MAGNITUDE-2: a Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2001 in Participants with Hereditary Transthyretin Amyloidosis with Polyneuropathy (ATTRv-PN)

This study will be conducted to evaluate the efficacy and safety of a single dose of nexiguran ziclumeran (NTLA-2001) compared to placebo in participants with ATTRv-PN.

开始日期2024-11-22

申办/合作机构

Intellia Therapeutics, Inc.

[+1]

NCT06128629 / Recruiting临床3期

MAGNITUDE: a Phase 3, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2001 in Participants with Transthyretin Amyloidosis with Cardiomyopathy (ATTR-CM)

To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.

开始日期2023-12-13

申办/合作机构

Intellia Therapeutics, Inc.

[+1]

NCT04601051 / Active, not recruiting临床1期

Phase 1 Two-Part (Open-label, Single Ascending Dose (Part 1) and Open-label, Single Dose Expansion (Part 2)) Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM)

This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NTLA-2001 in participants with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and participants with hereditary transthyretin amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM)

开始日期2020-11-05

申办/合作机构

Intellia Therapeutics, Inc.

100 项与 Nexiguran ziclumeran 相关的临床结果

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100 项与 Nexiguran ziclumeran 相关的专利（医药）

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项与 Nexiguran ziclumeran 相关的文献（医药）

2023-10-02·Molecular pharmaceutics

Differences and Similarities of the Intravenously Administered Lipid Nanoparticles in Three Clinical Trials: Potential Linkage between Lipid Nanoparticles and Extracellular Vesicles

Review

作者: Suzuki, Yuta ; Katsurada, Yuri ; Hyodo, Kenji

Lipid nanoparticles (LNPs) are clinically validated drug-delivery carriers. However, clinical data on intravenously administered LNPs are limited compared with those on intramuscularly administered LNPs (mRNA vaccines against COVID-19). Here, we reviewed three clinically tested intravenously administered LNPs (patisiran, mRNA-1944, and NTLA-2001). We summarize the differences and similarities in their formulations, mechanisms of action, and pharmacokinetics profiles. In humans, patisiran and mRNA-1944 exhibited similar multiphasic pharmacokinetic profiles with a secondary peak in the RNA concentration. siRNA (patisiran) and mRNA (mRNA-1944) exhibited prolonged blood circulation and were detectable for more than 28 days after a single administration. We further summarize the basics of extracellular vesicles (EVs) and discuss the potential linkages between LNPs and EVs. This Review provides an understanding of the human clinical data of intravenous LNP formulations, which can be potentially explored to develop next-generation LNP-and EV-based drug delivery carriers.

2022-12-01·The American journal of cardiology

Overview of Current and Emerging Therapies for Amyloid Transthyretin Cardiomyopathy

Article

作者: Maurer, Mathew S

Recent efforts in basic science have elucidated the pathobiology of amyloid transthyretin (ATTR) amyloidosis, leading to the development of the first generation of transthyretin (TTR)-targeted therapies for this disease. Along with tafamidis, the first approved therapy for ATTR-cardiomyopathy (CM), several other agents are in late-stage clinical development for ATTR-CM. TTR-stabilizing and -silencing agents with various mechanisms target TTR, preventing disaggregation of tetrameric TTR, and subsequent misfolding of TTR and formation of amyloid fibrils in the myocardium. These agents, including the TTR-super-stabilizing agent acoramidis, TTR-silencing agents patisiran, vutrisiran, and eplontersen, and TTR gene silencing with clustered, regularly interspaced, short palindromic repeats and associated Cas9 endonuclease-based therapy NTLA-2001, are in varying stages of development. The nonsteroidal anti-inflammatory diflunisal has been shown to have TTR-stabilizing properties and may play a role off-label as treatment in selected patients, particularly allele carriers of TTR variants and patients unable to afford current therapies. Anti-amyloid treatments represent another strategy for treating patients with advanced ATTR amyloidosis. These agents are designed to bind to epitopes on amyloid fibril and extract amyloid by activation of macrophage-mediated phagocytosis addressing amyloid already deposited in organs and tissues. Since many patients with ATTR-CM present with advanced disease and the presence of significant amyloid burden in the heart, anti-amyloid therapy represents an important area of unmet treatment need. Various investigational anti-amyloid therapies are in early-stage clinical development.

