASGEVY(全球首个CRISPR疗法)开发商[1][4] 技术体内CRISPR-Cas9基因编辑,LNP递送至肝脏,切割ANGPTL3基因[1] 适应症 HoFH/HeFH/重度高甘油三酯血症(sHTG)/混合型血脂异常[1] 试验 Phase 1a:开放标签剂量递增,15例,5个剂量组(0.1-0.8 mg/kg lean体重),全部完成≥1年随访[1] 最高剂量疗效(0.8 mg/kg) ANGPTL3平均降79%(最高89%)/TG平均降48%(最高78%)/LDL平均降53%(最高84%)——一年随访持续[1][2][3] 安全性无治疗相关严重不良事件;无≥3级转氨酶升高;无剂量限制性毒性;无新增治疗相关不良事件[1] 既往事件 1例过敏反应(次日缓解);3例输注相关反应(2级,均完成输注);1例短暂转氨酶升高(均此前已报道)[1][4] 背景治疗多数接受他汀/依折麦布;40%接受PCSK9抑制剂[1] 发表 ESC 2026 Late-Breaking(2026.8.28)+NEJM同步发表(Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310,DOI:10.1056/NEJMc2609825)[1][2] 下一步 Phase 1b(固定剂量0.8 mg/kg等效,重度高甘油三酯血症队列);2026 H2更新[1] 官方口径解读:(1)发表形式——ESC 2026(慕尼黑,8.28-31)Late-Breaking专场口头报告+NEJM同步发表(Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310,DOI:10.1056/NEJMc2609825)——顶刊+顶级会议双重背书[1][2];(2)CMO Naimish Patel——"单次给药产生持久血脂降低,是我们开发心代谢疾病一次性治疗目标的核心"[1];(3)Steven Nissen(Cleveland Clinic)——"单次输注的降低持续到一年,提示持续的生物效应"[1][3];(4)Luke Laffin(主要研究者)——"单次输注一年持久,是帮助弥合依从性缺口的令人鼓舞的信号"[1][3];(5)关键表述——"深入且持久的ANGPTL3编辑"——编辑(edit)而非沉默(silence):基因被永久改变[1][5];(6)行业传播——GlobeNewswire官方通稿+HCPLive等权威媒体同步报道ESC 2026数据[5][6]。三、技术深度:体内CRISPR-Cas9编辑ANGPTL3 CTX310的技术设计:(1)递送——专有LNP(脂质纳米颗粒)平台将CRISPR-Cas9 mRNA+向导RNA递送至肝脏——肝脏是ANGPTL3的主要产生部位[1];(2)编辑——Cas9在ANGPTL3基因特定位点切割DNA,引入插入/缺失(indel)使基因失活——永久性编辑,蛋白不再产生[1];(3)给药——单次静脉输注(Phase 1a剂量0.1-0.8 mg/kg lean体重)[1];(4)平台延伸——CRISPR Tx的体内肝脏编辑组合拳:CTX310(ANGPTL3)+CTX340(AGT,高血压)+CTX321(LPA,Lp(a))+CTX460(SERPINA1,SyNTase编辑)——同一LNP平台多靶点复用[10];(5)SyNTase™——公司新型专有编辑技术(更精准/高效/可扩展的基因校正),下一代管线载体[10];(6)vs核酸药物——siRNA/ASO(需反复注射)vs CRISPR(一次性)——编辑的"永久性"是根本差异[1][7][9]。四、ANGPTL3生物学:为什么是"三合一"靶点 ANGPTL3(血管生成素样蛋白3)的独特地位:(1)机制——ANGPTL3抑制脂蛋白脂肪酶(LPL)与内皮脂肪酶(EL),从而升高甘油三酯;同时影响LDL代谢——"一个靶点,三重血脂改善"[1];(2)遗传学验证——ANGPTL3功能缺失突变携带者:TG和LDL均降低,且冠心病风险显著下降——人类遗传学为靶点提供天然因果证据[1];(3)罕见病极端验证——家族性低β脂蛋白血症样表型(ANGPTL3双等位基因缺失)个体血脂极低且健康——"天然基因敲除"的安全窗[1];(4)现有干预——evinacumab(ANGPTL3单抗)已获批用于HoFH,但需终身给药——CTX310以一次性编辑替代[1][3];(5)适应症谱——HoFH(罕见/严重)/HeFH/重度高甘油三酯血症/混合型血脂异常——从罕见病到常见病全覆盖[1]。五、临床数据:Phase 1a一年随访 Phase 1a一年数据的六层解读:(1)剂量依赖——ANGPTL3降低呈剂量依赖,0.8 mg/kg组最强[1];(2)深度——最高剂量组:ANGPTL3平均降79%(最高89%)——接近"功能性敲除"水平[1][2];(3)持久性——一年随访效应持续——这是本次数据新增的核心价值(此前2025.11仅2个月数据)[1][4];(4)血脂转化——TG平均降48%(最高78%)、LDL平均降53%(最高84%)——ANGPTL3下降有效转化为血脂改善[1][2][3];(5)人群——15例难治性血脂异常(背景他汀/依折麦布,40%用PCSK9抑制剂)仍显著获益——"难治"人群的增量价值[1];(6)局限——开放标签、样本量小(15例)、无安慰剂对照——Ph1b(重度高甘油三酯血症队列)与后续确证试验将提供更强证据[1]。六、安全性:无严重不良事件、无≥3级肝酶 CTX310的安全性画像:(1)核心结论——无治疗相关严重不良事件、无≥3级转氨酶升高、无剂量限制性毒性、无新增治疗相关不良事件(一年随访)[1];(2)既往事件(均先前已报道,非新增)——1例过敏反应(次日缓解);3例输注相关反应(2级,均完成输注);1例短暂转氨酶升高(治疗后早期,此后无肝酶升高)[1][4];(3)对比nex-z的肝毒性事件——Intellia nex-z曾现Grade 4肝毒性触发临床暂停——CTX310的无≥3级肝酶数据,对"LNP肝脏编辑安全性"是重要正面信号[1][9];(4)长期风险——编辑的永久性意味着脱靶效应不可逆——需长期随访监测(肝细胞克隆扩增/脱靶编辑的潜在致癌风险)[1][9];(5)免疫原性——LNP/Cas9蛋白的免疫应答(抗Cas9抗体/抗LNP抗体)影响重复给药——CTX310设计为单次给药,降低免疫原性影响[1]。