To evaluate the efficacy and safety of patisiran in patients with wtATTR amyloidosis and symptomatic polyneuropathy by evaluating the effect on neurologic impairment and quality of life.

开始日期2022-08-03

申办/合作机构

Alnylam Pharmaceuticals, Inc.

NCT04201418 / CompletedN/A

A Phase 4 Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of Hereditary Transthyretin-Mediated (ATTRv) Amyloidosis With a V122I or T60A Mutation

To evaluate the effectiveness of patisiran in patients with ATTRv amyloidosis with polyneuropathy who have a V122I or T60A mutation.

开始日期2019-12-18

申办/合作机构

Alnylam Pharmaceuticals, Inc.

NCT03997383 / Active, not recruiting临床3期

APOLLO-B: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Patisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

The purpose of this study is to evaluate the efficacy and safety of patisiran in participants with ATTR amyloidosis with cardiomyopathy.

开始日期2019-09-04

申办/合作机构

Alnylam Pharmaceuticals, Inc.

100 项与 Patisiran sodium 相关的临床结果

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100 项与 Patisiran sodium 相关的转化医学

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100 项与 Patisiran sodium 相关的专利（医药）

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209

项与 Patisiran sodium 相关的文献（医药）

2024-01-02·Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

Reduction in ^99m Tc-DPD myocardial uptake with therapy of ATTR cardiomyopathy

Article

作者: Loewe, Christian ; Auer-Grumbach, Michaela ; Willixhofer, Robin ; Kastner, Johannes ; Badr Eslam, Roza ; Calabretta, Raffaella ; Donà, Carolina ; Hengstenberg, Christian ; Kammerlander, Andreas ; Bonderman, Diana ; Nitsche, Christian ; Kastl, Stefan ; Poledniczek, Michael ; Duca, Franz ; Beitzke, Dietrich ; Hacker, Marcus ; Rettl, René ; Bergler-Klein, Jutta ; Binder, Christina ; Kronberger, Christina

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.Methods and results: ATTRv-CM patients underwent [^99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function.Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial ^99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.

2024-01-02·Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

Treatment response and neurofilament light chain levels with long-term patisiran in hereditary transthyretin-mediated amyloidosis with polyneuropathy: 24-month results of an open-label extension study

Article

作者: Polydefkis, Michael ; Ueda, Mitsuharu ; Aldinc, Emre ; Coelho, Teresa ; Hale, Cecilia ; Ticau, Simina ; Vest, John ; Adams, David ; Nioi, Paul

BACKGROUND:

Longitudinal changes in neurofilament light chain (NfL) levels were evaluated alongside prespecified clinical assessments 24 months into the patisiran Global open-label extension (OLE) study in patients with ATTRv amyloidosis with polyneuropathy.

METHODS:

All patients enrolled in the Global OLE, from phase III APOLLO and phase II OLE parent studies, received patisiran. Assessments included measures of polyneuropathy (modified Neuropathy Impairment Score+7 (mNIS+7)), quality of life (QOL; Norfolk QOL-Diabetic Neuropathy questionnaire (Norfolk QOL-DN)), and plasma NfL.

RESULTS:

Patients receiving patisiran in the parent study (APOLLO-patisiran, n = 137; phase II OLE-patisiran, n = 25) demonstrated sustained improvements in mNIS+7 (mean change from parent study baseline (95% confidence interval): APOLLO-patisiran -4.8 (-8.9, -0.6); phase II OLE-patisiran -5.8 (-10.5, -1.2)) and Norfolk QOL-DN (APOLLO-patisiran -2.4 (-7.2, 2.3)), and maintained reduced NfL levels at Global OLE 24 months. After initiating patisiran in the Global OLE, APOLLO-placebo patients (n = 49) demonstrated stabilized mNIS+7, improved Norfolk QOL-DN, and significantly reduced NfL levels. Patisiran continued to demonstrate an acceptable safety profile. Earlier patisiran initiation was associated with a lower exposure-adjusted mortality rate.

CONCLUSIONS:

Long-term patisiran treatment led to sustained improvements in neuropathy and QOL, with NfL demonstrating potential as a biomarker for disease progression and treatment response in ATTRv amyloidosis with polyneuropathy.

2024-03-01·Advanced drug delivery reviews

mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond

Review

作者: García Del Valle, Lucía ; Estapé Senti, Mariona ; Schiffelers, Raymond M

mRNA-based vaccines are emerging as a promising alternative to standard cancer treatments and the conventional vaccines. Moreover, the FDA-approval of three nucleic acid based therapeutics (Onpattro, BNT162b2 and mRNA-1273) has further increased the interest and trust on this type of therapeutics. In order to achieve a significant therapeutic efficacy, the mRNA needs from a drug delivery system. In the last years, several delivery platforms have been explored, being the lipid nanoparticles (LNPs) the most well characterized and studied. A better understanding on how mRNA-based therapeutics operate (both the mRNA itself and the drug delivery system) will help to further improve their efficacy and safety. In this review, we will provide an overview of what mRNA cancer vaccines are and their mode of action and we will highlight the advantages and challenges of the different delivery platforms that are under investigation.

