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2024-04-01

申办/合作机构

Vertex Pharmaceuticals, Inc.

ChiCTR2300073795

/ Recruiting早期临床1期IIT

An International, Multicenter, Phase I Open Label Study to Evaluate Safety and Efficacy of Administration of Autologous CD34+ Cells Gene Edited Ex Vivo Using a CRISPR/AAV6 Platform to Introduce a Codon Optimized cDNA Version of the Red-Cell Type Pyruvate Kinase Genein Adult and Pediatric Patients with Severe Pyruvate Kinase

开始日期2023-11-09

申办/合作机构

上海交通大学医学院附属上海儿童医学中心

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.

100 项与 Exagamglogene Autotemcel 相关的临床结果

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100 项与 Exagamglogene Autotemcel 相关的转化医学

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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）

2025-05-01·PHARMACOECONOMICS

Innovative Payment Models for Sickle-Cell Disease Gene Therapies in Medicaid: Leveraging Real-World Data and Insights from CMMI’s Gene Therapy Access Model

Article

作者: Nair, Kavita ; Leonard, Jim ; DiStefano, Michael J ; Wright, Garth C ; Zemplenyi, Antal ; Anderson, Kelly E ; McQueen, R Brett

OBJECTIVE:

This study aims to evaluate the financial implications of implementing various payment models, including outcome-based agreements (OBAs), volume-based rebates, and guaranteed rebates, for the newly approved gene therapies, exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel), in the treatment of sickle-cell disease (SCD) from the perspective of Colorado Medicaid. The analysis specifically examines the cost of standard of care (SoC) for severe SCD, the impact of different eligibility criteria based on vaso-occlusive events (VOEs), and the potential financial impacts associated with rebate structures.

METHODS:

Data from the Colorado Department of Health Care Policy & Financing (HCPF) database was used to estimate the annual costs for Medicaid-enrolled patients with severe SCD from 2018 to 2023. Patients were selected based on various eligibility criteria, including the number of VOEs, acute chest syndrome events, and stroke diagnoses. Three-state Markov models (SCD, stable, and dead) were constructed to compare the costs of SoC and gene therapies. The durability of gene therapy effectiveness and the financial impact of OBAs, volume-based rebates, and guaranteed rebates were evaluated over a 6-year contract period, with scenarios reflecting different VOE criteria and treatment durability.

RESULTS:

The average annual SoC cost for severe SCD patients (N = 138) was US$45,941 (SD US$59,653), with higher costs associated with more frequent VOEs. Gene therapies exa-cel and lovo-cel, with one-off list prices of US$2.2 million and US$3.1 million, respectively, exhibited high upfront costs, resulting in a negative cumulative balance averaging - US$2.11 million for exa-cel and - US$3.00 million for lovo-cel per patient over 6 years compared with SoC. Outcome-based rebates could potentially save Medicaid approximately US$260K (uncertainty interval 88K-772K) per patient on average for exa-cel and US$367K (uncertainty interval 122K-1111K) for lovo-cel after they pay the full up-front cost. Volume-based and guaranteed rebates also offered potential savings but varied in impact based on contract duration and effectiveness of gene therapy.

CONCLUSIONS:

The study highlights critical considerations for Medicaid in negotiating OBAs for SCD gene therapies. Achieving budget neutrality over 6 years is unlikely due to low SoC costs. However, payment models can enhance value-based spending by linking high therapy costs and potential rebates to the health gains these treatments may offer. OBAs offer offsets contingent on therapy effectiveness durability and contract terms (such as length and price), while varying eligibility criteria impact budgets and outcomes. Medicaid real-world data is crucial for navigating complexities in defining eligible populations and structuring OBAs.

2025-05-01·ADVANCES IN THERAPY

Impact of Different Definitions of Vaso-Occlusion on Efficacy Assessments in Sickle Cell Disease Clinical Trials

Review

作者: Xuan, Fengjuan ; Imren, Suzan ; Eckrich, Michael J ; Li, Nanxin ; Locatelli, Franco ; Grupp, Stephan A ; Frangoul, Haydar

INTRODUCTION:

Patients with sickle cell disease (SCD) experience recurrent, severe pain events due to vaso-occlusion. Eliminating these acute pain events is a key outcome in SCD clinical trials; however, the definition of a vaso-occlusive crisis (VOC) or a vaso-occlusive event (VOE) has not been consistently applied, hampering comparisons of treatment efficacy between different therapeutic approaches. We have examined the degree to which differing definitions of vaso-occlusion in clinical trial endpoints impact efficacy outcomes.