七、从2个月到12个月:持久性的"证据跃迁" 本次数据与既往数据的对比意义:(1)2025年:2个月数据(NEJM 2025,Laffin等)——首次人体验证:快速(2周内)且深度的ANGPTL3/LDL/TG降低——但"短期效应"可能被质疑为LNP非特异性或暂时效应[4];(2)2026年:12个月数据——效应持续一年,证明是"编辑"带来的持久生物学改变,而非瞬时效应——这是从"初步信号"到"持久证据"的跃迁[1][2];(3)对监管的意义——一年持久性数据支撑Ph1b/确证试验设计与BLA路径;替代终点(ANGPTL3/TG/LDL)到临床结局(心血管事件)的桥接仍需大规模试验[1];(4)对行业的意义——体内基因编辑的"持久性证明"首次在血脂领域达成——nex-z(TTR三年)、CTX310(血脂一年)共同建立"一次性体内编辑"的临床可信度[1][9]。八、竞争格局:体内编辑血脂赛道表2|体内编辑血脂赛道竞争格局(2026) 管线/公司技术靶点阶段关键数据 CTX310(CRISPR Tx)[1][2][3] CRISPR-Cas9(LNP) ANGPTL3 Ph1a完成/Ph1b进行一年随访:ANGPTL3降79%/TG降48%/LDL降53%[1][2] nex-z(NTLA-2001,Intellia)[9] CRISPR-Cas9(LNP) TTR Ph3 MAGNITUDE 三年TTR降≥90%;曾因肝毒性暂停后解除[9] VERVE-102(Verve)[8] 碱基编辑(ABE) PCSK9 Ph1 LDL-C降62%(单次输注,报道);ACC 2026科学声明重点[8] STX-1150(Scribe)[7] 表观遗传沉默 PCSK9 临床前/IND推进 PCSK9降90%/LDL-C降68%;单剂量数年[7] CTX340(CRISPR Tx)[10] CRISPR-Cas9(LNP) AGT Ph1(NCT07758634) 难治性高血压;AGT持续降低(已核实基线)[10] CTX321(CRISPR Tx)[10] CRISPR-Cas9(LNP) LPA 开发中 Lp(a)升高患者[10] 血脂体内编辑赛道的多维竞争:(1)CTX310(CRISPR切割ANGPTL3)——"三合一靶点"+一年持久性——先发优势明确[1];(2)VERVE-102(碱基编辑PCSK9)——PCSK9是LDL主战场(患者池更大),碱基编辑不产生双链断裂——LDL-C降62%报道——"单靶点LDL"vs CTX310"三合一"的路线之争[8];(3)STX-1150(表观遗传PCSK9)——不切割DNA、理论可逆——"后切割时代"代表[7];(4)nex-z(TTR,CRISPR)——虽非血脂,但同为LNP肝脏编辑——验证平台安全性/持久性的参照系[9];(5)判断——CTX310证明"ANGPTL3三合一+一年持久"的临床价值;PCSK9阵营(PCSK9抑制剂已证明疗效)需证明"编辑优于单抗";表观遗传阵营需证明"可逆性是真优势"[1][7][8]。九、临床意义:依从性革命与"血脂疫苗" CTX310的临床与公共卫生意义:(1)依从性之痛——Laffin:"最大挑战不是开始治疗而是坚持治疗"——每日服药/定期注射的终身依从性,是心血管一级/二级预防的全球性难题[1][3];(2)"血脂疫苗"概念——单次输注提供多年(理论上终身)血脂控制——类似"疫苗式"的预防逻辑,可能重塑一级预防(高危人群早期干预)[1][3];(3)难治人群——HoFH(对常规治疗抵抗)/重度高甘油三酯血症(胰腺炎风险)——CTX310对"无药可用/用药无效"人群价值最大[1];(4)与单抗的竞争——evinacumab(ANGPTL3单抗)需终身给药,CTX310一次完成——治疗负担与长期成本优势[1][3];(5)风险分层——未来或用于"基因风险最高"人群(家族性高胆固醇血症/早发心血管病家族史)——精准预防[1]。十、管线延伸:CTX340/CTX321/CTX460与心血管编辑组合拳 CRISPR Tx的体内心血管编辑组合拳:(1)CTX340(AGT,难治性高血压)——靶向血管紧张素原,Ph1(NCT07758634),此前AHA 2025 Ph1+ESC 2026持久疗效(已核实基线)——与CTX310共享LNP平台[10];(2)CTX321(LPA,Lp(a))——靶向脂蛋白(a)——Lp(a)由遗传决定、无药可医(现有PCSK9抑制剂对Lp(a)降幅有限)——编辑LPA是"空白市场"卡位[10];(3)CTX460(SERPINA1,SyNTase编辑)——α1抗胰蛋白酶缺乏症——SyNTase(新型编辑技术)首秀[10];(4)平台逻辑——同一LNP肝脏递送平台,多靶点复用——"平台价值"随管线扩展而放大[1][10];(5)对CRISPR Tx的意义——CASGEVY(体外编辑,血液病)已商业化;体内编辑(心血管)是第二增长曲线——CTX310是旗舰[1][4][10]。十一、挑战与风险 CTX310面临的挑战:(1)证据强度——15例开放标签、无对照、替代终点(血脂)而非硬终点(心血管事件)——注册需大规模随机对照确证[1];(2)长期安全性——编辑的永久性:脱靶编辑、肝细胞克隆扩增、理论致癌风险——需超长期随访(数年-终身)[1][9];(3)肝毒性——LNP肝脏编辑的肝酶升高风险(nex-z前车之鉴)——CTX310暂未现≥3级,但样本小[1][9];(4)免疫原性——抗Cas9抗体可能影响疗效或安全——单次给药设计部分缓解[1];(5)竞争——PCSK9阵营(VERVE-102碱基编辑,患者池更大)+表观遗传(STX-1150)+TTR平台(Intellia)——赛道拥挤,差异化窗口有限[7][8][9];(6)支付——"一次治疗"定价对标CASGEVY量级($百万级)vs终身他汀/PCSK9抑制剂的成本——大适应症(高血脂)的支付博弈将更激烈[1][8]。