458

项与 Patisiran sodium 相关的新闻（医药）

2024-08-30

·FiercePharma

Alnylam's Amvuttra turns in 'grand slam' showing in ATTR-CM, but leaves a window open for rivals

After releasing pivotal trial data for Amvuttra in transthyretin amyloid cardiomyopy (ATTR-CM), Alnylam is ready to pursue a label expansion and play ball with Pfizer in a market showdown. Alnylam is circling the bases after walloping—in the words of chief medical officer Pushkal Garg M.D.—a “grand slam” with data that position its RNA silencer Amvuttra (vutrisiran) to potentially become a standard-of-care treatment for the rare heart disease transthyretin amyloid cardiomyopathy (ATTR-CM).Alnylam on Friday provided detailed results from the phase 3 HELIOS-B study, which met all 10 of its primary and secondary endpoints in both its overall and monotherapy populations, bolstering the company's claim that Amvuttra will challenge Pfizer’s Vyndaqel (tafamidis) franchise. Alnylam shared the results at the European Society of Cardiology conference in London.While Alnylam hailed the results, some analysts and investors took issue with the study findings. Mid-morning Friday, the company's shares were down about 7% as the results apparently failed to live up to expectations."Objectively this data appears to be short of the aforementioned investor bar," wrote Myles Minter, Ph.D., an analyst with William Blair.In June, Alnylam made waves when it released top-line data from the trial. On Friday, the company filled in the blanks with mortality and cardiovascular hospitalization endpoint curves, additional data on subgroups, as well as complete results from a 6-minute walk test. Also presented were findings from the patient-reported Kansas City Cardiomyopathy Questionnaire (KCCQ), plus the New York Heart Association (NYHA) heart failure classification survey.In the overall study group of 654 patients, including those who were on Pfizer's tafamadis, Amvuttra reduced the risk of death or recurrent cardiovascular events by 28% versus placebo. Of those in the monotherapy group—which comprised 60% of the patients in the trial—Amvuttra reduced the risk of death or recurrent cardiovascular events by 33% compared to placebo.In one crucial dataset that analysts have been waiting for, Amvuttra reduced the risk of death or recurrent cardiovascular events by 22% in patients who were taking tafamidis at the start of the study. The siRNA therapy also led to a 41% reduction in all-cause mortality among tafamadis takers through 42 months versus placebo."It suggests that, while not head-to-head, that you're seeing very compelling efficacy from this agent," Garg said in an interview earlier this week."With the level of benefit, we think vutrisiran is well positioned both as monotherapy as well as add on to tafamidis, boding well for market uptake after generic tafamidis entry in 2028," analysts at Evercore ISI wrote in a note to clients.Amvuttra started to show a survival benefit—as the all-cause mortality curves separated—in the overall study population at 18 months, which was in line with Pfizer's ATTR-ACT trial for tafamidis. For the group of patients in HELIOS-B who were using tafamidis at baseline, the curves separated at 24 months.The study was statistically powered to measure Amvuttra as a monotherapy and in the overall trial population, but not specifically on the subgroup of patients who received both tafamidis and the Alnylam drug. Later this year, Alnylam is kicking off a phase 3 study designed to show the value of Amvuttra and tafamidis as a combination treatment.Still, the company believes that the results are overwhelming evidence that Amvuttra is transformative in the indication.“We think this represents the potential for this drug to become the new standard of care for this disease, something that can be used front line in patients but also in those who are not optimally managed with current medicines as a switch therapy or even as an add-on over time,” Garg added.Subgroup analyses also showed all-cause mortality reductions of up to 65% in newly diagnosed patients.“We see disproportionate benefits in patients with earlier disease—those who are younger or have (less severe forms of the disease)—which really highlights the importance of getting the most effective treatment as early as possible,” Garg added. In an additional endpoint, which was revealed in June, in the overall patient population there was a 36% reduction in the risk of death up to month 42, while in the Amvuttra monotherapy group, there was a 35% reduction in the risk of death over the same period.In addition to the 40% of patients on tafamidis at the baseline of HELIOS-B, 22% more of the participants began taking Pfizer’s drug during the course of the trial. On top of that, 30% of the patients were on an SGLT2 inhibitor.“This was a pretty heady gauntlet for this drug to have to show a benefit on top of,” Garg said. “It really showed a remarkable benefit across the full spectrum of patients on some very, very hard endpoints.”Alnylam plans to file for FDA approval of Amvuttra in ATTR-CM later this year and will use a priority review voucher, which will slice by four months the regulator’s standard 10-month appraisal period.Amvuttra was approved in June of 2022 for ATTR-polyneuropathy, a condition which has roughly one-tenth the population size of ATTR-CM. Amvuttra generated sales of $558 million in 2023.Meanwhile, Pfizer’s group of tafamidis drugs—which include Vydaqel, Vyndamax and Vynmac (outside the U.S.)—rang up (PDF) sales of $3.3 billion in 2023, which were up 36% in their fourth full year on the market.As an RNA interference drug, Amvuttra may have a mechanism of action edge on tafamidis. While it reduces the circulating levels of the transthyretin (TTR) protein and hence the amyloid clumps in the heart, tafamidis works by stabilizing the TTR. Alnylam contends that Amvuttra’s treatment effects may expand over time."What we do is work upstream transthyretin and turn off production in the liver," Garg said. "We're stopping the disease-causing protein from being formed in the first place." Still, challenging Pfizer’s entrenched, first-of-its-kind treatment will not be easy, according to a note two months ago from analysts at Leerink Partners, who cited the “ease of use, pristine safety and accumulated real-world data,” of tafamidis.As for the ease of use, while vutrisiran is administered once every three months by way of injection, tafamidis is a daily pill.Among other companies pursuing the emerging class of RNA interference drugs, Intellia and Ionis have what analysts viewed as one of the most promising investigative treatments. Alnylam’s first RNA silencer, Onpattro (patirisan), was approved for ATTR-polyneuropathy in 2018 but the FDA rejected it last year for ATTR-CM, overruling an advisory panel that recommended it for approval by a 9-3 vote.While tafamidis remains the only drug on the market for ATTR-CM, competition is likely on its way in the indication from BridgeBio as the FDA is reviewing its application for TTR stabilizer acoramidis. Friday, analysts at ISI Evercore said that while the data on Amvuttra were "obviously positive," the idea that the drug "would emerge the undisputed best-in-class therapy appears to be fading." Likewise, Mizuho's Salim Syed wrote in a note he'd seen "nothing suggestive that vutrisiran is better" than acoramidis. BridgeBio's shares jumped 10% in the wake of Alnylam's data release.