2021-08-05·The New England journal of medicine1区 · 医学

CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis

1区 · 医学

Article

作者: Gane, Ed ; Gutstein, David E ; Boyd, Adam P ; McKee, Mark D ; Cehelsky, Jeffrey E ; Leonard, John ; Sepp-Lorenzino, Laura ; O'Connell, Daniel ; Soltys, Randy ; Harari, Olivier ; Phillips, Jonathan ; Fontana, Marianna ; Lebwohl, David ; Zambrowicz, Brian ; Murphy, Andrew ; Kao, Justin ; Amaral, Adam ; Kyratsous, Christos A ; Taubel, Jorg ; Walsh, Kathryn R ; Schiermeier, Andrew ; Xu, Yuanxin ; Seitzer, Jessica ; Gillmore, Julian D ; Wood, Kristy ; Maitland, Michael L

BACKGROUND:

Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum. It is based on the clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) system and comprises a lipid nanoparticle encapsulating messenger RNA for Cas9 protein and a single guide RNA targeting TTR.

METHODS:

After conducting preclinical in vitro and in vivo studies, we evaluated the safety and pharmacodynamic effects of single escalating doses of NTLA-2001 in six patients with hereditary ATTR amyloidosis with polyneuropathy, three in each of the two initial dose groups (0.1 mg per kilogram and 0.3 mg per kilogram), within an ongoing phase 1 clinical study.

RESULTS:

Preclinical studies showed durable knockout of TTR after a single dose. Serial assessments of safety during the first 28 days after infusion in patients revealed few adverse events, and those that did occur were mild in grade. Dose-dependent pharmacodynamic effects were observed. At day 28, the mean reduction from baseline in serum TTR protein concentration was 52% (range, 47 to 56) in the group that received a dose of 0.1 mg per kilogram and was 87% (range, 80 to 96) in the group that received a dose of 0.3 mg per kilogram.

CONCLUSIONS:

In a small group of patients with hereditary ATTR amyloidosis with polyneuropathy, administration of NTLA-2001 was associated with only mild adverse events and led to decreases in serum TTR protein concentrations through targeted knockout of TTR. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051.).