十二、给各方建议(三类读者全覆盖) 12.1 给患者与家庭 (1)CTX310仍处Ph1b,他汀/依折麦布/PCSK9抑制剂仍是血脂管理基石——勿因"基因疗法"叙事中断现有治疗[1];(2)家族性高胆固醇血症/重度高甘油三酯血症患者可关注CTX310临床试验入组(尤其对现有治疗抵抗者)[1];(3)理性看待"打一针管一年"——长期安全数据(数年随访)尚未成熟[1][9]。 12.2 给临床医生 (1)理解ANGPTL3靶点的"三合一"机制(抑制LPL/EL→降TG,降LDL)——evinacumab已临床验证靶点可及性[1][3];(2)关注CTX310 Ph1b(重度高甘油三酯血症)数据与长期安全性随访——转介适合患者入组[1];(3)对患者教育:基因编辑的持久性既是优势(依从性)也是责任(不可逆),知情同意需充分[1][9]。 12.3 给biotech/投资者 (1)技术评估——CTX310一年持久性(ANGPTL3降79%)是体内编辑"持久性"的注册级证据;与nex-z(TTR三年)共同确立LNP肝脏编辑可行性[1][9];(2)竞争定位——ANGPTL3"三合一"vs PCSK9"单靶点大市场"(VERVE-102/STX-1150)——适应症广度vs患者池大小的权衡[7][8];(3)风险定价——15例开放标签数据的估值需含"Ph1b/确证试验失败+长期安全性事件"折价[1];(4)中国机会——国产LNP+编辑工具的血脂管线可差异化(成本优势);注意FTO(CRISPR专利格局)与长期随访要求[1][8][10]。十三、结语:编辑时代的心血管预防 CTX310的一年随访数据,把体内基因编辑从"科学演示"推向"临床证据":单次输注,ANGPTL3深度编辑,血脂全面改善,持续整整一年,且安全性干净[1][2][3]。Steven Nissen称之为"管理终身血脂疾病的潜在重大进步"[1][3]。当CASGEVY证明"体外编辑可治愈血液病",当CTX310证明"体内编辑可持久管理慢性病",当nex-z、VERVE-102、STX-1150在不同靶点竞速——心血管疾病正从"终身用药时代"迈入"一次性编辑时代"[1][7][8][9][10]。但15例的样本与替代终点的局限提醒:编辑的永久性力量,必须配以同等分量的长期证据责任[1]。血脂管理的下一个十年,将由"依从性"与"持久性"的赛跑定义——而CTX310,已经为"持久性"写下浓墨重彩的一章[1][3]。希望加入“全球GCT行业交流群”的读者，请加以下二维码联系工作人员参考文献 [1]CRISPR Therapeutics官方IR(2026.8.28):Presents Phase 1a Data for CTX310——ESC 2026 Late-Breaking;15例一年随访;最高剂量ANGPTL3降79%(最高89%)/TG降48%(最高78%)/LDL降53%(最高84%);无严重AE无≥3级转氨酶;Ph1b推进 · CRISPR Therapeutics(官方IR) [2]NEJM(2026):Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310——ESC 2026同步发表(DOI:10.1056/NEJMc2609825) · NEJM(2026) · DOI:10.1056/NEJMc2609825 [3]Cleveland Clinic新闻稿(2026.8.28):First-In-Human Trial of CRISPR Gene Editing Therapy Safely and Continuously Lowers Cholesterol and Triglycerides After One Year——Nissen/Laffin评论 · Cleveland Clinic(官方) [4]Laffin et al. NEJM 2025(PMID 41211945):CTX310 Phase 1a初步数据——2个月数据,1例过敏反应/3例输注反应/1例短暂转氨酶升高(既往已报道) · NEJM(2025) · PMID:41211945 [5]GlobeNewswire(2026.8.28):CRISPR Therapeutics Presents Phase 1a Data for CTX310——官方通稿 · GlobeNewswire(官方通稿) [6]HCPLive(2026):CTX310 Gene Editing Sustains ANGPTL3, LDL Reductions at 1 Year——ESC 2026报道 · HCPLive(行业媒体) [7]BioSpace(2026):Scribe Therapeutics STX-1150——临床阶段表观遗传沉默PCSK9(PCSK9降90%/LDL-C降68%,单剂量数年) · BioSpace(行业媒体) [8]ACC 2026 Scientific Statement(行业报道):Gene Editing Therapy in Cardiovascular Disease——VERVE-102碱基编辑PCSK9为领先案例(LDL-C降62%报道) · ACC科学声明(转引行业报道) [9]Intellia官方IR(2026):nex-z(NTLA-2001)Positive Longer-Term Phase 1 Data——三年TTR降≥90%;III期MAGNITUDE(Grade 4肝毒性后解除暂停)——LNP肝脏编辑安全参照 · Intellia(官方IR) [10]CRISPR Therapeutics官方:In Vivo Liver Editing Programs——CTX310(ANGPTL3)/CTX340(AGT,Ph1 NCT07758634)/CTX321(LPA)/CTX460(SERPINA1,SyNTase) · CRISPR Therapeutics(官方)

临床结果基因疗法疫苗临床研究

2026-09-02

·GlobeNewswire-Health Care