临床结果上市批准临床3期AHA会议优先审批

2024-08-28

·Business Wire

Alnylam to Webcast Presentations at Upcoming September Investor Conferences

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that management will present company overviews at the following conferences: Wells Fargo 2024 Healthcare Conference on Wednesday, September 4, 2024 at 9:30 am ET in Boston Morgan Stanley 22 nd Annual Global Healthcare Conference on Wednesday, September 4, 2024 at 1:05 pm ET in New York City A live audio webcast of each presentation will be available on the Investors section of the Company’s website at www.alnylam.com/events . A replay will be available on the Alnylam website within 48 hours after each event. About Alnylam Pharmaceuticals Alnylam Pharmaceuticals (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO ® (patisiran), AMVUTTRA ® (vutrisiran), GIVLAARI ® (givosiran), OXLUMO ® (lumasiran), and Leqvio ® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “ Alnylam P 5 x25 ” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam , or on LinkedIn , Facebook , or Instagram .

siRNA

2024-08-19

·药融圈

国内小核酸企业管线数量TOP15

▲8月15-16日 NDC2024生物医药创新者峰会扫码立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。随着2018年FDA批准siRNA药物Patisiran上市，小核酸药物迎来了发展的新纪元，越来越多的企业争相进入这一赛道。小核酸药物指长度小于30nt的寡核苷酸序列，可通过与靶分子的RNA结合，通过调控翻译，从而达到治疗疾病的效果。广义的小核酸包括小干扰RNA（siRNA）、反义寡核苷酸（ASO）、微小RNA（miRNA）、核酸适配体（Aptamer）等。小核酸药物具有高度的靶向性和特异性，可以精准地调控基因表达，因此在基因治疗和基因编辑等领域具有广阔的应用前景。小核酸药物也是今年以来国产创新药出海过程中含金量最高的赛道之一。2024年初，国投招商投资企业瑞博生物和舶望制药分别与勃林格殷格翰（Boehringer Ingelheim）及诺华（Novartis）达成海外授权合作，合计交易金额超60亿美元，这验证了其管线具有创新性与较高的临床价值。小核酸也成为了继ADC、单抗等领域之后，又一得到全球市场认可的细分新药研发领域。本文将对国内布局小核酸药物的企业进行盘点，并对部分企业管线进行梳理，以供参考。核酸药物行业发展现状核酸药物是一种在基因转录后、蛋白质翻译前阶段进行调控的疗法，作用于蛋白质合成上游，主要可分为小核酸药物和mRNA两大类。与传统的小分子药物和抗体药物相比，核酸药物具有设计简便、研发周期短、靶向特异性强、治疗领域广泛和长效性等优点，目前在遗传疾病、肿瘤、病毒感染等疾病的治疗上应用广泛，有望成为继小分子药物和抗体药物后的第三大类药物。截至目前，已有22款核酸药物获批上市，其中有16款小核酸药物，包括10款反义寡核苷酸（ASO）药物、5款siRNA药物和1款核酸适配体。弗若斯特沙利文公司分析指出，全球小核酸药物进入临床管线的共有近195个，其中约有11%进入了Ⅲ期临床，大多数集中在Ⅰ期和Ⅱ期临床。在药物类型上， ASO和 siRNA是当前临床研发数量最多的小核酸药物。其中ASO仍是当前研发热点，占比38%；siRNA发展快速，占比已达到32%，其余小核酸药物研发相对还处在早期阶段，整体数量较少。在适应证分布上，肿瘤和遗传病是临床管线中占比最多的，其中遗传病大多为一些罕见病，如遗传性血管性水肿、亨廷顿病、先天性厚甲症等。