164

项与 Nexiguran ziclumeran 相关的新闻（医药）

2024-12-06

·药渡

【药渡药闻报告-创新药篇】-2024年第47期/总第168期

全球药物批准/研发动态 01 全球新药批准情况根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）全球（不含中国）共有4个新药获批上市。其中，NDA批准2个，新适应症批准2个，新制剂批准1个。与上个统计周期相比，本次减少2个批准新药。 11月27日，AOP Health宣布FDA已批准RapiblykTM（Landiolol）在医院重症监护环境中用于治疗严重的心脏病室上性心动过速（心房颤动和心房扑动）。Landiolol是一种超短效肾上腺素能受体拮抗剂，β1/β2选择性比为255，特点是起效快，心率迅速降低，而不会显着降低血压。研究数据显示：40-90%接受治疗的患者在大约10分钟内心率下降，而接受安慰剂的患者为0-11。在安慰剂对照临床试验中，9.9%的Landiolol治疗患者观察到不良事件，而安慰剂治疗患者观察到1%。 11月27日，Novartis宣布EC已批准Kisqali（Ribociclib）与芳香化酶抑制剂（AI）联合用于激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性、复发风险高的早期乳腺癌（EBC）患者的辅助治疗。Kisqali在三项III期试验中始终显示出具有统计学意义的总生存期获益：在HR+/HER2-晚期乳腺癌的一线绝经前患者中得分为5分；与Letrozole或Fulvestrant联合使用一线治疗HR+/HER2-晚期乳腺癌绝经后患者中获得了4分。全球（不含中国）新药批准情况（部分） 02 全球新药申报进展根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）全球（不含中国）共有5个新药申报上市。其中，NDA申报5个，BLA申报2个。与上次统计周期相比，本次增加1个NDA/BLA申报。 11月28日，Satsuma Pharmaceuticals宣布，FDA已接受其在研鼻腔喷雾剂STS101重新提交的新药申请（NDA），用于急性治疗伴或不伴先兆的偏头痛。分析显示，STS101在使用后超过2小时的所有时间点上表现出显著且持久的疗效（p<0.001）。此外，STS101在多个次要终点上也表现出显著且持久的抗偏头痛效果。 NDA/BLA申报（部分）根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）全球（不含中国）共有3个药物获监管机构特殊资格认定。其中，化学药2个，生物药1个。与上次统计周期相比，本次减少7个获监管机构特殊资格认定的药物。 11月25日，Intellia Therapeutics宣布FDA已授予Nexiguran ziclumeran（NEX-z，也称为NTLA-2001）再生医学高级疗法（RMAT）称号，用于治疗遗传性转甲状腺素蛋白（ATTR）淀粉样变性伴多发性神经病（ATTRv-PN）。Nex-z是一种基于CRISPR的体内研究性疗法，设计为单剂量治疗，以灭活TTR基因，从而阻止产生用于治疗ATTR淀粉样变性的TTR蛋白。中期I期临床数据显示，Nex-z的给药导致一致、深入和持久的TTR降低。 11月27日，Lin BioScience宣布LBS-007已获得FDA授予治疗急性髓系白血病的快速通道资格。LBS-007是一种天然的非ATP细胞周期抑制剂，靶向多种癌症。LBS-007通过阻断CDC7的激酶活性发挥作用，CDC7是癌细胞周期的关键调节因子，抑制CDC7会阻止肿瘤细胞的增殖并导致癌细胞死亡。LBS-007在临床前研究中显示出对白血病和多种实体瘤的非常有效的活性。监管机构特殊资格认定药物 03 全球新药研发进展根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）全球（不含中国）新药临床研发状态更新共计19条，涉及肿瘤、血液和淋巴疾病、心血管疾病、神经疾病以及感染类疾病等共计6个领域。其中，肿瘤疾病领域临床进展更新居各领域之首，为8条：化学药4条，生物药2条，细胞疗法2条。 11月26日，AstraZeneca宣布CAPItello-281临床III期试验的积极结果。分析显示，对于PTEN缺陷型转移性激素敏感性前列腺癌（mHSPC）患者，Truqap（Capivasertib）联合Abiraterone和雄激素剥夺疗法（ADT）与Abiraterone和ADT联合安慰剂相比，在放射学无进展生存期（rPFS）的主要终点方面表现出统计学上显著并具临床意义的改善。Truqap组合是被证实对这种特定亚型前列腺癌有益的首个AKT抑制剂组合。 11月28日，UroGen Pharma近日公布其所开发的Jelmyto（Mitomycin）的长期随访研究结果。分析显示，接受初次化学消融治疗并达到完全缓解（CR）的低级别上尿路尿路上皮癌（LG-UTUC）成人患者，其中位缓解持续时间（DOR）达近4年。在OLYMPUS试验中，达到初始完全缓解的41名患者中位随访时间为28.1个月，中位DOR为47.8个月。全球新药研发进展详情（部分） 04 全球医药交易事件本次统计周期（2024.11.23-11.29）全球（含中国）医药交易时间共计20起，涉及药物权益转让、公司并购等多起交易事件。全球医药交易时间汇总表（部分）国内药物批准/研发动态 01 国内新药批准情况根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）国内共有7个新药获NMPA批准上市。其中，NDA批准1个，BLA批准3个，新适应症批准2个，新制剂批准1个。与上次统计周期相比，本次增加4个NMPA批准新药。 11月21日，正大天晴自主研发1类创新药盐酸安罗替尼胶囊联合派安普利单抗注射液一线治疗晚期肝细胞癌的上市申请获得国家药品监督管理局药品审评中心受理。