CRISPR Therapeutics Presents Phase 1a Data for CTX310® Demonstrating Deep and Durable ANGPTL3 Editing, Triglyceride and LDL Lowering at ESC Congress 2026

-Data presented in a late-breaking presentation at the European Society of Cardiology (ESC) Congress 2026- -Phase 1a clinical data for CTX310® continued to demonstrate robust, dose-dependent reductions in circulating ANGPTL3 with a mean reduction from baseline of 79% (maximum 89%), a mean reduction in triglycerides (TG) of 48% (maximum 78%), and a mean reduction of low-density lipoprotein (LDL) of 53% (maximum 84%) at the highest dose- -CTX310 was well tolerated with no treatment-related serious adverse events, no ≥Grade 3 changes in liver transaminases, and no additional treatment-related adverse events since the previous update- -Findings simultaneously published in The New England Journal of Medicine entitled “Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310”- Aug. 28, 2026 -- CRISPR Therapeutics (Nasdaq: CRSP) today presented durability data from its Phase 1a clinical trial evaluating CTX310®, an investigational, in vivo CRISPR/Cas9 gene editing therapy targeting ANGPTL3. A single-course treatment with CTX310 produced deep and durable reductions in circulating ANGPTL3, triglycerides (TG), and low-density lipoprotein (LDL) that were sustained through one year of follow-up. At the highest dose, mean reductions from baseline were 79% (maximum 89%) for ANGPTL3, 48% (maximum 78%) for TG, and 53% (maximum 84%) for LDL. These extended follow-up data demonstrate the durability of CTX310's effect and support its potential to deliver long-lasting lipid lowering after a single intravenous (IV) infusion. These data were presented today during a late breaking session at the European Society of Cardiology (ESC) Congress 2026 and extend the Phase 1 results previously presented. The data were also published today in The New England Journal of Medicine (NEJM) in a peer reviewed article entitled "Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310." CRISPR Therapeutics is advancing CTX310 in a Phase 1b clinical trial, with U.S. and ex-U.S. trials ongoing, and expects to provide an additional update on the CTX310 program in the second half of 2026. "These durability data mark an important next step for the CTX310 program and for the field of in vivo gene editing," said Naimish Patel, M.D., Chief Medical Officer, CRISPR Therapeutics. "Evidence that a single dose can produce lasting lipid lowering is central to our goal of developing one-time treatments for cardiometabolic diseases. These results provide strong support for continued advancement of CTX310 and our broader cardiovascular gene editing