A Drug-Drug Interaction Study to Investigate the Effect of Givosiran on the Pharmacokinetics (PK) of Midazolam, Caffeine, Losartan, Omeprazole, and Dextromethorphan in Patients With Acute Intermittent Porphyria (AIP) Who Are Asymptomatic High Excreters (ASHE)

The purpose of this study is to evaluate the effect of givosiran on the pharmacokinetics of the 5-probe cocktail of midazolam, caffeine, losartan, omeprazole, and dextromethorphan, and their metabolites, in asymptomatic patients with Acute Intermittent Porphyria.

开始日期2018-04-26

申办/合作机构

Alnylam Pharmaceuticals, Inc.

NCT03338816

/ Completed临床3期

ENVISION: A Phase 3 Randomized, Double-blind, Placebo-Controlled Multicenter Study With an Open-label Extension to Evaluate the Efficacy and Safety of Givosiran in Patients With Acute Hepatic Porphyrias

The purpose of this study is to evaluate the effect of subcutaneous givosiran (ALN-AS1), compared to placebo, on the rate of porphyria attacks in patients with Acute Hepatic Porphyrias (AHP).

开始日期2017-11-16

申办/合作机构

Alnylam Pharmaceuticals, Inc.

100 项与 Givosiran Sodium 相关的临床结果

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100 项与 Givosiran Sodium 相关的转化医学

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100 项与 Givosiran Sodium 相关的专利（医药）

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项与 Givosiran Sodium 相关的文献（医药）

2024-12-06·Hematology-American Society of Hematology Education Program

Givosiran: a targeted treatment for acute intermittent porphyria

Review

作者: Leaf, Rebecca K. ; Dickey, Amy K.

Abstract:

The acute hepatic porphyrias (AHPs) are a family of rare genetic diseases associated with attacks of abdominal pain, vomiting, weakness, neuropathy, and other neurovisceral symptoms. Pathogenic variants in 1 of 4 enzymes of heme synthesis are necessary for the development of AHP, and the onset of acute attacks also requires the induction of δ-aminolevulinic acid synthase 1 (ALAS1), the first and rate-limiting step of heme synthesis in the liver. Givosiran is an RNA interference medication that inhibits hepatic ALAS1 and was designed to treat AHP. In 2019 the US Food and Drug Administration approved givosiran for AHP based on positive results from a phase 3 clinical trial of 94 patients with AHP who demonstrated a marked improvement in AHP attacks and a substantial decrease in δ-aminolevulinic acid and porphobilinogen, the primary disease markers of AHP. A long-term follow-up study demonstrated continued improvement in AHP attack rates, biochemical measures of disease, and quality of life. Real-world studies have also confirmed these results. Common side effects include injection site reactions, hyperhomocysteinemia, and abnormalities of liver and renal biochemistries. This article reviews the studies that led to givosiran approval, discusses real-world clinical data, and highlights remaining questions in the treatment of AHP.

2024-12-01·Revista clinica espanola

Therapeutic approach to acute crises of hepatic porphyrias

Review

作者: Pertusa Mataix, R. ; García Morillo, J.S. ; Garrido Montes, M. ; Garcia Morillo, J S ; Pertusa Mataix, R ; Garrido Montes, M

Acute hepatic porphyria is a genetic disorder affecting enzymes involved in heme biosynthesis. The most common subtype is acute intermittent porphyria, accounting for 80% of cases. Other types include hereditary coproporphyria, variegate porphyria, and delta-aminolevulinic acid dehydratase deficiency. Attacks in acute hepatic porphyria are triggered by the induction of hepatic ALA synthase 1, leading to the accumulation of neurotoxic heme intermediates, delta-aminolevulinic acid, and porphobilinogen. Women experience attacks more frequently than men. Acute porphyria attacks are characterized by severe, diffuse abdominal pain, muscle weakness, autonomic neuropathy (including hypertension, tachycardia, nausea, vomiting, and constipation), and changes in mental status. Early recognition of the disease is crucial as it requires urgent medical attention and treatment. Management includes intravenous opioids, glucose, hemin, and the removal of triggering factors. Preventive treatment options include hormone suppression therapy, off-label prophylactic hemin, Givosiran, and exceptionally liver transplantation.

2024-12-01·JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM

Neuralgic amyotrophy presentation of acute intermittent porphyria: A case report

Article

作者: Gouya, Laurent ; Durel, Cécile‐Audrey ; Pegat, Antoine ; Theuriet, Julian ; Gerfaud‐Valentin, Mathieu

Abstract:

Background and Aims:

Porphyrias are inherited metabolic disorders caused by mutations in genes encoding enzymes involved in the heme biosynthetic pathway, leading to the accumulation of heme precursors. Acute hepatic porphyrias (AHP), including acute intermittent porphyria (AIP), can present with predominant peripheral neurological manifestations, often leading to a misdiagnosis as Guillain‐Barré syndrome.