研究结果显示，试验组中位PFS为6.9个月，对照组为2.8个月，疾病进展或死亡风险显著降低47%；试验组中位OS为16.5个月，对照组为13.2个月，死亡风险显著降低31%。安罗替尼已获批上市或受理10个适应症，涵盖6大癌种，持续展现了其在抗血管生成治疗领域的广阔应用前景。 11月27日，国家药品监督管理局通过优先审评审批程序批准上海泽德曼医药科技有限公司申报的泽立美®（本维莫德）乳膏上市，该药用于治疗2岁以上儿童和成人特应性皮炎（湿疹）。泽立美®乳膏是一种非激素类外用药，是我国自主研发具有全新作用机制和靶点的创新药。中国关键性临床研究结果表明，泽立美®乳膏起效快、疗效高，特别是对儿童特应性皮炎疗效更好，并有良好的安全性。国内新药批准情况 02 国内新药临床默示许可进展根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）国内共有53个新药获临床默示许可，涉及83个受理号。其中，化学药33个，治疗用生物制品18个，预防用生物制品2个。与上次统计周期相比，本次增加36个临床默示许可获批受理号。本周国内新药临床默示许可进展（部分） 03 国内新药申报进展根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）国内共有8个新药申报上市，涉及14个受理号。其中，化药3个，治疗用生物制品5个。与上次统计周期相比，本次减少4个新药申报上市受理号。国内新药申报上市情况（部分）根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）国内共有35个新药申报临床，涉及51个受理号。其中，化学药17个，治疗用生物制品17个，预防用生物制品1个。与上次统计周期相比，本次增加3个临床申报受理号。国内新药临床申报情况（部分）根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）国内无药物获NMPA特殊资格认定。与上次统计周期相比，本次减少1个获监管机构特殊资格认定的药物。 04 国内新药研发进展根据药渡数据统计分析，本次统计周期（2024.11.23-11.29）国内新药临床研发状态更新共计2条，涉及心血管疾病和感染2个领域。其中，化学药1条，生物药1条。与上次统计周期相比，本次减少7条国内新药临床研发状态更新。近日，由锐正基因（苏州）有限公司自主研发的基因编辑药物ART001注册I期临床试验的转甲状腺素蛋白淀粉样变心肌病（ATTR-CM）首位受试者用药顺利完成。1年前确诊为ATTR-CM的患者本次用药后，有潜力终生只需用药一次即可停止病情进展甚至逆转和“治愈”疾病，给患者带来了新的希望。患者在用药及住院观察期间未见输注相关反应，已顺利出院，目前患者情况良好。 11月25日，爱科百发今日正式宣布其预防呼吸道合胞病毒（RSV）感染的全人源单克隆抗体注射液AK0610的I期临床研究已成功完成全部受试者入组和给药。AK0610具有独特的病毒结合位点和作用机制，对变异RSV病毒株可以保持高效中和活性。临床研究过程中未观察到与药物相关的严重不良事件，药代动力学达到预期药物有效保护浓度，初步验证了AK0610在健康受试者中的良好安全性，耐受性和人体药代动力学。国内新药研发进展（部分） 05 国内新药研发领域政策法规动态国家药监局海关总署关于增设云南省勐康、磨憨口岸为药材进口边境口岸的公告（2024年第147号）根据《中华人民共和国药品管理法》，经国务院批准，同意增设云南省勐康口岸、磨憨口岸（含磨憨铁路口岸）为药材进口边境口岸。现将有关事项公告如下：一、中药材可经由勐康口岸、磨憨口岸（含磨憨铁路口岸）进口。所进口的药材应当符合《进口药材管理办法》等有关规定。二、普洱市市场监督管理局为勐康口岸对应的口岸药品监督管理部门，昆明市市场监督管理局为磨憨口岸（含磨憨铁路口岸）对应的口岸药品监督管理部门，承担所对应口岸进口药材的登记备案、组织口岸检验并进行监督管理工作。三、云南省食品药品监督检验研究院为勐康口岸、磨憨口岸（含磨憨铁路口岸）对应的口岸药品检验机构，承担上述口岸进品药材的口岸检验工作。本公告自发布之日起施行。特此公告。 06 国内新药研发领域热点新闻今日九源基因在港交所上市，华东医药为最大股东今日，九源基因在港交所正式上市，共发行4539.88万股。经股权结构层层剥茧后发现，九源基因与华东医药紧密相连。李邦良为九源基因的创始人，也是华东医药的前董事长。正是在李邦良的带领下，中美华东与福士生物、台湾裕友建设、香港源裕投资共同设立九源基因。中美华东作为华东医药最重要的子公司，根据IPO前的股权结构，其持股占比21.06%，是九源基因目前最大的股东。因为这层关系，九源基因与华东医药在业务上也多有交叉。有华东医药这棵大树在背后撑着，九源基因能否高枕无忧？更多资讯，请阅读原文 AKT：泛癌种潜力靶点上市首年的AKT抑制剂Capivasertib（Truqap），2024年前三季度实现营收2.7亿美元，全年销量有望超4亿美元。 2023年11月，阿斯利康AKT抑制剂Capivasertib获FDA批准上市，与Fulvestrant（氟维司群）联合使用，用于治疗激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性、伴有一种或多种生物标志物改变（PIK3CA、AKT1或PTEN）的局部晚期或转移性乳腺癌成年患者。这是全球首款乳腺癌AKT抑制剂。 AKT是一种丝氨酸/苏氨酸激酶，是PI3K（磷脂酰肌醇3-激酶）信号通路中主要的下游效应分子之一。目前，多款AKT抑制剂正处于临床研发阶段，横跨乳腺癌、前列腺癌、卵巢癌等多个癌种，市场潜力非常可观。更多资讯，请阅读原文小D有话说为方便读者阅读及保存，我们将周报原文整理成了PDF版本，如需获取全文，可点击最上方蓝字，在药渡Daily公众号后台回复“1205周报”，即可下载。