portfolio, and we look forward to sharing new data from the severe hypertriglyceridemia cohort of the CTX310 Phase 1b trial in the second half of this year." "For patients at high cardiovascular risk, the biggest challenge is often not starting therapy but staying on it, since daily medications require lifelong adherence that many patients are unable to maintain," said Luke Laffin, M.D., principal investigator and Medical Director of the Cleveland Clinic Coordinating Center for Clinical Research. "A single infusion producing durable reductions at one-year is an encouraging signal that a one-time approach could help close that adherence gap." "What is compelling about this update is that the reductions in ANGPTL3, triglycerides, and LDL from a single infusion have persisted out to one-year, suggesting a sustained biological effect," said Steven E. Nissen, M.D., senior author of the study and Chief Academic Officer at the Cleveland Clinic Heart, Vascular and Thoracic Institute. "A one-time treatment with this degree of durability could represent a meaningful advance in how we manage lifelong lipid disorders." The Phase 1a portion of the study was an open label, dose-escalation trial evaluating single-course IV doses of CTX310 ranging from 0.1 to 0.8 mg/kg (lean body weight) targeting ANGPTL3 in four patient groups: homozygous familial hypercholesterolemia (HoFH), severe hypertriglyceridemia (sHTG), heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemias (elevated TG and LDL). Eligible participants had uncontrolled TG levels >150 mg/dL and/or LDL cholesterol >100 mg/dL (or >70 mg/dL for those with established ASCVD) despite background standard of care per local guidelines. The majority of participants were receiving statins and/or ezetimibe, while 40% were taking PCSK9 inhibitors. The trial was designed to evaluate safety and tolerability as primary endpoints, with changes in circulating ANGPTL3 protein, TG, and LDL as secondary endpoints. Single-course ascending doses of CTX310 were administered to 15 participants across sequential cohorts, and all participants completed at least one-year of follow-up as of the data cutoff. CTX310 was generally well tolerated, and no dose-limiting toxicities or serious adverse events related to treatment. Adverse events were generally mild to moderate. As previously reported in Laffin et al. (2025), one participant experienced an allergic reaction that resolved the following day with supportive care. Infusion-related reactions occurred in three participants (two at 0.6 mg/kg and one at 0.8 mg/kg dose), all Grade 2. All events resolved, and all participants