目前，我国有30余款小核酸药物研发进入临床研究阶段，大多数处于临床早期。虽然国内的小核酸药物行业仍然处于发展初期阶段，但由于国内患者群体基数较大、市场发展空间大，未来随着我国小核酸药物开发企业的研发能力提升，有望逐步进入差异化创新和突破性创新阶段，我国小核酸药物市场有望迎来快速发展。国内布局小核酸企业 RNAi 技术已成为生物制药公司的兵家必争之地，制药巨头与小核酸研发企业共谋发展，国外Ionis、Alnylam 引领发展；国内目前致力于小核酸药物的研发企业约有40家（如有遗漏，欢迎留言补充），通过自主研发和合作引进，迅速成长，苏州瑞博、圣诺医药处于领先水平。2023年舒泰神终止旗下乙肝RNAi药物STSG-0002注射液临床试验及后续开发，退出小核酸赛道。 1、舶望制药舶望制药成立于2021年4月，该公司致力于开发新一代siRNA药物，为全球患者提供急需的、更好的治疗手段。舶望制药团队在核酸序列设计、化学修饰、GalNAc递送技术、肝脏外组织靶向递送技术、寡聚核酸合成、CMC等RNAi药物开发的全流程环节拥有多年专业经验，已经在舶望制药建立起完整的核酸药物开发平台。公司目前的研发管线包含20多个治疗项目，已有5条管线处于临床阶段，多条管线确定PCC，适应症领域涵盖心血管疾病、罕见病、病毒感染、神经系统疾病等，已在中国、美国、澳洲等多地获得临床批件。其中，心血管领域的BW-01、BW-02已经进入临床阶段，应为此次授权的核心产品。根据申报信息，这两款心血管产品分别用于治疗血脂异常和高血压。 2024年5月，舶望制药宣布其心血管siRNA新药BW-01针对重度高甘油三酯血症的2期临床试验已于2024年4月29日完成首例受试者给药。同月，据CDE官网公示，舶望制药子公司杭州舶临医药科技有限公司申报的siRNA 1类新药BW-20507注射液获CDE临床试验默示许可，拟开发用于治疗慢性乙型肝炎。 2024年1月，舶望制药宣布与诺华就RNAi疗法达成两项独家许可合作协议。Argo将从诺华获得1.85亿美元的首付款，并有资格获得潜在的期权和里程碑付款，以及商业销售的分级版税。两项交易潜在总价值高达41.65亿美元。研发管线 2、瑞博生物瑞博生物成立于2007 年，是一家致力于开发RNAi技术的创新型药物研发企业，是中国RNAi技术和RNAi 制药的主要开拓者。 1）公司拥有完善系统的小核酸药物研发平台，覆盖核酸制药全产业链；2）siRNA递送系统技术领先；3）siRNA 液相合成技术实现技术突破，相较于现有的固相合成技术，大大提高了产能；4）公司国际合作经验丰富，2012 年与QUARK 结为战略合作伙伴，共同推进以RNAi药物为主的临床研究。2017年与Ionis达成合作，获得了Ionis三个分别用于治疗代谢疾病和癌症的药物品种在中国的全部研发和商业化权利。2024年瑞博生物与勃林格殷格翰合作共同开发治疗肝病的小核酸创新疗法；5）同时也取得了资本的有力支持，截至目前公司共获得融资13.58亿元。公司产品管线丰富，包括非动脉炎性前部缺血性视神经病变、糖尿病、前列腺癌、青光眼等适应症的siRNA药物，共有8个产品进入临床试验阶段，其中进度最快的是治疗 NAION(非动脉炎性前部缺血性视神经病变)的RBD1007，于2015年12月获批国际多中心II/III期关键性临床试验，也是国内首个获批国际多中心临床试验的小核酸药物。目前全球已经完成1个临床I期研究和1个Ⅱ/Ⅲ期国际多中心临床研究（其中包括34例中国受试者），临床试验数据分析结果支持针对具有极大未满足临床需求的NAION亚组患者人群开展III期确证性临床研究。此外RBD4988、RBD4059、RBD1016也相继进入了II期临床阶段。研发管线 3、圣诺医药圣诺医药成立于2007年，由一批来自美国顶尖制药公司的优秀科学家和企业家组成。2021年，圣诺医药登陆港交所，成为“国内小核酸药物第一股”。圣诺医药已开发出4个新型递送平台，包括多肽纳米颗粒（PNP）递送平台、新型 GalNac 递送平台和多肽-脂质纳米颗粒（PLNP）递送平台等，利用其特色平台进行小核酸药物研发。该公司研发管线丰富，适应症涵盖肿瘤、纤维化疾病、医学美容、代谢疾病和传染病等，已有治疗实体肿瘤的siRNA药物管线进入临床中后期研发阶段。圣诺医药正推进优先产品管线及在美国就主要临床候选药物STP705及STP707连同STP122G开展五项siRNA临床试验，这两种药物均通过双靶点（TGF-β1和COX-2）小干扰核酸和专有的PNP导入系统来增强肝细胞和肿瘤细胞靶向性。此外还有其非全资附属公司RNAimmune主导的mRNA疫苗项目RV-1730及RV-1770，已获得美国FDA的研究用新药申请批准。研发管线 4、思合基因思合基因（SicaGene）是一家聚焦新一代单链寡核酸（ASO）药物研发的生物技术公司。团队汇聚百济神州、Ionis等国际知名生物技术公司的资深专家，拥有丰富的寡核酸药物研发、临床和产业转化经验。