上市批准临床3期申请上市

2024-11-30

·生物制药小编

体内CRISPR vs siRNA，同适应症同期非头对头比较

数据出来有一段时间了，由于该siRNA有给药周期长的特征，值得一比，但拖着没写主要原因是懒...另一个原因是虽然同适应症、同期，但人群不同，一个是患者，一个是健康人，所以终点也不相同，有点不太好比... 纠结一阵时间后，经过仔细思考，突然发现，拿健康人做试验才是真的牛，任何涉及基因工程改造的疗法（含理论上“精准”编辑的CRISPR，不限ex vivo和in vivo）基本不会拿健康人做实验，因为有潜在脱靶/突变风险，按照FDA法规还要随访十五年。比较完发现两者有点既生瑜何生亮的感觉... 要比较的CRISPR疗法是Intellia公司的Nexiguran Ziclumeran (nex-z, Also Known as NTLA-2001)，siRNA疗法是Alnylam公司的ALN-TTRsc04，所针对适应症都为转甲状腺素蛋白淀粉样变（Transthyretin Amyloidosis，ATTR）。 ATTR Amyloidosis是由TTR蛋白错误折叠并聚集引起的，会影响心脏、神经、消化道等，分为遗传性（hATTR）和野生型（wtATTR）两种。 ALN-TTRsc04 主要是通过沉默肝脏中变异和野生型 TTR（因为GalNAc主要就是靶向肝脏，对于疾病或技术不了的请先看Alnylam研发日材料，去年元旦假期翻译的，真是闲的...），来减少循环TTR的水平，阻止或清除组织淀粉样蛋白沉积，以延缓或改善症状。这个命名一看就是皮下注射。值得注意的是，ALN-TTRsc04开发基于IKARIA平台，旨在减少给药频率，达到每年一次，2年前研发日材料时定的目标是300mg/y，使TTR水平降低90%以上。 Nex-z通过LNP递送，单次静脉输注给药，直接失活野生和变异的TTR基因，从根本上减少TTR的产生开始对比先看ALN-TTRsc04，试验设计如下，健康人剂量递增，所以没有NT-proBNP，hs-Troponin T，或 6MWT这种指标，主要终点是安全性，单次给药，12个月评估期受试者基线特征 PK数据如下有效性数据，300mg组，能将TTR减少90%，维持半年左右，9个月的时候已经高于90%了，再往后有点继续上升。600mg和900mg目前只有6个月的数据安全性数据如下，感觉还行，不过高剂量组似乎有点肠胃炎，如果这是个问题的话，有可能300mg q6m?不是问题的话就600mg q12m或900mg q12m了再来看下CRISPR疗法，试验设计如下，有点不太好的是无对照组受试者基线特征血浆TTR的变化，TTR降低90%以上现在已经维持2年了（11位患者）有效性数据如下，都比较稳定，如果有对照组，该上升的上升，该下降的下降，图会更好看些近80%的受试者疾病稳定或改善 QoL也是稳定或改善呼吸方面的功能也保持稳定12个月影像学评估安全性方面，看起来比siRNA严重很多...39%的SAE，难不成是因为招募的ATTR-CM患者？还有一例患者因AE导致死亡，给药506天后死于缺血性心脏病，与治疗无关... 比较完毕个人感觉，CRISPR虽然是单次给药，但是任何对DNA的改造都有脱靶/突变风险，需要随访15年，而高比例SAE可能也会影响其应用。siRNA在疗效类似，安全性更优的前提下，只要能做到半年一次，竞争力就挺大了... 有个问题，如果拿siRNA治疗TDT，SCD会怎样？声明：本人不在研发一线，经常站着说话不腰疼，水平非常有限，错误不可避免，信息可能也非最新，欢迎批评指正。所有文章仅作个人笔记整理（所以作者几乎都是记事本，有时候为了开赞赏也用青盐记当作者名），非治疗方案推荐，也不构成任何投资建议。所有的观点和言论仅代表本人，与本人就职单位和曾就职单位无关。