METHODS:

Descriptions of clinical endpoints related to vaso-occlusion and pain events were reviewed from trials of exagamglogene autotemcel (exa-cel), lovotibeglogene autotemcel (lovo-cel), renizgamglogene autogedtemcel (reni-cel), hydroxyurea, L-glutamine, voxelotor, and crizanlizumab. Patient-level data from the published exa-cel Phase 3 pivotal trial (CLIMB SCD-121; data cut 14 Jun 2023) was used to evaluate efficacy outcomes based on differing endpoint definitions of vaso-occlusion.

RESULTS:

In the seven clinical trials reviewed, definitions of vaso-occlusion and/or pain events varied by care setting, duration of care, treatments used, and associated complications, with the frequency and duration of medical facility visits for acute pain events being most dissimilar between trials. Definitions of severe VOCs (exa-cel), VOC (voxelotor), and sickle cell-related pain crises (SCPCs; crizanlizumab and L-glutamine) included pain events requiring a medical facility visit of any duration, whereas the definition of painful crises (hydroxyurea) required a medical facility visit of > 4 h and the definition of severe vaso-occlusive events (VOEs; lovo-cel and reni-cel) required a hospital or emergency room (ER) observation unit visit lasting ≥ 24 h or ≥ 2 visits to a day unit or ER over a 72-h period. Based on the definition of severe VOCs, 29/30 patients [96.7%; 95% confidence interval (CI): 82.8, 99.9] in the CLIMB SCD-121 trial were considered free from severe VOCs for ≥ 12 consecutive months, whereas when the severe VOEs definition was applied to the same data, all patients (30/30; 100.0%; 95% CI: 88.4, 100.0) were considered free from severe VOEs for ≥ 12 consecutive months.

CONCLUSION:

Differences exist in definitions of vaso-occlusion and pain events used in SCD clinical trials. Severe VOCs (exa-cel), VOC (voxelotor), and SCPCs (crizanlizumab and L-glutamine) were more broadly inclusive than severe VOEs (lovo-cel and reni-cel) or painful crisis (hydroxyurea). Clinically, these differences resulted in differing numbers of patients being considered free from vaso-occlusion pain events, underscoring the challenge in comparing frequencies of pain events across SCD clinical trials.

2024-12-01·CLINICAL PHARMACOLOGY & THERAPEUTICS

Infrequent Resolution of Vaso‐Occlusive Crises in Routine Clinical Care Among Patients Mimicking the Exa‐Cel Trial Population: A Cohort Study of Medicaid Enrollees

Article

作者: Beukelman, Timothy ; Mahesri, Mufaddal ; Titievsky, Lina ; Desai, Rishi J. ; Zhang, Lanju ; Lee, Su Been ; Imren, Suzan ; Levin, Raisa

The CRISPR‐based gene editing therapy exagamglogene autotemcel (exa‐cel) recently received FDA approval for patients with severe sickle cell disease (SCD). The approval was based on a phase III trial (CLIMB SCD 121), which showed 97% efficacy of this treatment in eliminating vaso occlusive crises (VOCs) for 12 consecutive months. To help contextualize results from this trial, we aimed to investigate the proportion of patients with severe SCD who remain VOC‐free for a 1‐year period in routine clinical care. Using Medicaid claims data (2000–2018), we identified a cohort of patients, 12–35 years old with severe SCD, defined by ≥ 2 VOCs per year for 2 consecutive years, who met other exa‐cel trial inclusion criteria to mimic a trial‐like population. A VOC was identified using ICD diagnosis codes during hospitalization and ER visits. The primary outcome was the proportion of patients with no VOCs during a 1‐year follow‐up. A total of 7,425 patients with severe SCD [mean (SD) age: 20.5 (6.0) years, 54.6% females, 84% African Americans], had a mean of 5.2 VOCs, 5.1 ER visits and 3.5 hospitalizations per year during the baseline period. The proportion of patients with no VOCs during the 1‐year follow‐up was 7.7% (95% confidence interval: 7.1%–8.3%). In conclusion, less than one in 12 patients with severe SCD achieved VOC‐free status within 1 year in routine clinical care. These findings suggest that the high efficacy observed for exa‐cel in the trial, if replicated in routine clinical care, could translate into a significant public health impact.