Methods:

We report a case of AIP initially presenting as a peripheral neuropathy mimicking Parsonage‐Turner syndrome (neuralgic amyotrophy, NA). Clinical and electrophysiological evaluations were conducted, including nerve conduction studies and needle electromyography (EMG).

Results:

A 41‐year‐old woman presented with burning pain and electric shock‐like sensations in the shoulders and trunk, alongside asymmetrical motor weakness in the upper limbs affecting arm abduction and finger extension. Electrophysiological evaluation revealed involvement of the superior trunk of the brachial plexus and the posterior interosseous nerve. Initially diagnosed with NA, she showed significant improvement in proximal strength over nine months but relapsed at fourteen months with severe finger extension weakness. Concurrent severe abdominal pain with constipation led to the identification of elevated urinary porphobilinogen (PBG) and delta‐aminolevulinic acid (ALA) levels, confirming AHP and specifically AIP via genetic and biochemical testing. The patient received hemin and givosiran infusions, resulting in decreased ALA levels, improvement of motor weakness, and no further attacks.

Interpretation:

This case underscores the need to consider AIP in the differential diagnosis of acute neuropathies like NA, especially when accompanied by abdominal pain and severe constipation. Early recognition and appropriate testing for PBG and ALA can prevent misdiagnosis and enable targeted treatment.

