An Open-label, Single-arm Treatment Study to Investigate the Safety and Tolerability of Switching From Emicizumab to Fitusiran Prophylaxis in Male Participants Aged ≥18 Years of Age With Severe Hemophilia A, With or Without Inhibitors

This is an exploratory, single group, Phase 1, 1-arm study to assess treatment with fitusiran prophylaxis after switching from emicizumab prophylaxis.
This study aims to evaluate the safety and tolerability of switching to fitusiran after a transition period from the last dose of emicizumab. The study will be conducted in male participants with severe hemophilia A, with or without inhibitors, aged ≥18 years, who were previously receiving emicizumab prophylaxis.
Study details include:
* The study duration will be up to approximately 28 months:
* There will be an approximately 2-month screening period.
* There will be a transition period before fitusiran treatment starts (pre-fitusiran treatment period)
* The fitusiran treatment duration will be up to 18-months (fitusiran treatment period)
* The antithrombin (AT) follow-up (FU) period will be up to 6 months after the last dose of fitusiran (during which the AT activity level will be monitored at approximately monthly intervals following the final fitusiran dose until AT activity levels return to at least 60%).
* The study site visits are scheduled at monthly/ every 2 months intervals of 28 days (4 weeks) / 56 days (8 weeks), respectively, during the fitusiran treatment period.

开始日期2024-03-01

申办/合作机构

Sanofi

CTR20230417

/ Active, not recruiting临床3期

一项在有或无凝血因子 VIII 或IX 抑制性抗体的≥12 岁重度 A 型或 B 型血友病男性受试者中评估fitusiran 预防治疗疗效和安全性的 III 期、单臂、多中心、多国、开放性、单向交叉的研究

主要目的：描述接受 fitusiran 预防治疗时治疗出血事件的频率。次要目的：评估 fitusiran 预防治疗与预防性标准治疗（SOC）相比的疗效；评估 fitusiran 预防治疗与按需 SOC 相比的疗效；描述接受 fitusiran 预防治疗时相对于接受 SOC 的以下特征：1）治疗自发性出血事件的频率2）治疗关节出血事件的频率3）年龄 ≥ 17 岁受试者的健康相关生活质量（HRQOL）；描述接受 fitusiran 治疗的受试者在 18 个月疗效期和 36 个月治疗期间的出血发作频率；描述 CFC/BPA 经体重校正的年化消耗量；描述 fitusiran 的安全性和耐受性。

开始日期2023-04-24

申办/合作机构

Sanofi-Aventis Recherche & Développement SA

[+2]

CTR20200294

/ Active, not recruiting临床3期

ATLAS-OLE:一项在存在或不存在凝血因子Ⅷ 或 ⅸ抑制性抗体的A或B型血友病患者中评估FITUSRAN的长期安全性和疗效的开放性研究

主要目的：确定fitusiran的长期安全性和耐受性特征。次要目的：1.通过评估以下指标的频率，确定fitusiran的长期疗效特征：出血,自发出血,靶关节出血；2.确定fitusiran对 ≥17 岁参加者的健康相关生活质量指标的影响特征。三级/探索性目的：表征fitusiran 的PD 效应;表征fitusiran 的药代动力学（PK）;表征fitusiran 的免疫原性;表征fitusiran 对以下患者报告结局的长期影响：● 参加者对fitusiran 的满意度● 参加者活动● 青少年（≥12 至<17 岁）的健康相关生活质量; 表征fitusiran 对因子浓缩物和BPA 的经体重校正的总消耗量的长期影响;表征fitusiran 对镇痛药用量的长期影响;表征fitusiran 对关节健康的长期影响;表征fitusiran 对参加者资源使用的长期影响.

开始日期2021-06-21

申办/合作机构

Genzyme Corp.

[+2]

100 项与芬妥司兰钠相关的临床结果

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项与芬妥司兰钠相关的文献（医药）

2025-04-30·Drug Discoveries and Therapeutics

Fitusiran: The first approved siRNA therapy for hemophilia <i>via</i> reducing plasma antithrombin levels

Review

作者: Lu, Daoran ; Dou, Fangzhou ; Gao, Jianjun

Hemophilia is a coagulation disorder caused by deficiencies in clotting factors and is primarily classified into hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency). Current treatment relies predominantly on replacement therapy, where patients receive clotting factor concentrates either episodically or prophylactically to achieve hemostasis or mitigate bleeding risks. Despite its efficacy, this approach presents limitations, including suboptimal treatment accessibility due to high costs, reduced patient compliance from frequent intravenous administration, and therapeutic failure in patients developing plasma inhibitors. These challenges underscore the need for novel therapeutics addressing unmet clinical demands. On March 28, 2025, the US Food and Drug Administration (FDA) approved fitusiran, a small interfering RNA (siRNA) therapeutic for hemophilia. This first-in-class agent demonstrates pan-hemophilia efficacy by targeting antithrombin to enhance thrombin activity, irrespective of factor VIII/IX deficiency status or plasma inhibitor presence. By pioneering a mechanism of antithrombin suppression, enabling sustained therapeutic action, and facilitating precision monitoring protocols, fitusiran has the potential to redefine hemophilia treatment paradigms.