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项与 Exagamglogene Autotemcel 相关的新闻（医药）

2025-05-22

·CPHI制药在线

国产siRNA疗法“出海”再下一城！靖因药业与CRISPRT超8.9亿美元合作

关注并星标CPHI制药在线5月20日，中国生物技术公司靖因药业与基因编辑领域领军企业CRISPR Therapeutics正式建立战略合作伙伴关系，双方将联合开发并推动下一代长效小干扰RNA疗法SRSD107的商业化进程，该药物主要用于血栓及血栓栓塞性疾病的治疗。根据协议条款，靖因药业将获得CRISPR支付的9500万美元首期款项，并有权在后续研发及商业化进程中获取最高8亿美元的里程碑付款，使合作总金额突破8.95亿美元。图源：靖因药业官网靖因药业作为专注于siRNA疗法开发的临床阶段生物技术公司，凭借其自主知识产权的递送技术和靶点发现能力，已在心血管代谢疾病领域布局了多款管线。而CRISPR Therapeutics作为基因编辑领域的全球先驱，拥有成熟的基因疗法开发经验及全球化商业化能力，尤其在心血管疾病领域，其靶向ANGPTL3的CTX310项目已取得积极进展。根据协议，CRISPR将支付9500万美元首付款，后续靖因药业还有资格获得超过8亿美元的里程碑付款及销售分成。双方将以50:50的比例分担开发成本并共享利润，CRISPR负责美国市场的商业化，靖因则主导大中华区市场。协议还允许CRISPR在未来提名最多两个siRNA靶点，并主导后续开发，靖因可通过里程碑和销售分成持续获益。这样一来，既规避了传统License-out交易中本土企业后续参与度不足的风险，又通过分工协作加速了全球化进程。01SRSD107为何能成为“同类最佳”候选药物？作为靖因药业自主研发的创新药物，SRSD107是一款靶向凝血因子XI的siRNA疗法。其核心作用机制通过特异性抑制FXI蛋白表达，阻断内源性凝血途径的异常激活，在显著降低血栓形成风险的同时，有效减少出血并发症的发生。临床前研究表明，单次皮下注射SRSD107即可实现FXI表达近100%的抑制效果，且药效持续时间长达6个月，期间未观察到具有临床意义的出血风险。这种独特优势使其在抗凝治疗领域展现出差异化竞争力，特别适用于心房颤动、静脉血栓栓塞症及肿瘤相关血栓等高危患者群体。SRSD107的突破性价值在于其靶点选择的创新性。传统抗凝药物如华法林或新型口服抗凝药主要针对凝血因子Xa，虽能有效预防血栓形成，但存在较高的出血风险且需每日用药；而凝血因子XI作为内源性凝血途径的关键调控节点，在病理性血栓形成中发挥核心作用，但对正常生理止血功能影响较小，因此靶向FXI可实现“精准抗栓而不影响凝血”的治疗效果。哈佛医学院副教授Christian T. Ruff评论指出，SRSD107兼具低出血风险、半年超长药效及无肾脏代谢负担的特性，使其在现有治疗手段中形成显著竞争优势。在临床开发层面，SRSD107的Ⅰ期试验已于2024年完成全部受试者入组，初步安全性数据表现优异。2025年美国心脏病学会年会上披露的Ⅰ期研究结果，进一步验证了其疗效持久性和耐受性，为Ⅱ期临床试验的启动奠定了坚实基础。当前Ⅱ期研究聚焦于膝关节置换术后患者的静脉血栓栓塞症预防，这一适应症选择既契合临床未满足需求，骨科手术患者常因出血风险限制抗凝药物使用，也为后续拓展至更广泛患者群体提供了剂量优化依据。对靖因药业而言，此次合作是其全球化战略的关键里程碑。成立于2021年的靖因药业，通过中美双研发布局已构建起以siRNA技术为核心的心血管疾病管线，包括针对高脂蛋白血症的SRSD216和血脂异常的SRSD101。与CRISPR的战略合作不仅带来近1.5亿美元的即时资金注入，更通过开发成本共担机制有效降低了后续临床投入风险，同时借助CRISPR的全球网络加速产品国际化进程。对CRISPR Therapeutics而言，此次合作标志着其向非基因编辑治疗领域的战略延伸。尽管该公司以CRISPR/Cas9基因编辑技术闻名，其首款基因疗法CASGEVY®已获批治疗镰状细胞病和β地中海贫血，但近年来其研发管线正积极向心血管领域拓展。引入SRSD107不仅填补了抗凝治疗领域的空白，更可探索siRNA长效特性与基因编辑技术的协同潜力，例如通过联合用药实现更持久的治疗效果。02siRNA赛道为何成为跨国药企“必争之地”？siRNA（小干扰RNA）通过精准沉默疾病相关基因表达，具有长效性、高特异性等优势，近年来在肝靶向疾病中屡获突破。再者，血栓性疾病领域存在巨大未满足需求，全球约四分之一死亡与血栓相关，而现有抗凝药物普遍面临出血风险与用药频率的平衡难题。SRSD107若成功上市，不仅可能成为首个长效FXI抑制剂，更将推动抗凝治疗从“每日服药”迈向“半年一针”的突破。这一前景也解释了为何CRISPR愿意以近10亿美元押注。尽管前景可期，SRSD107仍需应对多重挑战：Ⅱ期及后续试验需在复杂患者群体（如肿瘤合并症或肾功能不全患者）中进一步验证安全性；市场竞争日趋激烈，除Alnylam外，拜耳与Ionis联合开发的FXI反义寡核苷酸药物也已进入临床阶段；此外，siRNA药物的生产成本及当前皮下给药方式可能影响患者依从性，未来口服剂型的开发将成为关键突破口。从长远发展来看，这场跨越太平洋的医药创新联盟，不仅是资本与技术的深度融合，更是全球生物医药产业分工重构的典型缩影。它既展现了中国创新药企在前沿技术领域的突破能力，也反映了跨国药企对差异化创新管线的迫切需求。随着SRSD107临床开发的持续推进，此次合作或将成siRNA疗法在心血管领域落地的关键节点，同时为中国生物技术企业的全球化路径提供重要借鉴。参考来源： [1]靖因药业官网新闻 [2]Yue P, Qu E, Pan J, et al. A Phase 1, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics,and Pharmacodynamics of Subcutaneously Administered SRSD107 in Healthy Subjects[J]. Blood, 2024, 144: 4009.END【企业推荐】智药研习社直播预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