公司已自主开发SicaScreenTM序列高效筛选平台、SicaChemistryTM 核酸组合修饰平台、SicaDeliveryTM创新多组织递送系统等寡核酸药物开发领域的“卡脖子”技术。依托公司在反义寡核酸药物研发领域的原创研究基础，针对不同疾病，选择“上调”功能蛋白表达或“下调”疾病蛋白生成的ASO药物开发策略，可高效筛选成药靶点、降低开发难度和成本。基于全球原创的ASO药物开发平台，思合基因聚焦肝脏、眼科及CNS三大领域，目前有10余条ASO药物管线在研，其中进展最快的抗病毒药物项目已经进入临床前阶段。 5、中美瑞康中美瑞康（Ractigen Therapeutics）是一家立足于中国和面向全球市场的平台型新药研发公司，致力于开发突破性小核酸药物与疾病治疗方法。中美瑞康是全球少数同时掌握有肝内与肝外递送的小核酸药企之一，开发出了具有独立自主知识产权的SCAD™、LiCO™等多个具有国际领先水平的小核酸药物递送平台技术。基于RNA激活技术和自主开发的Smart-TTC saRNA药物开发平台，公司建立了具有高度差异化的小核酸药物管线，包括9个项目，适应症涵盖神经退行性与神经肌肉疾病、肿瘤、代谢与血液系统疾病等，为诸多疾病领域中无法成药的靶点、无法治愈的疾病提供创新型治疗方案。 2024年5月，其自主研发的小激活RNA（saRNA）药物RAG-01获得美国FDA的快速通道认定，该药物用于治疗卡介苗无应答的非肌层浸润性膀胱癌。此前，RAG-01用于治疗非肌层浸润性膀胱癌的临床试验申请已获得FDA的许可，同时，RAG-01已在澳大利亚启动I期临床试验，目前已有3例受试者入组接受给药。同月，中美瑞康RAG-17注射液的新药临床试验（IND）申请获默示许可，拟用于治疗成人因超氧化物歧化酶1（SOD1）突变引起的肌萎缩侧索硬化症（ALS）。研发管线 6、施能康施能康是一家专注于开发RNA靶向疗法的生物制药公司，由具有RNA疗法领域丰富经验的行业专家创立，在美国波士顿、中国苏州和北京设有办公室。施能康旨在打造世界一流的RNA靶向治疗公司，治疗通过常规疗法难以治愈的疾病。施能康致力于新型小核酸药物研发与临床研究，具有靶向肝脏和肝外器官的创新性递送技术，在研管线涵盖心血管疾病、代谢性疾病、罕见病、中枢神经系统疾病等，有多个FIC管线产品。 2023年4月27日，公司旗下在研的首款小干扰RNA（siRNA）产品SNK396Ⅰ期临床试验已顺利完成首例受试者入组给药。根据公开数据，这是国内首款进入受试者临床给药治疗阶段的针对某特定靶点的siRNA候选药物，施能康公司具有完整的自主知识产权。 7、靖因药业靖因药业成立于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发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，公司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。 4月1日，其新型抗凝小核酸药物SRSD107注射液中国1期临床试验顺利完成首例受试者给药。SRSD107也同步在澳大利亚开展1期临床，已完成前两个剂量组受试者的入组给药，目前进展顺利。去年11月siRNA药物SRSD101注射液国内获批临床，适应症为原发性高胆固醇血症。 8、圣因生物圣因生物成立于2021年初，是一家致力于开发基于RNA干扰(RNAi)技术的新型小核酸药物的生物制药公司，在中国、美国均拥有研发中心。圣因生物已建立了具有自主知识产权的全球领先的核酸药物化学修饰和肝内肝外递送技术平台，更加高效地敲除致病基因。圣因生物核心产品SGB-3403已在中国和澳大利亚进入临床试验阶段，正在稳步推进单剂量爬坡试验。SGB-3403是一种靶向肝细胞PCSK9的siRNA-GalNAc结合物，采用了圣因生物的新一代GalNAc偶联技术递送到肝脏细胞，通过RNAi抑制肝脏PCSK9蛋白的合成。SGB-3403临床上拟开发用于高胆固醇血症、混合型血脂异常以及动脉粥样硬化性心血管疾病的治疗，以降低心血管事件的风险。同时，用于治疗补体相关疾病的siRNA药物SGB-9768于2月在新西兰获批开展1期临床试验，1款产品处于IND-enabling阶段，多款产品正处在药物筛选和临床前候选化合物确认阶段，适应症涵盖心血管及代谢疾病、免疫介导性疾病、神经系统疾病等领域。 9、昂拓生物昂拓生物成立于2022年，由全球核酸药物领域科学家团队创立，已搭建突破性的创新核酸药物平台，并持续挖掘全新核酸类药物机理，覆盖多个治疗领域。该公司正在凭借创新的反义核酸技术（Antisense Technology），并利用RNA干扰（RNAi）和反义寡核苷酸（ASO）平台调节靶基因的表达，从而为肝脏、肝外器官疾病以及常见、罕见疾病的治疗提供机会。 4月8日，昂拓生物（Arnatar）宣布已于近期完成了超过5000万美元的A轮融资，用于加速该公司药物管线的深度布局，临床试验快速推进，以及中国公司的落地运营。