2025-03-11·Blood Advances

Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B

Article

作者: Mangles, Sarah ; Kichou, Salim ; Chowdary, Pratima ; Feng, Liqi ; Forbes, Adam ; Lissitchkov, Toshko ; Menapace, Laurel A. ; Andersson, Shauna ; Ragni, Margaret V. ; Georgiev, Pencho ; Trinchero, Alice ; Hegemann, Inga ; Pipe, Steven W. ; Demissie, Marek

Abstract:

Fitusiran is an investigational small interfering RNA therapeutic that targets antithrombin (AT) to rebalance hemostasis in people with hemophilia. Here, we present the results of a completed phase 2 open-label extension study, which evaluated the long-term safety and efficacy of fitusiran in participants with moderate or severe hemophilia A or B, with or without inhibitors. Male participants who had completed the phase 1 study (ClinicalTrials.gov identifier: NCT02035605) were enrolled. Participants received monthly subcutaneous fitusiran (50 or 80 mg) under the original dose regimen until a voluntary dosing pause in 2020, after which the AT-based dose regimen was introduced, targeting the recommended AT activity levels of 15% to 35%. Thirty-four participants (hemophilia A, n = 27; hemophilia B, n = 7) were enrolled in the phase 2 study and treated with fitusiran for a median exposure of 4.1 years. Adverse events reported on the original and the AT-based dose regimen were consistent with the identified risks of fitusiran. After implementation of the AT-based dose regimen, there were no thrombotic events, and a reduction in the incidence of elevated transaminases and biliary events was reported. The observed median annualized bleed rate (ABR) on the AT-based dose regimen (0.87) was comparable with the ABR under the original dose regimen (0.70). Furthermore, fitusiran prophylaxis was associated with improved health-related quality of life compared with baseline and provided successful hemostatic control during surgical procedures and invasive interventions. Overall, fitusiran was well tolerated, and effective bleeding control was maintained on an AT-based dose regimen. This trial was registered at www.clinicaltrials.gov as #NCT02554773.

2025-02-01·SEMINARS IN THROMBOSIS AND HEMOSTASIS

Non-factor Therapies for Hemophilia: Achievements and Perspectives

Review

作者: Jiménez-Yuste, Victor

Abstract:

Non-factor replacement therapies (NFTs) have been developed to address the limitations of conventional replacement therapies, aiming to improve hemostasis and provide enhanced protection against bleeding episodes and long-term joint damage for patients both with and without inhibitors. Factor VIII (FVIII)-mimetic agents, such as emicizumab, have transformed the management of hemophilia A with inhibitors, offering a lower treatment burden and an effective alternative for those without inhibitors as well. Rebalancing agents, including anti-tissular factor pathway inhibitor agents (concizumab and marstacimab) and serpin inhibitors like fitusiran, have shown promising efficacy for patients with hemophilia B with inhibitors and other hemophilia subtypes. Administered subcutaneously, NFTs generate stable thrombin levels and feature a long half-life, which can shift severe hemophilia toward a milder phenotype. These therapies are effective regardless of inhibitor status and hold potential for application in other bleeding disorders. Evaluating the potential thrombotic risk after implementing mitigation measures, along with the development of anti-drug antibodies (ADAs), remain critical areas for further analysis. NFTs pose additional challenges due to their complex mechanism of action and the absence of a standardized laboratory assessment method. Unresolved issues include optimal management strategies for major surgeries and tailored approaches for safe use in older populations. This review highlights the progress and future potential of NFTs in treating persons with hemophilia.