引进/卖出siRNA基因疗法临床申请临床1期

2025-05-21

·医药笔记

9亿美元：靖因药业创新siRNA疗法授权给CRISPR

-该合作将双方在研发与产业化方面的互补能力相结合，共同开发并商业化下一代长效Factor XI（FXI）靶向小干扰RNA（siRNA）疗法SRSD107，用于治疗血栓及血栓栓塞性疾病 --根据协议条款，靖因药业将获得CRISPR Therapeutics（纳斯达克股票代码：CRSP）支付的9500万美元现金及现金等价物作为首付款，并有资格获得超8亿美元的预付款和里程碑付款。双方将以50-50的成本和利润分摊机制共同开发SRSD107。此外，协议还授予CRISPR Therapeutics在未来独家引进最多两个额外siRNA项目的优先授权权利 -NEWS美国圣地亚哥、中国上海、瑞士楚格及美国波士顿，2025年5月20日——靖因药业是一家处于临床阶段、专注于开发面向全球市场创新小干扰RNA（siRNA）疗法的生物技术公司；CRISPR Therapeutics（纳斯达克股票代码：CRSP）是一家专注于为严重疾病开发变革性基因疗法的生物制药公司。今日，双方宣布达成战略合作伙伴关系，将携手推进siRNA疗法的联合开发与商业化进程。靖因药业执行董事兼首席执行官冀群升博士“我们非常高兴与CRISPR达成此次合作。CRISPR Therapeutics是基因疗法开发领域公认的全球领导者。血栓性疾病存在大量未被满足的医疗需求，SRSD107展示的令人鼓舞的1期临床数据，进一步验证了其作为靶向凝血因子XI（FXI）同类最佳疗法的潜力。靖因药业致力于为全球患者提供创新治疗方案。此次合作将充分发挥双方优势，携手加速新一代siRNA疗法的全球开发与临床转化。”CRISPR Therapeutics董事长兼首席执行官Samarth Kulkarni博士“我们很高兴与靖因药业建立合作关系，并在近期公布的CTX310项目（靶向ANGPTL3）令人振奋的顶线数据基础上，进一步拓展我们在心血管疾病领域的管线布局。凝血因子XI是一个创新且极具吸引力的靶点，在治疗影响全球数以百万计患者的血栓性疾病方面展现出巨大潜力。SRSD107有望成为同类最佳疗法，凭借更低的给药频率和更优的临床获益，为临床治疗带来重大突破。靖因药业在siRNA平台方面的前沿技术与我们现有的研发能力高度互补，进一步丰富了我们的治疗技术平台，助力我们开发更广泛的变革性基因疗法。”TIMI研究组资深研究员、布里格姆妇科医院心脏病科主任、哈佛医学院副教授Christian T. Ruff医学博士“由于心血管疾病、恶性肿瘤、和高凝状态等基础疾病的存在，大量患者面临潜在的致死性血栓栓塞性事件风险。其中相当一部分患者由于担忧出血风险或用药依从性问题，未能获得治疗或充分治疗。SRSD107有望成为一款具有差异化优势的疗法，其特点包括出血风险更低、给药频率更低，患者依从性更高、无肾脏清除或药物相互作用担忧、并且具备更佳的可逆性，从而进一步降低出血风险的可能性。这些优势使其有望在现有疗法及靶向FXI其它疗法中脱颖而出。”SRSD107是一款新一代的长效siRNA疗法，旨在选择性抑制凝血因子XI（FXI）。FXI靶点在病理性血栓形成中起关键作用，但对正常止血功能的影响较小。通过靶向FXI，SRSD107有望在降低血栓事件发生的同时，显著减少出血风险，展现出有别与凝血因子X活性（FXa）抑制剂的治疗优势。SRSD107的潜在适应症广泛，包括房颤、静脉血栓栓塞症（VTE）、肿瘤相关性血栓、接受血液透析的终末期肾病患者，以及因出血风险限制现有治疗手段的重大骨科手术人群。目前，SRSD107已完成两项1期临床试验，结果显示单次给药安全性且耐受性良好。相关研究成果已在2025年美国心脏病学会（ACC）年会和2024年美国血液学会(ASH)年会上发布。SRSD107的2期临床试验正在启动，旨在评估其在膝关节置换术患者中预防静脉血栓栓塞症（VTE）的安全性和有效性。该研究将为确认其抗凝临床获益及后续关键性试验的剂量选择提供临床科学依据。双方将以50:50的成本与利润分成模式，共同推进SRSD107的开发。