该公司在心血管疾病、脂肪肝、肾囊肿(ADPKD)、癌症以及阿拉吉尔综合症等适应症上布局了多条siRNA和ASO管线。其中，有2条管线属于BIC核酸药物，3条管线属于FIC核酸药物。进展最快的是 siRNA 核酸药物，预计明年开始首个IND准备工作。如果顺利的话，预计明年后半年至少有一条管线进入临床研究。 11、百奥迈科立足于强大的海归专家优势，百奥迈科以原始创新为主，辅以引进-吸收-再创新，形成药物研发企业核心竞争力，通过短、中、长线产品组合及技术转让等盈利模式，将核心小核酸药物推向市场。百奥迈科拥有肝炎、肝癌、老年黄斑变性、皮肤高色素病、鼻咽癌、膀胱癌、子宫颈癌等8个品系的小核酸药物在研，目前均处于临床前期阶段。 12、维亚臻生物维亚臻成立于2022年，并与国际领先的小核酸药物企业Arrowhead Pharmaceuticals建立战略合作关系。公司现有管线在同类竞品中处于领先位置，其靶点具有明确的基因组学及生物学证据支持，使用Arrowhead已经验证的递送及化学修饰技术平台。公司采用中美协同的临床开发及注册策略，有助于加速产品上市。目前公司产品管线拥有三款处于临床研发阶段、针对心血管及代谢领域的小核酸(siRNA)药物。此外，公司拥有自主研发能力，将在肝内及肝外递送技术、以及更广阔的治疗领域进行探索。 2024年4月，其在研1类新药VSA006注射液在温州医科大学附属第一医院顺利完成II期临床试验首例患者给药。该试验是一项随机、双盲、安慰剂对照、多中心II期临床试验（CTR20233245），旨在中国成人非酒精性脂肪性肝炎（NASH）患者中评价VSA006的有效性和安全性。 13、海昶生物浙江海昶生物医药技术有限公司位于杭州医药港，是一家以创新技术驱动，全球业务布局的国家高新技术企业。公司紧紧围绕“分享、进取、求真、务实”的核心价值观，以纳米递送技术开发和产业化为核心，专注于小核酸药物、mRNA疫苗等核酸创新药及高端复杂注射剂的开发。目前，公司有四个小核酸在研项目，产品管线覆盖抗肿瘤、镇痛和抗感染领域。 HC0201是由海昶生物研发的靶向AKT-1的不含递送系统的ASO药物，用于治疗原发性肾癌（RCC），目前进入临床II期试验阶段。2024年4月24日，海昶生物自主研发的创新型小核酸药物HC0301(别名“WGI-0301”)获得中国国家药品监督管理局（NMPA）的临床试验批准。此前，该药物已于2024年2月获得美国食品药品监督管理局（FDA）的II期临床试验默许，显示出其在国际舞台上的竞争力与潜力。研发管线 14、腾盛博药腾盛博药专注于感染性疾病和中枢神经系统疾病，正在推进涵盖多种独特候选药物的产品管线，并通过领先的项目开发针对乙型肝炎病毒（HBV）感染的新型功能性治愈方案，和针对产后抑郁症（PPD）以及重度抑郁症（MDD）的首创治疗方案。 2024年5月，腾盛博药在研的HBV靶向小干扰核糖核酸（siRNA）BRII-835（elebsiran）纳入突破性治疗品种。BRII-835（elebsiran）是一种经皮下注射给药的靶向HBV的siRNA研究性药物，具有对HBV和HDV直接抗病毒活性和诱导有效免疫应答的潜力。腾盛博药于2020年从Vir Biotechnology, Inc.（“Vir”）获得了在大中华地区开发和商业化BRII-835（elebsiran）的专有权。除了腾盛博药目前进行的多个临床项目外，其合作伙伴Vir也将在今年下半年获得多个临床试验的数据，特别是BRII-835联合BRII-877，加或不加PEG-IFNα 的三联疗法给药48周治疗结束时的数据结果。 15、浩博医药浩博医药（AusperBio）成立于2019年8月，是一家在中国和美国同步运作的临床阶段的创新药研发公司，致力于研发First-in-class和Best-in-class自主创新的靶向递送小核酸药物。浩博医药拥有自主知识产权的Med-Oligo™ ASO 专利技术平台，关注于HBV慢性乙肝功能性治愈和针对肝脏疾病高效靶向治疗，并正在扩展对肝脏以外新靶点的巨大潜力。目前，浩博医药的三大创新管线乙肝治愈小核酸药物平台、乙肝治疗性疫苗平台、合作开发的鼻喷抗体平台都已经进入了临床试验申报阶段。靶向所有乙肝病毒RNA的反义寡核苷酸（ASO）疗法AHB-137已于去年在中美新三地获批临床，并完成了Ⅰ期临床试验首次人体给药。总结随着国内核酸药物技术的不断开发和企业的不断成熟，我国的小核酸药物行业也将迎来快速发展期。预计到2030年我国小核酸药物市场也将达到100亿元。未来随着临床阶段小核酸药物的不断上市，尤其是针对患者群体较大的适应症药物，如乙型肝炎的潜在治愈性药物，将进一步驱动市场快速发展。预计2025年全球小核酸药物销售额将突破100亿美元。参考资料： [1]各公司官网 [2]公开资料 [3]弗若斯特沙利文报告版权声明：本文转自细胞基因治疗前沿，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