completed their infusions. Beyond the transient aminotransferases elevation previously reported in one participant shortly after treatment, there were no liver function test elevations throughout the remainder of the trial. The safety events described above were previously reported in Laffin et al. (New England Journal of Medicine, 2025) and reflect the initial treatment period of the Phase 1a clinical trial. No new treatment-related safety events were observed during extended follow-up. These new results build upon previously disclosed clinical data from 15 participants across four sequential cohorts, corresponding to lean body weight-based doses of DL1 [0.1 mg/kg], DL2 [0.3 mg/kg], DL3 [0.6 mg/kg], DL3.5 [0.7 mg/kg] and DL4 [0.8 mg/kg]. All participants had at least one-year of follow-up. Dose dependent reductions in circulating ANGPTL3 protein were sustained through one-year following CTX310 infusion. Among participants treated at 0.8 mg/kg, ANGPTL3 reductions of up to 89% were observed, with a mean reduction of 79% at one-year following CTX310 infusion. The Phase 1b portion of the trial examines a fixed flat dose regimen of CTX310 equivalent to the most efficacious dose in Phase 1a (0.8mg/kg). CRISPR Therapeutics continues to anticipate sharing an update from the CTX310 Phase 1b clinical trial in the second half of 2026, focused on severe hypertriglyceridemia patients. CRISPR Therapeutics has established a proprietary lipid nanoparticle (LNP) delivery platform to enable gene editing in the liver using both CRISPR/Cas9 and its novel, proprietary SyNTase™ editing technology. The Company's in vivo portfolio includes three cardiovascular programs: CTX310, targeting angiopoietin-related protein 3 (ANGPTL3), in development for heterozygous and homozygous familial hypercholesterolemia, mixed dyslipidemias, and severe hypertriglyceridemia; CTX340™, targeting angiotensinogen (AGT), in development for refractory hypertension; and CTX321™, targeting LPA, in development for patients with elevated lipoprotein(a) [Lp(a)]. In addition, the Company's disclosed development candidates also include CTX460™, targeting SERPINA1 using SyNTase editing, for the treatment of alpha-1 antitrypsin deficiency (AATD). CRISPR Therapeutics is a leading biopharmaceutical company focused on developing transformative gene-based medicines for serious human diseases. Founded over a decade ago as an early pioneer in CRISPR/Cas9 gene editing, the Company has evolved from a pioneering research-stage organization into an industry leader, marking a historic milestone with the approval of CASGEVY® (exagamglogene autotemcel [exa-cel]), the