根据协议，CRISPR将负责该产品在美国的商业化，靖因药业则负责大中华区市场。此外，CRISPR Therapeutics拥有提名最多两个siRNA靶点的权利，并可选择主导后续的临床开发与商业化。靖因药业将有资格获得与项目进展挂钩的里程碑付款、附带条件的激励付款，以及按销售额分级计算的版税收入。关于血管栓塞血栓形成是血管内限制血液流动的血凝块，可发生在动脉或静脉循环中，是大多数心肌梗死、缺血性脑卒中和静脉血栓栓塞症（VTE）的共同病理基础。全球有四分之一的人死于血栓栓塞引发的疾病1。关于SRSD107注射液SRSD107注射液是一款靖因药业拥有自主知识产权的双链小干扰核酸（siRNA）药物。通过特异性肝靶向人凝血因子XI（FXI ）mRNA，抑制FXI的蛋白表达，阻断内源性凝血途径的激活，从而达到抗凝血作用。临床前试验数据显示，单次皮下注射SRSD107，可降低外周血FXI浓度近100%，且持续时间可长达半年，同时未见出血。SRSD107兼具强效持久作用和良好的安全性，有望成为潜在的同类首创（First-in Class）和同类最佳（Best-in-Class）新一代更安全的抗凝药物。关于靖因药业靖因药业 (Sirius Therapeutics) 是一家临床阶段的生物技术公司，以人类健康福祉为使命，致力开发颠覆慢病防治的siRNA新疗法的领军者。目前已进入临床开发阶段的产品包括用于治疗血栓栓塞性疾病的SRSD107，高脂蛋白(a)的SRSD216，和血脂异常的SRSD101。成立于2021年，由国际卓越的管理团队和全球知名医疗健康投资机构孵化。公司采取国际化的战略定位，汇聚中美两地在小核酸疗法领域的人才和资源的优势，建立了以美国为源头创新发现中心，中国为全球转化医学中心的布局。利用其小核酸药物研发核心技术平台，开发了多个具有同类首创或同类最佳潜质的差异化全球竞争优势的产品管线。公司已累计融资近1.5亿美元。欲了解更多信息，请访问www.siriusrna.com.关于CRISPR Therapeutics自十多年前成立以来，CRISPR Therapeutics已从一家致力于推进基因编辑计划的研究型公司发展成为一家行业领导者，并庆祝了全球首个CRISPR基因疗法获批的历史性时刻。该公司拥有多元化的产品候选组合，涵盖广泛的疾病领域，包括血红蛋白病、肿瘤学、再生医学、心血管疾病、自身免疫疾病和罕见病。2018年，CRISPR Therapeutics将首个CRISPR/Cas9基因编辑疗法推进临床，用于研究镰状细胞病和输血依赖性β地中海贫血的治疗。自2023年底起，CASGEVY®（exagamglogene autotemcel [exa-cel]）在多个国家获批，用于治疗符合条件的镰状细胞病或输血依赖性β地中海贫血患者。诺贝尔奖得主的CRISPR技术彻底改变了生物医学研究，代表了一种经过临床验证的强大方法，具有潜力创造一类全新的、可能具有变革性的药物。为了加速和扩大其努力，CRISPR Therapeutics与Vertex Pharmaceuticals等领先公司建立了战略合作伙伴关系。CRISPR Therapeutics AG总部位于瑞士楚格，其全资子公司CRISPR Therapeutics, Inc.位于美国，研发业务则设在美国马萨诸塞州波士顿和加利福尼亚州旧金山。欲了解更多信息，请访问www.crisprtx.com。引用文献：1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380, 2095-1128.+86 21 61207756 info@siriusrna.com媒体联系人：+86 21 61207756 info@siriusrna.com

siRNA引进/卖出基因疗法临床1期临床申请

2025-05-20

·PipelineReview

CRISPR Therapeutics and Sirius Therapeutics Announce Multi-Target Collaboration to Develop Novel siRNA Therapies