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项与芬妥司兰钠相关的新闻（医药）

2025-06-09

·生物制品圈

siRNA 疗法突破肝脏局限，开启多器官靶向新时代

2025 年 6 月 9 日，随着多家药企在 RNA 干扰（RNAi）领域的持续突破，小干扰 RNA（siRNA）疗法正站在关键转折点。继 Alnylam 在肝脏靶向治疗中取得显著成功后，行业正全力攻克多器官递送难题，一场从 "肝脏专属" 到 "全身布局" 的技术革命已然拉开序幕。一、肝脏靶向的辉煌：Alnylam 奠定行业基石2025 年 3 月，Alnylam 再获两项 FDA 批准：Amvuttra 用于转甲状腺素蛋白介导的淀粉样变性，与赛诺菲合作的 Qfitlia 则针对血友病 A 和 B。这一成就延续了该公司的创新轨迹 ——2018 年，其首款 siRNA 药物 Onpattro 获批，标志着 RNAi 疗法从实验室走向临床的重大突破。回顾技术演进，1998 年 Craig Mello 发现 RNA 干扰机制，2002 年 Alnylam 成立，直至 2014 年 GalNAc 配体技术问世，才真正解决了 siRNA 的肝脏靶向难题。Onpattro 通过 GalNAc 偶联技术，首次实现了在肝脏细胞中特异性沉默致病基因，不仅缓解遗传性转甲状腺素蛋白淀粉样变性多发性神经病的症状，更实现了功能改善，被行业分析师 Myles Minter 称为 "革命性突破"。目前，Alnylam 已有多款药物获批，涵盖高胆固醇血症（与诺华合作的 Leqvio）、急性肝卟啉症（Givlaari）等领域。诺和诺德的 Rivfloza 也于 2023 年获批，共同构建了 siRNA 在肝脏疾病中的治疗版图。威廉・布莱尔高级分析师 Minter 指出："siRNA 在罕见病领域已展现变革性潜力，而更广泛适应症的突破才刚刚开始。"二、多器官靶向：从实验室到临床的突破尝试尽管现有 siRNA 疗法均聚焦肝脏，但多家药企已在非肝脏组织靶向中取得进展。Alnylam 首席技术官 Vasant Jadhav 表示，公司正攻关脑、脂肪、肺等组织的递送技术，其候选药物 mivelsiran 已进入 II 期临床试验，用于治疗脑淀粉样血管病，并启动阿尔茨海默病的 I 期研究。礼来的分子发现副总裁 Andrew Adams 强调，GalNAc 仍是目前最成功的靶向工具，但团队正探索脑靶向递送："一旦突破新组织的递送瓶颈，将开启类似肝脏靶向的适应症拓展浪潮。"Arrowhead Pharmaceuticals 的研究同样引人注目：其 siRNA 候选药物在小鼠实验中成功减少体脂并保留瘦肌肉，其中靶向脂肪细胞 ALK7 基因的疗法已启动早期临床；另一款靶向肺部的 ARO-RAGE 在哮喘患者中使目标蛋白水平降低 88%，展现出呼吸系统疾病的治疗潜力。三、技术边界与行业竞争格局siRNA 疗法仍面临固有挑战：无法完全敲除基因表达，仅能下调；且无法直接补充缺失蛋白。Jadhav 以 Givlaari 为例解释 workaround 策略：通过沉默代谢通路中上游的 GO 酶，降低急性肝卟啉症的毒性中间产物，而非直接修复突变酶。基因编辑技术的崛起也带来竞争压力。礼来的 Adams 指出，当 siRNA 长期数据证明敲低特定蛋白的安全性后，基因编辑可能成为永久性解决方案，如 Verve Therapeutics 已针对 PCSK9 基因开展编辑疗法的临床试验。但 Jadhav 强调 siRNA 的独特优势："兼具持久活性与可逆性，这是基因编辑无法同时实现的。"行业并购热潮反映了资本对 siRNA 的信心。2024 年 1 月，勃林格殷格翰与中国苏州瑞博生物达成 20 亿美元合作，开发非酒精性脂肪性肝炎（MASH）疗法；2025 年 5 月，GSK 以 12 亿美元收购 Boston Pharmaceuticals 的 FGF21 类似物，同样瞄准 MASH。据预测，到 2030 年 MASH 将影响 2700 万美国人，这类代谢疾病正成为 siRNA 的下一个战场。四、未来展望：技术迭代与市场扩容的双重机遇Minter 将 siRNA 的当前阶段形容为 "站在悬崖边缘"：一方面，肝脏靶向的成功奠定了坚实基础；另一方面，多器官递送的突破将开启黄金时代。Alnylam 设定了 2030 年 "靶向任意器官" 的目标，而礼来、Arrowhead 等企业的管线进展印证了这一愿景的可行性。从科学意义看，siRNA 不仅是药物开发的新工具，更重塑了基因调控的治疗逻辑 —— 通过 "基因开关" 而非传统小分子或抗体，实现更精准的疾病干预。随着递送技术的突破，神经系统、免疫系统等复杂疾病的治疗有望迎来革新。对患者而言，siRNA 的长效性（部分药物每半年给药一次）和高特异性，意味着更便捷的治疗方案和更少的副作用。而对行业来说，这场从肝脏到全身的技术跨越，可能催生数千亿美元的市场，重塑生物医药的竞争格局。站在 2025 年的技术临界点，siRNA 疗法的下一个十年注定充满挑战与机遇。正如 Minter 所言："未来五到十年，这个领域必将激动人心，我们正见证一场医学革命的序幕。" 当 Alnylam 等先驱者突破组织屏障，siRNA 或将成为继单克隆抗体、基因编辑之后，又一个改变疾病治疗范式的颠覆性技术。参考来源：https://www.biospace.com/drug-development/sirna-on-the-precipice-as-candidates-reach-beyond-the-liver识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