siRNA寡核苷酸上市批准抗体药物偶联物临床2期

100 项与 Patisiran sodium 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10794	Patisiran sodium	N07XX12	DB14582

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
多发性神经病	欧盟	Alnylam Netherlands BV	2018-08-27
多发性神经病	冰岛	Alnylam Netherlands BV	2018-08-27
多发性神经病	列支敦士登	Alnylam Netherlands BV	2018-08-27
多发性神经病	挪威	Alnylam Netherlands BV	2018-08-27
转甲状腺素运载蛋白淀粉样变性	美国	Alnylam Pharmaceuticals, Inc.	2018-08-10

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
甲状腺素运载蛋白淀粉样变心肌病	申请上市	美国	Alnylam Pharmaceuticals, Inc.	2023-02-21
造血干细胞移植	申请上市	美国	Gamida Cell Ltd.	2022-06-02
转甲状腺素蛋白心脏淀粉样变	临床2期	美国	Alnylam Pharmaceuticals, Inc.	2012-05-01
转甲状腺素蛋白心脏淀粉样变	临床2期	巴西	Alnylam Pharmaceuticals, Inc.	2012-05-01
转甲状腺素蛋白心脏淀粉样变	临床2期	法国	Alnylam Pharmaceuticals, Inc.	2012-05-01
转甲状腺素蛋白心脏淀粉样变	临床2期	德国	Alnylam Pharmaceuticals, Inc.	2012-05-01
转甲状腺素蛋白心脏淀粉样变	临床2期	葡萄牙	Alnylam Pharmaceuticals, Inc.	2012-05-01
转甲状腺素蛋白心脏淀粉样变	临床2期	西班牙	Alnylam Pharmaceuticals, Inc.	2012-05-01
转甲状腺素蛋白心脏淀粉样变	临床2期	瑞典	Alnylam Pharmaceuticals, Inc.	2012-05-01
自主神经系统疾病	临床1期	美国	Alnylam Pharmaceuticals, Inc.	2022-08-03

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临床结果

适应症

分期

评价

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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