-Collaboration brings together complementary capabilities to co-develop and co-commercialize SRSD107, a next generation, long-acting Factor XI (FXI) small interfering RNA (siRNA) for the treatment of thromboembolic disorders- -SRSD107 demonstrated peak reductions in FXI activity >93% and increases in activated partial thromboplastin time (aPTT) >2x with maintained efficacy up to 6 months post-dosing in a Phase 1 clinical trial- -Under the agreement, CRISPR Therapeutics will make an upfront payment of $25 million in cash and $70 million in equity to Sirius Therapeutics; CRISPR Therapeutics also has rights to exclusively license up to two additional siRNA programs- -Expands CRISPR’s therapeutic toolkit to develop a broader range of transformative gene-based medicines in addition to the gene-editing programs in the clinic- ZUG, Switzerland and BOSTON, MA, USA and SAN DIEGO, CA, USA and SHANGHAI, China I May 19, 2025 I CRISPR Therapeutics (NASDAQ: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, and Sirius Therapeutics, a clinical stage biotech company developing innovative small interfering RNA (siRNA) therapies for global markets, today announced a strategic partnership to develop and commercialize siRNA therapies. “We are excited to partner with Sirius, and broaden our cardiovascular medicine portfolio, on the heels of promising top-line data that we recently shared for CTX310, which targets ANGPTL3,” said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics. “Coagulation Factor XI represents an innovative and highly compelling target for treating thrombotic diseases that affect millions worldwide. SRSD107, which targets Factor XI, has the potential to be a best-in-class therapy, offering infrequent dosing and improved patient outcomes. Sirius’ siRNA platform complements our existing capabilities and expands our therapeutic toolkit, enabling us to develop a broader range of transformative gene-based medicines.” “We are pleased to collaborate with CRISPR Therapeutics, a recognized leader in the development of gene-based medicines,” said Qunsheng Ji, MD, Ph.D. Chief Executive Officer of Sirius Therapeutics. “Thrombotic diseases represent a significant unmet need, and our promising Phase 1 data highlights the potential of SRSD107 as a best-in-class Factor XI-targeted therapy. Sirius is committed to addressing the needs of these patients, as we work with CRISPR Therapeutics to advance novel siRNA therapies globally.” “There is a large population of patients who are at risk for potentially life-threatening thromboembolic events due to underlying co-morbid diseases such as malignancy, cardiovascular disease, and hyper-coagulability. A significant percentage of these patients are inadequately treated due to concerns for bleeding risk, or challenges with compliance,” said Christian T. Ruff, M.D., M.P.H., senior investigator of TIMI Group, director General Cardiology, Brigham and Women’s Hospital, and associate professor, Harvard Medical School. “SRSD107 offers the potential for a therapy with lower bleeding risk, infrequent dosing for better compliance, without concerns for renal clearance or drug interactions, and reversibility to further mitigate bleeding risks that could be differentiated from currently available therapies and other Factor XI modalities.” SRSD107 is a next generation, long-acting siRNA designed to selectively inhibit Factor XI (FXI), a key driver of pathological thrombosis with minimal impact on normal hemostasis. By targeting FXI, SRSD107 aims to reduce thrombotic events while minimizing the risk of bleeding – representing a differentiated approach compared to Factor Xa inhibitors. In addition, SRSD107 may offer the potential for reversibility not observed with other anti-Factor XI modalities. The addressable population includes patients with atrial fibrillation, venous thromboembolism (VTE), cancer-associated thrombosis, chronic Coronary Artery Disease (CAD), chronic Peripheral Vascular Disease (PVD), end-stage renal disease requiring hemodialysis, and patients undergoing major orthopedic surgery, where bleeding risk limits existing therapies. The clinical program for SRSD107 includes two promising Phase 1 clinical trials, where single doses of SRSD107 were found to be safe and well tolerated. In addition, SRSD107 demonstrated robust pharmacodynamic effects, including reductions of over 93% in FXI levels and FXI activity (FXIa), along with more than a twofold increase in activated partial thromboplastin time (aPTT) relative to baseline. These effects were sustained, with responses maintained for up to 6 months post-dosing. SRSD107 has the potential to be a best-in-class FXI inhibitor, showing