world’s first CRISPR-based therapy, for eligible patients with sickle cell disease and transfusion-dependent beta thalassemia. Today, CRISPR Therapeutics is advancing a broad, diversified pipeline spanning hemoglobinopathies, cardiovascular disease, autoimmune disease, oncology, regenerative medicine and rare diseases. The Company is also expanding its gene editing toolkit through SyNTase™ editing, its novel, proprietary platform designed to enable precise, efficient, and scalable gene correction. To accelerate its impact, CRISPR Therapeutics has established strategic collaborations with leading biopharmaceutical partners, including Vertex Pharmaceuticals. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California. 、、 CRISPR THERAPEUTICS® standard character mark and design logo, CTX310®, CTX321™, CTX340™, CTX460™ and SyNTase™ are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners. Reference Laffin L, et al. Phase 1 Trial of CRISPR-Cas9 Gene Editing Targeting ANGPTL3. The New England Journal of Medicine. 2025. 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临床结果基因疗法

100 项与 Exagamglogene Autotemcel 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D12749	-	-	DB15572

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
β地中海贫血	美国	Vertex Pharmaceuticals, Inc.	2024-01-31
镰状细胞血症	英国	Vertex Pharmaceuticals (Europe) Ltd. (Ireland)	2023-11-15
输血依赖性β地中海贫血	英国	Vertex Pharmaceuticals (Europe) Ltd. (Ireland)	2023-11-15

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
输血依赖性地中海贫血	临床3期	美国	CRISPR Therapeutics AG	2022-05-03
输血依赖性地中海贫血	临床3期	美国	Vertex Pharmaceuticals, Inc.	2022-05-03
输血依赖性地中海贫血	临床3期	加拿大	CRISPR Therapeutics AG	2022-05-03
输血依赖性地中海贫血	临床3期	加拿大	Vertex Pharmaceuticals, Inc.	2022-05-03
输血依赖性地中海贫血	临床3期	德国	Vertex Pharmaceuticals, Inc.	2022-05-03
输血依赖性地中海贫血	临床3期	德国	CRISPR Therapeutics AG	2022-05-03
输血依赖性地中海贫血	临床3期	意大利	CRISPR Therapeutics AG	2022-05-03
输血依赖性地中海贫血	临床3期	意大利	Vertex Pharmaceuticals, Inc.	2022-05-03
输血依赖性地中海贫血	临床3期	英国	Vertex Pharmaceuticals, Inc.	2022-05-03
输血依赖性地中海贫血	临床3期	英国	CRISPR Therapeutics AG	2022-05-03

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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


NCT05356195 \| NCT05329649 (CLIMB THAL-141, Pubmed \| N Engl J Med)	临床3期	输血依赖性地中海贫血 \| 镰状细胞血症	26	Exagamglogene autotemcel (transfusion-dependent β-thalassemia)	糧遞鹽網蓋淵憲糧憲鑰(鬱願衊鏇製構遞淵鑰製) = 製淵積夢顧觸壓鏇窪膚鹽願構願簾憲鬱鹽膚夢 (醖齋鏇製餘糧糧獵艱糧 )	积极	2026-06-10
				Exa-cel (sickle cell disease)	獵顧選壓淵衊鑰鹽壓願(觸構繭鑰膚衊憲齋衊夢) = 願鏇憲廠繭淵範餘鹹顧蓋廠醖獵衊壓願遞齋鹹 (艱製範鬱衊淵窪衊夢選 )
NCT03655678 (CLIMB THAL-141, EHA2026)	临床3期	血管闭塞危机 \| 输血依赖性β地中海贫血	24	Exagamglogene autotemcel (transfusion-dependent β‐thalassemia)	鬱遞醖餘鹹鏇築廠範鏇(窪襯窪鑰膚顧鹹鏇範簾) = 顧窪鬱鏇衊顧鬱範鑰夢願獵網鹹簾糧鏇選醖願 (積廠鹽窪艱廠夢繭選鑰 ) 更多	积极	2026-05-12