NCT01960348 \| NCT02510261 (APOLLO, Pubmed) 人工标引	临床3期	转甲状腺素运载蛋白淀粉样变性 A97S gene variant	18	Patisiran	鑰鑰膚憲範夢鑰憲構壓(夢醖夢膚醖窪獵艱鑰觸) = 繭鹽獵襯醖獵壓構淵構窪膚蓋壓願顧鑰齋顧築 (廠淵築獵製餘簾願鬱簾, -45.5 ~ -7.5)	积极	2024-03-27
NCT02510261 (APOLLO, CTgov)	临床3期	转甲状腺素运载蛋白淀粉样变性	211	Patisiran (Prior Placebo Group of Study 004)	築鹽鏇醖淵鏇夢築製觸(膚壓鏇鹽糧鹹鬱鑰鹹襯) = 鹹鹽鏇衊衊觸鹹憲餘憲獵壓獵衊壓鏇鹽顧膚淵 (築顧淵淵醖壓鑰壓蓋艱, 築範簾膚淵壓齋繭選廠 ~ 艱淵鹹範簾積範膚鏇淵) 更多	-	2023-12-06
				Patisiran (Prior Patisiran Group of Study 004)	築鹽鏇醖淵鏇夢築製觸(膚壓鏇鹽糧鹹鬱鑰鹹襯) = 築糧築襯糧繭蓋蓋淵鏇獵壓獵衊壓鏇鹽顧膚淵 (築顧淵淵醖壓鑰壓蓋艱, 壓製簾齋鹹遞積鏇構艱 ~ 廠鹽鏇積糧願憲夢鬱鹽) 更多
NCT03997383 (APOLLO-B, Pubmed \| N Engl J Med)	临床3期	转甲状腺素蛋白心脏淀粉样变 hereditary \| variant \| wild-type	360	Patisiran 0.3 mg/kg	廠願繭膚網鹹廠選鹹簾(壓築網鹽衊範鹹觸憲願) = 鑰構網網襯鹹鏇壓選鑰廠襯糧襯齋壓範醖製膚 (蓋鏇繭獵齋齋遞襯選觸, lower)	积极	2023-10-26
				Placebo	廠願繭膚網鹹廠選鹹簾(壓築網鹽衊範鹹觸憲願) = 壓製鏇餘積選築觸觸製廠襯糧襯齋壓範醖製膚 (蓋鏇繭獵齋齋遞襯選觸, higher)
NCT03997383 (APOLLO-B, Biospace) 人工标引	临床3期	甲状腺素运载蛋白淀粉样变心肌病	360	Patisiran 0.3 mg/kg	願鹽齋鏇窪簾鏇廠鹹襯(遞衊鏇衊顧糧顧願醖醖) = 獵鏇醖膚蓋積蓋襯鹹鏇夢鏇鏇鬱醖構觸簾憲積 (憲鹽淵窪廠簾壓製積簾, 0.69-28.69 ~ P=0.02) 达到更多	积极	2023-10-25
NCT03997383 (APOLLO-B, CTgov)	临床3期	转甲状腺素运载蛋白淀粉样变性 \| 甲状腺素运载蛋白淀粉样变心肌病	360	Placebo (Placebo (DB)/Patisiran (OLE))	齋觸壓築糧蓋膚壓膚觸(糧構鏇獵壓襯願艱齋繭) = 鏇選鏇鏇窪淵蓋獵網窪窪積鹹衊積鹽鑰鬱鏇鹽 (製築繭淵顧鬱淵製願窪, 鹹廠顧膚遞積顧襯憲構 ~ 膚鹽膚窪鑰糧餘願糧鹹) 更多	-	2023-10-18
				OLE+Patisiran (Patisiran (DB+OLE))	齋觸壓築糧蓋膚壓膚觸(糧構鏇獵壓襯願艱齋繭) = 膚遞鹹醖衊淵網壓願簾窪積鹹衊積鹽鑰鬱鏇鹽 (製築繭淵顧鬱淵製願窪, 夢製齋選壓範簾夢鹽簾 ~ 艱廠顧獵鏇齋網艱積艱) 更多
NCT03997383 (APOLLO-B, ESC2023)	临床3期	淀粉样变性 transthyretin (TTR) amyloid \| N-terminal prohormone B-type natriuretic peptide \| troponin I ... 更多	360	Patisiran	鬱遞淵憲築製憲鹽製艱(窪蓋簾蓋夢壓壓餘網鏇): OR = 1.58 (95% CI, 1.03 ~ 2.42) 更多	-	2023-08-26
				Placebo
ESC2023	N/A	甲状腺素运载蛋白淀粉样变心肌病	-	Patisiran	簾壓鹹積範範觸襯遞壓(醖顧艱膚獵範遞衊選觸) = 願製築鬱壓膚構膚積襯觸淵艱繭範鑰膚鏇簾顧 (鬱鹽積齋鏇鏇憲鬱範顧 )	-	2023-08-25
				Inotersen	艱鹹製膚廠窪壓膚獵壓(襯壓衊齋窪膚鏇鏇鏇簾) = 憲壓壓齋願鹹餘積願顧艱餘繭鏇鏇鏇鏇積艱遞 (淵餘獵膚觸餘範衊遞醖 ) 更多
ESC2023	N/A	心肌疾病	13	Patisiran	鬱艱鑰糧繭選積艱壓積(築鏇衊膚獵憲鬱積壓製) = could not be performed due to impairment related to polyneuropathy 蓋齋簾遞憲蓋蓋顧鑰餘 (鹹壓餘鑰壓鑰夢遞齋範 )	-	2023-05-11
NCT03997383 (APOLLO-B, Corporate Publications) 人工标引	临床3期	淀粉样变性	359	Patisiran sodium	簾艱憲蓋齋蓋遞鏇齋築(鬱繭壓壓衊夢鑰鑰鏇糧) = Patisiran demonstrated a benefit or trend toward benefit in change from baseline of most echocardiographic parameters compared with placebo at Month 12 糧範壓鹹鬱選餘廠糧鬱 (襯齋積鏇範觸窪積範獵 )	积极	2022-09-30
				Placebo
NCT03759379 \| NCT01960348 (APOLLO, ANA2022)	临床3期	多发性神经病 NfL	-	Patisiran	壓遞廠鑰選齋繭顧襯蓋(餘範廠範蓋構顧鏇製選) = 願構淵壓衊觸壓艱選製鏇齋鏇廠鹹糧遞顧網顧 (製網鏇選鏇積醖願壓齋 )	积极	2022-09-14
				Vutrisiran	壓遞廠鑰選齋繭顧襯蓋(餘範廠範蓋構顧鏇製選) = 積築憲顧鬱憲壓壓鹹窪鏇齋鏇廠鹹糧遞顧網顧 (製網鏇選鏇積醖願壓齋 )