siRNA临床1期

2025-06-09

·BioSpace

siRNA on the Precipice as Candidates Reach Beyond the Liver

iStock, Love Employee As multiple companies vie to expand on Alnylam’s success in commercializing RNAi therapeutics, the pioneering company has set a goal of targeting small interfering RNA to any organ by 2030. In March, Alnylam chalked up two FDA approvals, for Amvuttra in transthyretin-mediated amyloidosis and, with Sanofi, Qfitlia in hemophilia A and B. Such approvals have become par for the course for Alnylam, leading multiple other companies—including GSK , AbbVie , Boehringer Ingelheim and Eli Lilly —to follow suit in pursuing therapies based on small interfering RNA (siRNA). And it’s not just the number of companies involved that’s expanding: while all siRNA therapies approved so far target the liver, Alnylam and others are now seeing some success in targeting other organs as well. The past two years have seen billions of dollars change hands in a bid to be part of this rapidly growing field. In January 2024, for example, Boehringer Ingelheim announced an agreement potentially worth more than $2 billion with Chinese biotech Suzhou Ribo Life Science and its Swedish unit Ribocure Pharmaceuticals to develop siRNA-based treatments for nonalcoholic or metabolic dysfunction-associated steatohepatitis (MASH), a disease expected to afflict 27 million Americans by 2030. And just last month, GSK plunked down $1.2 billion for Boston Pharmaceuticals’ investigational FGF21 analog efimosfermin alfa, also targeting MASH. “I think the siRNA space, for rare disease predominantly, has been revolutionary in a handful of cases,” said Myles Minter, a senior biotech analyst at William Blair. “And I do think that the large promise of the field to go into broader, more prevalent indications and to get more approvals is largely ahead of us.” A Genetic On/Off Switch The term RNA interference dates back to a 1998 paper by Craig Mello and colleagues, who found that double-stranded RNA was more effective than single strands in silencing genes with corresponding sequences in C. elegans . The mechanism turned out to also work in mammalian cells , and in 2002, multiple researchers who’d led key studies of the phenomenon, including Mello, teamed up with investors to found Alnylam. It took 16 years to gain FDA approval for the first siRNA drug, Onpattro, for polyneuropathy of hereditary transthyretin-mediated amyloidosis, a rare genetic disorder caused by mutations in the transthyretin ( TTR ) gene. One challenge Alnylam faced in the intervening years was in designing siRNAs that could escape degradation within the body for long enough to be effective, explained Vasant Jadhav, the company’s chief technology officer. But the biggest hurdle—one not unique to siRNAs—was getting the nucleic acid payloads where they needed to go. Then, in 2014, Alnylam researchers and their academic colleagues reported that linking siRNAs with a ligand called GalNAc would get them into cells in the liver, but not into other organs. Onpattro, approved in 2018, is a GalNac-linked siRNA. The drug “was pretty revolutionary at the time,” Minter said, because rather than simply treating symptoms or even slowing the toll of polyneuropathy of hereditary transthyretin-mediated amyloidosis, it elicited functional improvement. “The way I like to think about siRNA is that it’s a way that you can titrate, so you can dose at a genetic level. And it’s really one of the only modalities that you can do that with,” Minter told BioSpace . Other therapies followed from Alnylam for hypercholesterolemia (Leqvio, developed and commercialized by Novartis), acute hepatic porphyria (Givlaari) and primary hyperoxaluria type 1 (Oxlumo). Apart from Alnylam and its partners Sanofi and Novartis, the only other company to get an siRNA drug onto the market so far is Novo Nordisk, whose Rivfloza (nedosiran), approved by the FDA in 2023, treats the rare genetic disease primary hyperoxaluria type 1 (PH1). Testing the Limits So far, all of these therapies have targeted processes in the liver—including Amvuttra, which takes aim at cardiac outcomes via knocking down transthyretin (TTR) in hepatic cells. But experts who spoke with BioSpace said that could soon change. “Where we’re starting to see innovation—and it still is early stage, although it looks very promising—is trying to deliver to new tissues,” Minter said. That targeting problem is “the major question in the field that we’re working on right now.” Andrew Adams, Eli Lilly’s group vice president, molecule discovery and director of the Lilly Institute for Genetic Medicines, echoed this. GalNAc has thus far been a “unicorn” in the field in terms of its specific and safe delivery, and “we have a lot of work to do to open up si[RNA]beyond the hepatocyte, but . . . probably once we crack it is going to be similar to when Alnylam and others initially cracked GalNAc, and you’ll just sort of walk your way down the list of indications in the new tissue that you open up,” he told BioSpace . “I think probably the most interesting space for the field right now is in delivery to the brain and going after diseases of the brain,” he said, citing Alnylam’s candidate mivelsiran, currently in Phase II for cerebral amyloid angiopathy and Phase I for Alzheimer’s disease. Lilly, too, is pursuing neurodegenerative targets with siRNA, Adams added. Other tissues with promising early data include adipose and lung. In a March conference presentation, for example, Arrowhead Pharmaceuticals released mouse data on two siRNA candidates devised to reduce body fat while preserving lean muscle mass. One targets hepatic cells’ expression of a gene, INHBE , that is involved in metabolic processes, while the other silences expression of ALK7 , a gene needed for fat storage, in lipocytes. Early clinical studies on both candidates have begun. And last spring, Arrowhead announced interim results of a Phase I/II study of ARO-RAGE, an siRNA that targets lung tissue and silences the receptor for advanced glycation end-products, a mediator of type 2 inflammation. In study participants with asthma, two doses of the candidate reduced serum levels of the target protein by up to 88%, the company reported. siRNA’s limitations don’t end at targeting. It can’t be used to completely knock out expression of a gene, only knock it down, and it can’t by itself be used against multiple genetic targets, Jadhav noted. In addition, RNAi can only dial gene expression down, so it can’t be used to directly boost levels of a deficient protein. Researchers have found workarounds for this in some cases, though. Jadhav cited the example of Givlaari, which treats acute hepatic porphyria. “In this metabolic pathway, the heme biosynthesis, one of the enzymes is mutated, and because of that, you have toxic intermediates that build up,” he said. Since siRNA can’t replace the mutated enzyme, the therapy instead targets a different enzyme, GO, that’s upstream of the toxic intermediates, lowering their levels. siRNA’s successes could pave the way for a more permanent treatment option, Adams said. “Once you’ve generated enough evidence over a long enough period of time in enough patients that getting rid of this protein [via siRNA] has no negative consequences in an adult . . . Probably at that point you start to feel confident to permanently change something, but I think the bar should be and is high for things that people will tolerate permanent genetic changes for,” he said. He raised the example of Leqvio, which targets the enzyme PCSK9 in order to lower cholesterol levels. Verve Therapeutics now has a gene editor targeting the same enzyme in early clinical trials. Jadhav allowed that gene editing could become a competitor to siRNA in some cases. “I think at the end of the day, any solution . . . biopharma brings for the patients would be great,” he said. “At the same time, we feel that with RNAi, we can achieve [a] durable level of activity and still be reversible. You kind of get the best of both things. So we remain very confident and very optimistic about the future of RNAi.” Looking ahead, Minter summarized what he sees as the prospects for siRNA: “we’re at the precipice where we’re waiting, but it’s an exciting five to ten years ahead for the field, no doubt.”