				Exagamglogene autotemcel (sickle cell disease with recurrent vaso-occlusive crises)	鬱遞醖餘鹹鏇築廠範鏇(窪襯窪鑰膚顧鹹鏇範簾) = 顧淵繭衊壓繭艱鑰憲糧願獵網鹹簾糧鏇選醖願 (積廠鹽窪艱廠夢繭選鑰 ) 更多
NCT03745287 (CLIMB-131, EHA2026)	临床3期	镰状细胞血症	45	Exagamglogene autotemcel	鏇遞膚夢獵廠窪憲醖膚(繭憲衊簾餘範襯憲簾醖) = There was one death which occurred 0.7 years after exa-cel infusion, which was previously reported, from respiratory failure due to COVID-19 infection not related to exa-cel 夢窪憲壓鏇觸構鑰窪築 (築廠衊醖簾積鏇衊膚鹹 ) 更多	积极	2026-05-12
NCT03655678 (CLIMB THAL-111, EHA2026)	临床3期	输血依赖性地中海贫血	56	Exagamglogene autotemcel (Transfusion-dependent β-thalassemia)	淵鹹範鏇窪築選衊築範(鹹夢廠窪顧積鹽淵蓋簾) = 鏇鹽獵壓衊鏇鬱齋餘選憲簾鏇蓋範鏇衊艱醖願 (糧簾繭簾網淵夢獵製蓋 )	积极	2026-05-12
NCT03745287 (CLIMB-111, EBMT2026)	临床3期	输血依赖性地中海贫血 \| 镰状细胞血症	102	Exagamglogene autotemcel	簾鹽餘夢蓋獵鑰蓋淵遞(鹽蓋繭遞觸鬱壓膚網憲) = 積衊淵製簾繭範製膚顧網窪膚簾範衊鑰範襯顧 (網艱鏇繭襯糧壓鹹觸網 ) 更多	积极	2026-03-22
				Exagamglogene autotemcel (SCD)	襯製蓋醖壓鹹簾壓窪鹹(醖鬱顧壓簾淵艱構獵蓋) = 衊鏇築鹹製淵壓範餘獵積蓋觸構齋齋襯衊醖夢 (選壓願衊鹹壓顧積鏇觸 ) 更多
NCT03655678 (CLIMB THAL-111, Tandem Meetings ASTCT and CIBMTR2026)	临床3期	输血依赖性地中海贫血 \| 镰状细胞血症 CRISPR-Cas9 gene edited	102	Exagamglogene autotemcel + Exagamglogene autotemcel (Transfusion-dependent β-thalassemia)	簾憲淵築廠醖製鑰蓋廠(顧顧餘憲淵衊獵窪繭膚) = 鹽蓋簾鹽衊網願構築淵艱鹹鑰膚鑰繭範構艱獵 (艱壓鑰繭製網製網遞壓 ) 更多	积极	2026-02-04
				Exagamglogene autotemcel + Exagamglogene autotemcel (Sickle Cell Disease)	簾憲淵築廠醖製鑰蓋廠(顧顧餘憲淵衊獵窪繭膚) = 憲顧糧糧憲襯衊壓醖觸艱鹹鑰膚鑰繭範構艱獵 (艱壓鑰繭製網製網遞壓 ) 更多
NCT03655678 (CLIMB-111, Tandem Meetings ASTCT and CIBMTR2026)	临床3期	输血依赖性地中海贫血 \| 镰状细胞血症	102	Exagamglogene autotemcel (Transfusion-dependent β-thalassemia)	鏇簾醖鬱獵願選積廠衊(壓膚憲製顧蓋簾襯艱艱) = There were no malignancies through follow-up in CLIMB-131. 窪襯餘醖鑰觸積繭蓋艱 (選積艱範壓網壓鹹顧窪 )	积极	2026-02-04
				Exagamglogene autotemcel (Sickle Cell Disease)
NCT05356195 \| NCT05329649 (CLIMB SCD-151, ASH2025 \| Company_Website) 人工标引	临床3期	输血依赖性地中海贫血 \| 镰状细胞血症	23	Exagamglogene autotemcel (transfusion-dependent β-thalassemia (CLIMB THAL-141))	齋築繭壓繭艱範鏇廠餘(獵淵壓築衊夢壓願鏇觸) = 鹹積憲廠醖鏇齋願餘願醖鏇觸選顧繭襯憲衊襯 (願鹽醖鹽築餘顧醖襯鏇 ) 更多	积极	2025-12-06
				Exagamglogene autotemcel (sickle cell disease (CLIMB SCD-151))	蓋鬱鏇獵醖艱獵願衊艱(獵窪襯艱積構鹽顧獵願) = 齋鬱築繭鑰築襯壓遞糧膚製蓋鏇簾製積膚壓齋 (餘衊餘鹽憲餘觸淵範淵 ) 更多
NCT03745287 \| NCT04208529 (CLIMB-131, ASH2025 \| Pubmed) 人工标引	临床3期	镰状细胞血症	45	Exagamglogene autotemcel (CLIMB SCD‑121)	鹹壓醖鏇網夢網觸糧製(網顧糧壓願餘壓夢鹹鹽) = 範顧醖網築壓齋壓夢鬱餘選網網襯壓遞襯鹹繭 (顧壓獵壓製蓋網鬱膚艱, 78.8 ~ 97.5) 更多	积极	2025-12-06
				Exagamglogene autotemcel (CLIMB SCD‑121 + CLIMB-131 combined (LTFU))	鹹壓醖鏇網夢網觸糧製(網顧糧壓願餘壓夢鹹鹽) = 鹹鏇蓋構淵鑰鑰齋構窪餘選網網襯壓遞襯鹹繭 (顧壓獵壓製蓋網鬱膚艱 ) 更多
NCT03655678 (CLIMB-111, ASH2025)	临床3期	输血依赖性地中海贫血	56	Exagamglogene autotemcel	顧願淵衊築廠顧膚範顧(憲窪餘構顧糧鹽鑰製鹹) = 餘遞築獵襯簾願觸夢鑰鹽鏇壓蓋壓繭憲窪夢壓 (網艱鏇選鏇蓋網壓壓鏇 ) 更多	积极	2025-12-06