基因疗法siRNA临床结果临床研究

2024-11-26

·GlobeNewswire-Health Care

Intellia Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to Nexiguran Ziclumeran (nex-z) for the Treatment of Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy

Nov. 25, 2024 -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to nexiguran ziclumeran (nex-z, also known as NTLA-2001) for the treatment of hereditary transthyretin (ATTR) amyloidosis with polyneuropathy (ATTRv-PN). Nex-z is an in vivo CRISPR-based investigational therapy designed as a single-dose treatment to inactivate the TTR gene and thereby prevent the production of TTR protein for the treatment of ATTR amyloidosis. Development and commercialization of nex-z is led by Intellia as part of a multi-target collaboration with Regeneron. “This RMAT designation underscores the transformative potential of nex-z, our investigational in vivo CRISPR-based gene editing therapy for those living with hereditary ATTR amyloidosis with polyneuropathy,” said Intellia President and Chief Executive Officer John Leonard, M.D. “It was granted following the FDA’s review of our compelling interim Phase 1 data that indicated our one-time treatment led to rapid, deep and durable TTR reduction, which is expected to halt and potentially reverse the disease. We look forward to working closely with the FDA to bring this potential paradigm-shifting therapy to patients as quickly as possible.” The RMAT designation was established under the 21st Century Cures Act to expedite the development and review of promising therapeutic candidates, including genetic therapies, that are intended to treat, modify, reverse or cure a serious or life-threatening disease. RMAT designation includes benefits, such as early interactions with the FDA, including discussions on surrogate or intermediate endpoints that could potentially support accelerated approval and satisfy post-approval requirements, and potential priority review of a product’s biologics license application (BLA). This RMAT designation is the third special regulatory designation received by Intellia for nex-z. Nex-z was also granted Orphan Drug Designation by the U.S. FDA and European Union Orphan Drug Designation by the European Commission. Based on Nobel Prize-winning CRISPR/Cas9 technology, nex-z has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis. Nex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein. Interim Phase 1 clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development and commercialization collaboration with Regeneron. Transthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive and fatal disease. Hereditary ATTR (ATTRv) amyloidosis occurs when a person is born with mutations in the TTR gene, which causes the liver to produce structurally abnormal transthyretin (TTR) protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system. ATTRv amyloidosis predominantly manifests as polyneuropathy (ATTRv-PN), which can lead to nerve damage, or cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some individuals without the genetic mutation produce non-mutated, or wild-type TTR proteins that become unstable over time, misfolding and aggregating in disease-causing amyloid deposits. This condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily affects the heart. There are an estimated 50,000 people worldwide living with ATTRv amyloidosis and between 200,000 and 500,000 people with ATTRwt amyloidosis. There is no known cure for ATTR amyloidosis and currently available medications are limited to slowing accumulation of misfolded TTR protein. Intellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. The company’s in vivo programs use CRISPR to enable precise editing of disease-causing genes directly inside the human body. Intellia’s ex vivo programs use CRISPR to engineer human cells outside the body for the treatment of cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its people, is helping set the standard for a new class of medicine. To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies. Learn more at intelliatx.com and follow us @intelliatx. The content above comes from the network. if any infringement, please contact us to modify.