上市批准临床2期临床结果临床1期

2025-06-05

·CPHI制药在线

收藏 | 现有管线与上市RNA疗法汇总

关注并星标CPHI制药在线RNA疗法正迅速成为现代医学中最具变革性的治疗策略之一。从反义寡核苷酸（ASO）和小干扰RNA（siRNA）等精准调控基因表达的工具，到mRNA疫苗和肿瘤免疫疗法等前沿应用，RNA技术已在多个疾病领域展现出巨大潜力。近年来，随着递送系统、生物偶联技术和修饰化学的不断进步，RNA疗法的临床管线迅速扩展，涵盖了罕见病、神经系统疾病、代谢性疾病以及肿瘤等多个领域。目前，RNA疗法的临床开发全景涵盖了ASO、siRNA、mRNA、核酸适体（aptamer）等主要技术路径，在不同适应症中布局广泛，关键企业的研发动态频繁，已获批上市的代表性药物不断涌现。本文总结了现有管线和上市的 RNA疗法，将这一新兴领域的开发全景呈现出来。1. ASO类 RNA资产梳理 1.1 I期ASO资产 • Praxis ASO资产：Elsunersen（PRAX-222）靶点：SCN2A基因适应症：由SCN2A基因的功能获得性突变引起的早发性SCN2A发育性和癫痫性脑病。 • PYC Therapeutics ASO资产：VP-001 靶点：PRPF31基因适应症：由PRPF31基因突变引起的视网膜色素变性11型 ASO资产：PYC-001 靶点：OPA1基因适应症：由OPA1基因突变引起的常染色体显性视神经萎缩（ADOA） ASO资产：PYC-003 靶点：PKD1基因适应症：常染色体显性多囊肾病（ADPKD） • Bio-Path Holdings ASO资产：BP1002（Liposomal Grb2 ASO）适应症：急性髓性白血病（AML）、B细胞淋巴瘤（B-cell lymphoma）技术特点：使用独特的中性脂质体递送系统（DNAbilize® Platform）递送ASO。1.2 II期ASO资产 • Stoke Therapeutics ASO资产：Zorevunersen（STK-001）靶点：SCN1A基因适应症：Dravet综合征（一种严重癫痫） ASO资产：STK-002 靶点：OPA1基因适应症：常染色体显性视神经萎缩（ADOA） • Entrada Therapeutics ASO资产：ENTR-601-44 适应症：Duchenne肌营养不良（DMD）靶点：DMD中的Exon 44跳跃技术特点：使用Entrada独有的分子穿透技术（Endosomal Escape Vehicle, EEV）提高细胞内递送效率。 ASO资产：ENTR-601-45 靶点：DMD基因的外显子45（Exon 45）适应症：适用于外显子45跳跃的杜氏肌营养不良症（DMD）患者 • Dyne Therapeutics ASO资产：DYNE-251 适应症：Duchenne肌营养不良（DMD），针对DMD中的Exon 51跳跃。技术特点：使用抗体-寡核苷酸结合平台（FORCE platform）进行肌肉组织特异性递送。 ASO资产：DYNE-101 适应症：肌强直性营养不良症1型（DM1）靶点：DMPK基因的异常CTG重复序列 • Ribomic ASO资产：Umedaptanib Pegol（原RBM-007，严格来说是核酸适体aptamer，而不是典型ASO) 靶点：FGF2（成纤维细胞生长因子2）。适应症：湿性年龄相关性黄斑变性（wAMD），软骨发育不全症 • Wave Life Sciences ASO资产： WVE-N531：DMD（杜氏肌营养不良症）治疗，靶向Exon 53跳跃 WVE-003：亨廷顿舞蹈症（Huntington's Disease, HD），靶向HTT基因突变 • PepGen ASO资产：PGN-EDO51 适应症：Duchenne肌营养不良（DMD）技术特点：结合增强型细胞穿透肽（Enhanced Delivery Oligonucleotide, EDO）技术，提高ASO进入肌肉细胞的效率。 ASO资产：PGN-EDODM1 靶点：DMPK基因的异常CUG重复序列适应症：肌强直性营养不良症1型（DM1） • 罗氏 ASO资产：Tominersen（RG6042）靶点：Huntingtin（HTT）基因适应症：亨廷顿病（Huntington's Disease, HD） ASO资产：IONIS-FB-LRx（RO7434656 / RG6299）靶点：补体因子B（Factor B）适应症：IgA肾病（IgAN） • Ultragenyx ASO资产：GTX-102 靶点：UBE3A-AS（UBE3A反义转录本）适应症：天使综合征（Angelman Syndrome）1.3 ASO类3期资产 • Oncotelic Therapeutics ASO资产：OT-101（也叫Trabedersen）靶点：转化生长因子β2（TGF-β2）适应症：胶质母细胞瘤（GBM）、胰腺癌、恶性黑色素瘤机制：抑制TGF-β2，有望减轻肿瘤免疫抑制，增强抗肿瘤免疫反应 • 阿斯利康 ASO资产：ION449（亦称AZD8233），与Ionis合作开发的ASO疗法靶点：PCSK9（一种影响低密度脂蛋白胆固醇LDL-C水平的蛋白质）适应症：高胆固醇血症（hypercholesterolemia）备注：主要竞争对手包括小分子抑制剂和PCSK9单抗（如Repatha、Praluent） • GSK ASO资产：bepirovirsen 靶点：乙型肝炎病毒（HBV）的前基因组RNA和mRNA 适应症：慢性乙型肝炎（chronic hepatitis B, CHB），通过抑制HBV基因表达，帮助病毒清除或实现功能性治愈（functional cure）。 • 诺华 ASO资产：Pelacarsen 靶点：LPA基因（编码脂蛋白(a)）作用机制：Pelacarsen通过抑制LPA基因的mRNA，降低血液中脂蛋白(a)(Lp(a))水平，从而降低心血管疾病风险。