deep reductions in FXI via semi-annual subcutaneous injection. Results from the Phase 1 trials were presented at both the 2025 Annual Scientific Sessions of the American College of Cardiology and the 2024 Annual Meeting of the American Society of Hematology. Figure 1. SRSD107 Phase 1 Clinical Results: Sustained, dose-dependent pharmacodynamic response to therapy A Phase 2 clinical trial of SRSD107 is being initiated to evaluate its safety and efficacy for the prevention of VTE in patients undergoing total knee arthroplasty. The trial aims to confirm the anticoagulant benefits of SRSD107 and to inform dose selection for future pivotal trials. Collaboration Details Under the terms of the agreement, CRISPR Therapeutics will make an upfront payment of $25 million in cash and $70 million in equity to Sirius Therapeutics. The companies will jointly develop SRSD107 under a 50-50 cost and profit-sharing structure. CRISPR Therapeutics will lead commercialization in the U.S., while Sirius will be responsible for commercialization in Greater China. Additionally, CRISPR Therapeutics will have the option to nominate up to two siRNA targets for research and development. For each target, CRISPR Therapeutics will fund research and retain opt-in rights to lead clinical development and commercialization. Sirius will be eligible to receive milestone payments, as well as tiered royalties ranging from high single to low-double digits. About CRISPR Therapeutics Since its inception over a decade ago, CRISPR Therapeutics has evolved from a research-stage company advancing gene editing programs into a leader that celebrated the historic approval of the first-ever CRISPR-based therapy. The Company has a diverse portfolio of product candidates across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine, cardiovascular, autoimmune, and rare diseases. In 2018, CRISPR Therapeutics advanced the first-ever CRISPR/Cas9 gene-edited therapy into the clinic to investigate the treatment of sickle cell disease and transfusion-dependent beta thalassemia. Beginning in late 2023, CASGEVY ® (exagamglogene autotemcel [exa-cel]) was approved in several countries to treat eligible patients with either of these conditions. The Nobel Prize-winning CRISPR technology has revolutionized biomedical research and represents a powerful, clinically validated approach with the potential to create a new class of potentially transformative medicines. To accelerate and expand its efforts, CRISPR Therapeutics has formed strategic partnerships with leading companies 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. To learn more, visit www.crisprtx.com . CRISPR THERAPEUTICS ® standard character mark and design logo, CTX310™ and CTX320™ are trademarks and registered trademarks of CRISPR Therapeutics AG. CASGEVY ® and the CASGEVY logo are registered trademarks of Vertex Pharmaceuticals Incorporated. All other trademarks and registered trademarks are the property of their respective owners. About Thromboembolic Disorders Thrombosis, or blood clot formation, is the common underlying mechanism of most cases of myocardial infarction, ischemic stroke, and venous thromboembolism. According to a trial in The Lancet 1 of regional and global mortality rates, thromboembolic disorders are estimated to cause as many as 1 in 4 deaths worldwide. About SRSD107 SRSD107 is a novel double-stranded small interfering ribonucleic acid (siRNA). SRSD107 specifically targets the human coagulation factor XI (FXI) mRNA and inhibits FXI protein expression, thereby blocking the intrinsic coagulation pathway and promoting anticoagulant/anti-thrombotic effects. SRSD107 has been engineered for the potential to enable twice-a-year dosing. About Sirius Therapeutics Sirius is a clinical stage biotech company developing innovative siRNA therapies for global markets. We are dedicated to discovering and developing new treatment options for cardiovascular and cerebrovascular disease and translating siRNA technology into transformative medicine for chronic disease patients. Sirius’s most advanced products are SRSD107 for the treatment of thromboembolic disorders, SRSD216 for the treatment of hyperlipoproteinemia, and SRSD101 for the treatment of dyslipidemia. Founded in 2021 by a world-class leadership team and investors, Sirius has established an innovation center in the United States and translational medicine center in China. Sirius has raised nearly US$150 million funding to date from OrbiMed, Creacion Ventures, Hankang Capital, Delos Capital, and BioTrack Capital. Learn more at www.siriusrna.com References: 1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380, 2095-1128. SOURCE: CRISPR Therapeutics