孤儿药基因疗法

100 项与 Nexiguran ziclumeran 相关的药物交易

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研发状态

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
神经病	临床3期	新西兰	Intellia Therapeutics, Inc.	2024-11-22
多发性神经病	临床3期	新西兰	Intellia Therapeutics, Inc.	2024-11-22
转甲状腺素蛋白相关家族性淀粉样多神经病变	临床3期	新西兰	Intellia Therapeutics, Inc.	2024-11-22
甲状腺素运载蛋白淀粉样变心肌病	临床3期	美国	Intellia Therapeutics, Inc.	2023-12-13
甲状腺素运载蛋白淀粉样变心肌病	临床3期	美国	Regeneron Pharmaceuticals, Inc.	2023-12-13
甲状腺素运载蛋白淀粉样变心肌病	临床3期	阿根廷	Regeneron Pharmaceuticals, Inc.	2023-12-13
甲状腺素运载蛋白淀粉样变心肌病	临床3期	阿根廷	Intellia Therapeutics, Inc.	2023-12-13
甲状腺素运载蛋白淀粉样变心肌病	临床3期	澳大利亚	Regeneron Pharmaceuticals, Inc.	2023-12-13
甲状腺素运载蛋白淀粉样变心肌病	临床3期	澳大利亚	Intellia Therapeutics, Inc.	2023-12-13
甲状腺素运载蛋白淀粉样变心肌病	临床3期	加拿大	Regeneron Pharmaceuticals, Inc.	2023-12-13

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临床结果

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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


NCT04601051 (Literature) 人工标引	临床1期	甲状腺素运载蛋白淀粉样变心肌病	36	Nexiguran ziclumeran (nex-z)	蓋積蓋鑰窪憲觸廠選觸(鏇淵鹽顧蓋網鏇鏇鏇衊) = 襯選顧鹽襯選構構醖齋壓簾鏇鹹觸製構鏇繭夢 (膚積築鬱顧顧糧選夢鬱, -33 ~ 49) 更多	积极	2024-11-16
NCT04601051 (Biospace) 人工标引	临床1期	转甲状腺素运载蛋白淀粉样变性	62	NTLA-2001	膚網構範願鬱膚鏇壓鏇(範鏇鹽願蓋壓觸顧膚齋) = The most commonly reported adverse events were infusion-related reactions, which occurred in 38% of patients. The majority of adverse events, including infusion-related reactions, were Grade 1 or 2 in severity, transient and resolved spontaneously. Other adverse events that were reported in greater than 10% of patients included headache, diarrhea and back pain, and were all Grade 1 or 2. 構艱簾築膚膚簾網構憲 (膚壓鑰獵繭鹽選鏇獵壓 ) 更多	积极	2023-11-02
NCT04601051 (NTLA-2001, EASL2022)	临床1期	转甲状腺素运载蛋白淀粉样变性 TTR protein	14	NTLA-2001 0.3 mg/kg	網衊獵願願製積顧獵壓(網範鬱鏇範蓋夢鏇糧選) = Mild and transient infusion reactions were the most common adverse event with NTLA-2001 鹹夢襯製蓋齋製醖獵繭 (範製廠壓鬱觸鹽襯襯鏇 )	积极	2022-06-24
NCT04601051 (Pubmed \| Br Dent J \| N Engl J Med) 人工标引	临床1期	转甲状腺素运载蛋白淀粉样变性	6	NTLA-2001 (0.1 mg / kg)	餘壓醖艱築鏇鬱構廠膚(壓艱願鹽糧憲淵艱醖窪) = 鏇製鹽淵獵壓夢構齋獵構醖鹽鑰襯積顧膚築衊 (廠餘顧齋鏇廠艱構夢獵 )	积极	2021-08-05
NCT04601051 (Pubmed \| Br Dent J \| N Engl J Med) 人工标引	临床1期	转甲状腺素运载蛋白淀粉样变性	6	NTLA-2001 (0.3 mg / kg)	餘壓醖艱築鏇鬱構廠膚(壓艱願鹽糧憲淵艱醖窪) = 鏇鹹糧膚範鑰蓋顧糧壓構醖鹽鑰襯積顧膚築衊 (廠餘顧齋鏇廠艱構夢獵 )	积极	2021-08-05