Lp(a)是目前被认为的重要但尚无针对性治疗手段的心血管风险因子。适应症：主要用于治疗动脉粥样硬化性心血管疾病高危患者中，血脂异常（特别是Lp(a)升高）的情况。临床阶段：正在进行III期临床试验（Lp(a)HORIZON）。Pelacarsen可能成为首个专门针对Lp(a)升高治疗获批的药物。1.4 ASO类上市药物 • 渤健 Spinraza（nusinersen）靶点：SMN2前体mRNA（促进功能性SMN蛋白表达）适应症：脊髓性肌萎缩症（SMA）获批时间：2016年12月（美国FDA批准）备注：全球首个获批的SMA治疗药物。由Ionis开发，Biogen负责商业化。 • Sarepta Therapeutics Exondys 51（eteplirsen）靶点：DMD基因的Exon 51 适应症：Duchenne肌营养不良（DMD）获批时间：2016年9月（FDA加速批准） Vyondys 53（golodirsen）靶点：DMD基因的Exon 53 适应症：DMD 获批时间：2019年12月 Amondys 45（casimersen）靶点：DMD基因的Exon 45 适应症：DMD 获批时间：2021年2月（FDA加速批准） • Ionis Pharmaceuticals Tegsedi（inotersen）靶点：TTR（转甲状腺素蛋白）适应症：遗传性转甲状腺素蛋白淀粉样变性多发性神经病（hATTR-PN）获批时间：2018年10月（FDA，EMA批准） Waylivra（volanesorsen）靶点：APOC3（载脂蛋白C-III）适应症：家族性乳糜微粒血症综合征（FCS）获批时间：2019年5月（欧洲EMA批准；未获美国FDA批准） • NS Pharma Viltepso（viltolarsen）靶点：DMD基因的Exon 53 适应症：Duchenne肌营养不良（DMD）获批时间：2020年8月（FDA加速批准）2.RNAi类 RNA资产2.1 I期RNAi资产 • Aligos Therapeutics RNAi资产：ALG-125755 靶点：乙型肝炎病毒（HBV）RNA 适应症：慢性乙型肝炎（CHB） • Regulus Therapeutics RNAi资产：RGLS8429 靶点：microRNA-17（miR-17家族）适应症：常染色体显性多囊肾病（ADPKD） • Phio Pharmaceuticals RNAi资产：PH-762 靶点：程序性死亡受体1（PD-1）适应症：癌症免疫疗法（通过下调T细胞表面PD-1，增强免疫杀伤）技术特点：采用其自有的INTASYL✓平台，优化了siRNA的稳定性和局部递送。 • TransCode Therapeutics RNAi资产：VIR-2218 TTX-MC138 靶点：microRNA-10b（miR-10b）适应症：针对转移性实体肿瘤（如乳腺癌、胰腺癌、脑肿瘤等）技术特点：使用纳米颗粒系统高效递送siRNA药物，特别适合针对深部转移灶。2.2 II期RNAi资产 • Arbutus Biopharma RNAi资产：AB-729 靶点：乙型肝炎病毒（HBV）表面抗原（HBsAg）适应症：慢性乙型肝炎（CHB）备注：AB-729是Arbutus当前最重要的核心资产之一。 • OliX Pharmaceuticals RNAi资产：OLX703A 靶点：HBV病毒相关RNA 适应症：慢性乙型肝炎（CHB）机制：抑制HBV病毒蛋白表达 • Silence Therapeutics RNAi资产：SLN360 靶点：LPA基因（编码脂蛋白Lp(a)）适应症：高脂蛋白(a)血症（Lp(a)过高相关的心血管疾病）机制：通过降低血液中Lp(a)水平，减少动脉粥样硬化风险。备注：SLN360是Silence在心血管RNA疗法领域的主力项目。 • Sirnaomics RNAi资产：STP705 靶点：双靶点siRNA药物，靶向TGF-β1和COX-2。适应症：瘢痕治疗（皮肤纤维化）、非黑色素瘤皮肤癌（如基底细胞癌、鳞状细胞癌）机制：抑制纤维化、降低肿瘤微环境免疫抑制。备注：Sirnaomics的特点是双靶点siRNA联合递送。 • GSK RNAi资产：GSK4532990 靶点：靶向HSD17B13基因适应症：代谢功能障碍相关脂肪性肝炎（MASH） • 礼来 RNAi项目：LY3561774 靶点：SERPINA1基因适应症：α1-抗胰蛋白酶缺乏症（AATD）机制：降低异常α1-抗胰蛋白酶（AAT）积聚 • VIR Biotechnology RNAi项目：VIR-2218 靶点： HBV RNA 适应症：慢性乙型肝炎（CHB）。机制：抑制HBV表面抗原表达 • 罗氏 RNAi资产：Zilebesiran 靶点：肝脏表达的血管紧张素原（AGT）基因。适应症：高血压，特别是高心血管风险患者。2.3 III期RNAi资产 • Arrowhead Pharmaceuticals RNAi资产：ARO-APOC3 靶点：APOC3（载脂蛋白C-III），适应症：高甘油三酯血症和罕见脂代谢异常 • 武田 RNAi资产：Fazirsiran 靶点：SERPINA1（编码α1-抗胰蛋白酶）适应症：α1-抗胰蛋白酶缺乏症（AATD）引起的肝病 • 安进 RNAi资产：Olpasiran 靶点：LPA基因（脂蛋白(a)）适应症：高脂蛋白(a)血症及其引发的心血管疾病风险备注：这是一款非常重磅的RNAi项目，对心血管领域意义重大。 • Avidity Biosciences RNAi资产：AOC 1001 靶点：DMPK基因（导致肌强直性营养不良症1型DM1）适应症：肌强直性营养不良症1型（DM1）技术特点：AOC（Antibody Oligonucleotide Conjugate，抗体-寡核苷酸偶联体），用于肌肉靶向递送siRNA。 • 赛诺菲 RNAi资产：Fitusiran 靶点：AT（抗凝血酶）适应症：血友病A或B患者的出血预防 • VIR Biotechnology RNAi资产：VIR-2218 靶点：HBV RNA 适应症：慢性乙型肝炎（CHB）2.4 上市RNAi资产 • Alnylam Pharmaceuticals Alnylam是全球RNAi疗法先锋，拥有最多已上市RNAi药物。 Onpattro（Patisiran）靶点：TTR 适应症：遗传性转甲状腺素蛋白淀粉样变性引起的多发性神经病（hATTR-PN）批准情况：2018年FDA/EMA批准 Givlaari（Givosiran）靶点：ALAS1 适应症：急性肝卟啉症（AHP）批准情况：2019年FDA/EMA批准 Oxlumo（Lumasiran）靶点：HAO1 适应症：原发性高草酸尿症1型（PH1）批准情况：2020年FDA/EMA批准 Amvuttra（Vutrisiran）靶点：TTR 适应症：遗传性转甲状腺素蛋白淀粉样变性引起的多发性神经病（hATTR-PN）（长效皮下注射版）批准情况：2022年FDA批准 • 诺华 RNAi资产：Leqvio（Inclisiran）靶点：PCSK9 适应症：高胆固醇血症，动脉粥样硬化性心血管疾病风险降低批准情况：2020年欧洲EMA批准；2021年底美国FDA批准 • 诺和诺德 RNAi资产：Rivfloza (nedosiran) 靶点：肝脏中乳酸脱氢酶（LDH）mRNA 适应症：治疗9岁及以上、肾功能相对良好的原发性高草酸尿症1型（PH1）患者。作用机制：抑制LDH蛋白表达，减少草酸过度生成，缓解PH1疾病过程，减少肾脏损害风险。批准情况：2023年9月29日FDA正式批准Rivfloza上市。成为继Alnylam的Oxlumo（Lumasiran）之后，全球第二款获批用于PH1治疗的RNAi药物。3.mRNA类 RNA药物资产3.1 1期mRNA资产 • 赛诺菲 SP0237: 季节性流感 mRNA 疫苗适应症：针对 A/H3N2 毒株的季节性流感。 SP0256 – RSV mRNA 疫苗（老年人群）适应症：用于预防老年人群中的呼吸道合胞病毒（RSV）感染。 SP0268 – mRNA 痤疮疫苗适应症：针对痤疮（Acne）的 mRNA 疫苗。 SP0291 – 多价呼吸道病毒 mRNA 疫苗适应症：针对 RSV、人类偏肺病毒（hMPV）和副流感病毒 3 型（PIV3）的组合疫苗，主要用于老年人群。沙眼衣原体（Chlamydia）mRNA 疫苗候选适应症：预防沙眼衣原体感染，主要针对 18 至 29 岁的成人。 • Vertex mRNA资产：VX-522：用于囊性纤维化（CF）的mRNA疗法靶点：CFTR基因（囊性纤维化跨膜电导调节因子）。适应症：无法通过CFTR调节剂治疗的CF（囊性纤维化）患者，尤其是那些由于CFTR基因突变导致CFTR蛋白缺失的患者。作用机制：VX-522是一种mRNA疗法，通过脂质纳米颗粒（LNP）递送CFTR mRNA至肺部细胞，促使其合成功能性CFTR蛋白，从而恢复氯离子通道的功能。3.2 II期mRNA资产 • Gritstone Bio GRANITE（GRT-C901/GRT-R902）个体化肿瘤新抗原疫苗，采用腺病毒（ChAd68）和自扩增mRNA（samRNA）组成的异源prime-boost策略。适应症：用于治疗转移性微卫星稳定型结直肠癌（MSS-CRC）。 CORAL 基于自扩增mRNA（samRNA）的COVID-19疫苗，诱导广泛且持久的中和抗体和T细胞免疫反应。 • CureVac/GSK 季节性流感mRNA疫苗候选该疫苗候选基于CureVac的第二代mRNA平台，针对流感病毒株，包括A型和B型毒株。 COVID-19 mRNA疫苗候选CV0601和CV0701 CV0601为单价疫苗，编码Omicron BA.4/5变异株的刺突蛋白；CV0701为二价疫苗，编码Omicron BA.4/5变异株和原始SARS-CoV-2毒株的刺突蛋白。3.3 III期mRNA资产 • 第一三共 DS-5670a（原始毒株单价疫苗）适应症：Covid-19疫苗，作为加强针用于已完成初始疫苗接种的成人和老年人。 DS-5670a/b（原始毒株与Omicron BA.4/5二价疫苗）适应症：Covid-19疫苗，作为加强针用于12岁及以上已完成初始疫苗接种的人群。 DS-5670d（Omicron XBB.1.5单价疫苗）适应症：Covid-19疫苗，作为季节性加强针用于12岁及以上人群，包括未接种疫苗者。 • 默沙东 mRNA资产：V940（mRNA-4157）类型：肿瘤疫苗（个体化mRNA疫苗）适应症：手术切除后的高风险黑色素瘤患者辅助治疗靶点：个体化新抗原（根据患者肿瘤突变特异设计）3.4上市mRNA资产 • Arcturus Therapeutics mRNA资产：KOSTAIVE（ARCT-154 / Zapomeran）类型：自扩增mRNA（sa-mRNA）疫苗适应症：用于预防COVID-19，适用于18岁及以上人群靶点：SARS-CoV-2病毒刺突蛋白（Spike protein） • BioNTech/辉瑞 Comirnaty 类型：mRNA疫苗适应症：用于预防COVID-19，适用于6个月及以上人群靶点：SARS-CoV-2病毒刺突蛋白（Spike protein）获批时间：✓2020年12月获得FDA紧急使用授权，2021年8月获得美国FDA完全批准 • 莫德纳 Spikevax 类型：mRNA疫苗适应症：用于预防COVID-19，适用于6个月及以上人群靶点：SARS-CoV-2病毒刺突蛋白（Spike protein）获批时间：2020年12月18日，美国FDA授予紧急使用授权；2022年1月31日，获得FDA完全批准Ref. TD Cowen. Pharmaceuticals’ websitesEND【企业推荐】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~