临床结果临床1期引进/卖出上市批准临床2期

100 项与 Exagamglogene Autotemcel 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	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
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	Vertex Pharmaceuticals, Inc.	2022-05-03
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	加拿大	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	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


ASH2024	N/A	镰状细胞血症	-	Exagamglogene autotemcel	糧鏇齋廠憲淵觸築醖夢(築簾壓範鑰網願醖廠鑰) = 52.2% 夢憲願夢鏇積鹽夢艱糧 (膚繭醖鬱艱網簾艱糧範 ) 更多	-	2024-12-09
ASH2024	N/A	输血依赖性地中海贫血	-	Exagamglogene autotemcel	糧繭範鑰憲製鹹襯鹹蓋(顧醖窪繭淵鬱積憲選壓) = 60.7% 蓋衊觸簾醖鹽齋願襯餘 (構廠鬱簾範築積廠選夢 ) 更多	-	2024-12-08
NEWS 人工标引	N/A	输血依赖性β地中海贫血 \| 镰状细胞血症	-	Casgevy (SCD)	糧網繭壓構鏇簾糧廠膚(齋鑰築鹽憲築顧築觸鏇) = 襯顧窪膚選鏇艱網鏇膚選壓夢繭艱齋築網餘範 (醖夢鹹獵齋夢鑰顧齋蓋 ) 更多	积极	2024-06-15
NEWS 人工标引	N/A	输血依赖性β地中海贫血 \| 镰状细胞血症	-	Casgevy (TDT)	蓋壓獵淵鹽蓋餘膚蓋艱(壓蓋夢鑰鑰壓遞憲積網) = 願淵淵築齋餘獵簾艱艱艱選選鏇繭廠衊願製窪 (遞鬱鏇鹽選鑰齋繭觸製 ) 更多	积极	2024-06-15
NCT03745287 (CLIMB SCD-121, EHA 12024 \| EHA 22024) 人工标引	临床3期	镰状细胞血症	46	Exagamglogene autotemcel	膚積鏇糧範築廠遞遞鬱(構艱糧壓壓鬱糧願壓選) = 廠鬱選襯廠構醖獵觸糧膚選蓋艱窪顧醖獵憲淵 (積構鹽艱窪廠觸襯醖簾, 79 ~ 99) 更多	积极	2024-05-14
NCT03655678 (CTX001-111 \| CLIMB THAL-111, EHA2024) 人工标引	临床3期	输血依赖性地中海贫血	24	Exagamglogene autotemcel	憲餘鏇範願鑰鹽蓋網鑰(糧鑰艱醖餘憲網鹽鹹壓) = 衊窪糧選膚製淵衊壓憲簾願觸築餘膚簾鑰網構 (蓋憲鏇齋廠製積簾憲淵, 0.21) 更多	积极	2024-05-14
NCT03745287 (CLIMB SCD-121, EHA 12024 \| EHA 22024) 人工标引	临床3期	镰状细胞血症	24	exa-cel	糧餘遞窪齋蓋選鬱願襯(積顧積簾觸鬱襯憲構鑰) = By month 6, EQ-5D-5L health utility US index score and EQ VAS score showed substantial improvements,which were maintained through month 24 (change at month 24 [n=17]: 0.13 [0.19]; minimal clinically important difference [MCID] 0.078 and 26.9 [22.6]; MCID 7 to 10, respectively). 蓋獵襯願網顧淵選觸膚 (艱繭顧鏇廠網齋餘構艱 ) 更多	积极	2024-05-14
NCT03655678 (CTX001-111, FDA) 人工标引	临床2/3期	输血依赖性β地中海贫血	52	CASGEVY	廠壓積製製齋遞觸鹽顧(夢艱製築繭繭艱醖築艱) = 簾鬱餘襯淵鑰蓋淵膚網襯製鏇襯鑰繭願範築製 (遞廠鹽築獵鏇鹹糧觸壓, 75.7 ~ 100) 更多	积极	2024-02-07
NCT03655678 (CLIMB THAL-111, Tandem Meetings ASTCT and CIBMTR2024) 人工标引	临床3期	输血依赖性β地中海贫血	44	Exagamglogene autotemcel	蓋衊繭糧願夢淵範製鹽(製範膚壓蓋膚積蓋鹽衊) = 壓餘鏇艱繭鏇觸繭艱簾獵壓淵襯選顧衊窪製襯 (廠窪獵鑰範廠簾鏇構窪 )	积极	2024-02-01
NCT03655678 (CLIMB THAL-111, ASH2023)	临床3期	输血依赖性地中海贫血	52	Exagamglogene autotemcel	簾鬱鹹衊觸廠鹽鹹構簾(夢鹽糧衊壓製觸願構壓) = 鏇構觸夢憲簾醖膚網繭範廠鑰鏇廠選繭廠鹹積 (網醖餘衊膚夢糧製膚膚 ) 更多	积极	2023-12-11
NCT03745287 (CLIMB SCD-121, ASH2023)	临床3期	镰状细胞血症	42	Exagamglogene autotemcel	選製襯選憲餘顧積醖繭(糧鏇鹽觸艱淵憲襯襯餘) = 觸鏇膚鏇簾醖壓築齋鏇遞憲積襯餘網獵醖範艱 (範齋餘襯範選鑰鹹艱簾, 75.1% ~ 99.9%) 更多	积极	2023-12-11