临床2期寡核苷酸上市批准信使RNA临床1期

100 项与芬妥司兰钠相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15002

研发状态

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适应症	国家/地区	公司	日期
血友病A	美国	Genzyme Corp.	2025-03-28
血友病B	美国	Genzyme Corp.	2025-03-28

未上市

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适应症	最高研发状态	国家/地区	公司	日期
出血	临床3期	美国	Sanofi	2023-02-01
出血	临床3期	中国	Sanofi	2023-02-01
出血	临床3期	日本	Sanofi	2023-02-01
出血	临床3期	加拿大	Sanofi	2023-02-01
出血	临床3期	法国	Sanofi	2023-02-01
出血	临床3期	德国	Sanofi	2023-02-01
出血	临床3期	希腊	Sanofi	2023-02-01
出血	临床3期	匈牙利	赛诺菲（中国）投资有限公司	2023-02-01
出血	临床3期	匈牙利	Sanofi-Aventis Recherche & Développement SA	2023-02-01
出血	临床3期	印度	Sanofi	2023-02-01

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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


NCT03417102 \| NCT03417245 \| NCT03754790 (ATLAS-OLE, FDA_CDER) 人工标引	临床3期	血友病B \| 血友病A	-	QFITLIA AT-DR (prior bypassing agent)	糧觸餘鹹遞願糧願餘獵(壓鬱糧糧築蓋範觸鹽糧) = 艱遞艱構淵衊網齋餘鬱窪淵積願鹽憲觸簾構艱 (艱構觸醖膚願願製鏇鬱, 2.8 ~ 9.5) 更多	积极	2025-03-28
				On-Demand BPA (prior bypassing agent)	糧觸餘鹹遞願糧願餘獵(壓鬱糧糧築蓋範觸鹽糧) = 壓範鏇糧鬱夢構願糧範窪淵積願鹽憲觸簾構艱 (艱構觸醖膚願願製鏇鬱, 11.8 ~ 31.0) 更多
NCT02554773 (Pubmed) 人工标引	临床2期	血友病B \| 血友病A	34	fitusiran (AT-based dose regimen)	淵淵網選鏇衊積築築製(鑰選衊製齋獵範選製選) = 壓鹽鑰衊窪築夢範顧窪艱獵糧觸窪餘觸願襯簾 (繭繭餘憲簾獵衊蓋廠憲 )	积极	2024-12-06
				fitusiran (the original dose regimen)	淵淵網選鏇衊積築築製(鑰選衊製齋獵範選製選) = 獵蓋鹹糧艱壓餘鏇遞廠艱獵糧觸窪餘觸願襯簾 (繭繭餘憲簾獵衊蓋廠憲 )
EHA2024	N/A	-	25	octocog alfa	膚繭蓋鹽齋憲夢鏇簾窪(積衊夢憲範觸壓構襯顧) = 積艱窪範網積顧鬱壓築壓繭夢鬱積餘鹹夢蓋鑰 (觸製艱蓋繭衊網製觸鏇, 38)	-	2024-05-14
				emicizumab	膚繭蓋鹽齋憲夢鏇簾窪(積衊夢憲範觸壓構襯顧) = 選淵鏇鬱觸艱築鑰壓製壓繭夢鬱積餘鹹夢蓋鑰 (觸製艱蓋繭衊網製觸鏇, 9)
NCT03417102 (ATLAS-INH, Pubmed) 人工标引	临床3期	血友病B \| 血友病A	57	fitusiran	壓膚網繭壓觸簾糧艱選(蓋顧築淵繭構築艱構鬱) = 遞選築齋廠繭鹹鹽顧製齋餘顧繭餘選齋窪夢觸 (衊蓋顧餘糧鏇膚鏇選鏇, 1.0 ~ 2.7) 更多	积极	2023-04-29
				bypassing agents	壓膚網繭壓觸簾糧艱選(蓋顧築淵繭構築艱構鬱) = 鏇窪遞願膚糧憲糧獵蓋齋餘顧繭餘選齋窪夢觸 (衊蓋顧餘糧鏇膚鏇選鏇, 10.6 ~ 30.8) 更多
NCT03549871 (ATLAS-PPX, GlobeNewswire) 人工标引	临床3期	出血 \| 血友病B	80	Fitusiran	蓋蓋餘夢壓積窪艱鹹廠(醖範夢範繭構網構蓋鏇) = 膚廠鹹遞襯襯鑰壓鑰窪繭築顧淵醖範簾構遞淵 (鏇製廠觸獵願鬱選鹽憲 ) 更多	积极	2022-07-10
NCT03549871 (ATLAS-PPX, ISTH2022)	临床3期	血友病	217	fitusiran	憲簾襯餘選鑰糧衊廠淵(願鑰選膚範願鬱餘憲窪) = 鹹鬱鹽簾淵淵窪獵醖鬱製餘窪夢襯餘鑰鹹鹽範 (衊獵鬱窪淵膚選夢選憲 )	-	2022-07-09
NCT03417245 \| NCT03417102 (ATLAS-INH, ISTH2022)	临床3期	血友病 inhibitors	118	Fitusiran prophylaxis	網蓋夢範鏇齋簾壓淵醖(範網壓膚糧製夢製糧糧) = 餘夢築淵夢齋遞遞壓願餘製廠積餘鑰淵廠繭繭 (繭廠鬱積觸願遞廠積襯 ) 更多	-	2022-07-09
NCT03417102 (ISTH2022)	临床3期	血友病A	-	Fitusiran prophylaxis	窪選積糧淵獵夢餘壓鏇(夢壓糧鹹構廠鑰蓋夢繭) = 襯窪積鑰選範夢膚膚醖蓋繭製簾艱窪網餘醖齋 (網壓憲蓋窪鬱鹽顧鹽夢 ) 更多	-	2022-07-09
NCT03417245 (ATLAS-A/B, ASH2021) 人工标引	临床3期	血友病B \| 血友病A	116	once-monthly 80 mg SC fitusiran prophylaxis	衊願憲夢憲獵膚觸構憲(衊鬱艱範鑰窪艱壓餘選) = 鬱觸顧壓願繭鑰範獵顧範獵願簾遞蓋顧衊顧廠 (構衊廠蓋製鏇構願遞鏇, 84.1 ~ 93.6) 更多	积极	2021-12-04
				on-demand (OD) treatment with factor concentrates	衊願憲夢憲獵膚觸構憲(鬱糧積鑰選繭鹹構遞觸) = 範觸構膚鏇遞憲範蓋遞製選構鬱製選膚鏇襯鏇 (衊鹹構遞餘築衊遞網窪, 8.4 ~ 41.0) 更多