184

项与 Givosiran Sodium 相关的新闻（医药）

2024-12-10

·GlobeNewswire-Health Care

CAMP4 Appoints John Maraganore and Rachel Meyers as Strategic Advisors

Industry veterans John Maraganore, Ph.D., and Rachel Meyers, Ph.D., to provide strategic guidance on the company’s RNA Actuating platform to develop a new class of RNA medicines that upregulate protein coding genesCAMBRIDGE, Mass., Dec. 10, 2024 (GLOBE NEWSWIRE) -- CAMP4 Therapeutics Corporation (“CAMP4”) (Nasdaq: CAMP), a clinical-stage biotechnology company developing a pipeline of regRNA-targeting therapeutics designed to upregulate gene expression with the goal of restoring healthy protein levels across a range of genetic diseases, today announced the appointments of John Maraganore, Ph.D., and Rachel Meyers, Ph.D., as strategic advisors to the Company. For nearly 20 years, Dr. Maraganore served as the founding Chief Executive Officer and Director of Alnylam where he led the company’s programs in RNA interference through global commercialization, resulting in the launch of the first four RNAi therapeutics, ONPATTRO®, GIVLAARI®, OXLUMO®, and LEQVIO®. Additionally, Dr. Meyers brings more than two decades of life sciences leadership, research, and development experience in RNA-based medicines, having spent nearly 14 years at Alnylam where she most recently served as Senior Vice President of Research and RNAi Lead Development. She currently sits on the company’s Scientific Advisory Board. “We feel privileged and are delighted to welcome Drs. Maraganore and Meyers to our CAMP4 team as strategic advisors,” said Josh Mandel-Brehm, Chief Executive Officer of CAMP4. “We view their joining the team as a testament to the promise and potential of our approach for upregulating gene expression to potentially address a broad range of diseases. As we prepare for 2025, we look forward to benefiting from their insights and expertise as we advance our efforts in bringing potentially transformative RNA medicines to patients in need of disease-modifying solutions.” Dr. Maraganore added, “The targeted upregulation of gene expression has been a long-standing challenge for the field, and by applying established and clinically validated antisense oligonucleotide technology to groundbreaking science, CAMP4 could potentially make a meaningful impact on patients across a broad range of diseases. I look forward to working with them as they pioneer the field of upregulation.” Prior to his role at Alnylam, Dr. Maraganore led the product franchises in oncology, cardiovascular, inflammatory, and metabolic diseases for Millennium Pharmaceuticals, in addition to leadership of M&A, strategy, and biotherapeutics. Earlier in his career, Dr. Maraganore invented and spearheaded the development of ANGIOMAX® (bivalirudin) for injection while at Biogen and was also a scientist at ZymoGenetics, Inc., and the Upjohn Company. He currently serves as a Venture Partner at ARCH Venture Partners, a Venture Advisor at Atlas Ventures, an Executive Partner at RTW Investments, a Senior Advisor for Blackstone Life Sciences, and a Senior Advisor for Jeffries Financial Group. Beyond his leadership roles in the investment community, Dr. Maraganore also sits on the Board of Directors for multiple publicly traded companies, including Beam Therapeutics, Kymera Therapeutics, Rapport Therapeutics, and Takeda Pharmaceuticals. He received his B.A., M.S., and Ph.D. in biochemistry and molecular biology at the University of Chicago. Dr. Meyers currently serves as a member of the Board of Directors of Korro Bio (Nasdaq: KRRO), a biopharmaceutical company focused on discovering, developing, and commercializing a new class of genetic medicines based on editing RNA, and also holds a variety of advisory roles within the biotech community. Most recently, she served as Founder and Chief Scientific Officer at Faze Medicines, a Third Rock Ventures-spawned biotech company focused on treating diseases of high unmet need through the perturbation of biomolecular condensates. Earlier in her career, Dr. Meyers was a senior scientist at Millennium Pharmaceuticals and today serves on multiple scientific advisory boards, including the National Advisory Board on Innovation and Entrepreneurship through the Department of Commerce. Furthermore, she is listed as an inventor on numerous patents and patent applications and has authored many peer-reviewed publications. Dr. Meyers received her postdoctoral training with Lew Cantley at Harvard Medical School in signal transduction and earned her Ph.D. in biology from Nobel laureate Phil Sharp at the Massachusetts Institute of Technology in in vitro transcription. She earned her BA in Biochemistry from Brandeis University. “I’ve had the unique opportunity to work alongside tremendously talented professionals who have led the shaping of the RNA medicines space,” said Dr. Meyers. “Having been at the forefront of these scientific breakthroughs, I believe now more than ever RNA-based therapies are poised to continue transforming how we treat patients with complex diseases. Having the opportunity to advise CAMP4 as they continue advancing the field is an extension of the work to which I’ve committed my career.” About CAMP4 Therapeutics CAMP4 is developing disease-modifying treatments for a broad range of genetic diseases where amplifying healthy protein may offer therapeutic benefits. Our approach amplifies mRNA by harnessing a fundamental mechanism of how genes are controlled. To amplify mRNA, our therapeutic ASO drug candidates target regRNAs, which act locally on transcription factors and are the master regulators of gene expression. CAMP4’s proprietary RAP Platform™ enables the mapping of regRNAs and generation of therapeutic candidates designed to target the regRNAs associated with genes underlying haploinsufficient and recessive partial loss-of-function disorders, of which there are more than 1,200, in which a modest increase in protein expression may have the potential to be clinically meaningful. Learn more about us at www.CAMP4tx.com and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements which involve risks, uncertainties and contingencies, many of which are beyond the control of the Company, which may cause actual results, performance, or achievements to differ materially from anticipated results, performance, or achievements. All statements other than statements of historical facts contained in this press release are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning CAMP4’s plans, objectives, expectations and intentions; the timing and results of ongoing and future clinical trials, including expectations on the timing of reporting SAD and MAD data from and seeking regulatory approval for the CMP-CPS-001 trial; its growth strategy; and cash balance guidance. The forward-looking statements in this press release speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions that could cause the Company’s actual results to differ materially from those anticipated in the forward-looking statements, including, but not limited to: the Company’s limited operating history, incurrence of substantial losses since the Company’s inception and anticipation of incurring substantial and increasing losses for the foreseeable future; the Company’s need for substantial additional financing to achieve the Company’s goals; the uncertainty of clinical development, which is lengthy and expensive, and characterized by uncertain outcomes, and risks related to additional costs or delays in completing, or failing to complete, the development and commercialization of the Company’s current product candidates or any future product candidates; delays or difficulties in the enrollment and dosing of patients in clinical trials; the impact of any significant adverse events or undesirable side effects caused by the Company’s product candidates; potential competition, including from large and specialty pharmaceutical and biotechnology companies; the Company’s ability to realize the benefits of the Company’s current or future collaborations or licensing arrangements and ability to successfully consummate future partnerships; the Company’s ability to obtain regulatory approval to commercialize any product candidate in the United States or any other jurisdiction, and the risk that any such approval may be for a more narrow indication than the Company seeks; the Company’s dependence on the services of the Company’s senior management and other clinical and scientific personnel, and the Company’s ability to retain these individuals or recruit additional management or clinical and scientific personnel; the Company’s ability to grow the Company’s organization, and manage the Company’s growth and expansion of the Company’s operations; risks related to the manufacturing of the Company’s product candidates, which is complex, and the risk that the Company’s third-party manufacturers may encounter difficulties in production; the Company’s ability to obtain and maintain sufficient intellectual property protection for the Company’s product candidates or any future product candidates the Company may develop; the Company’s reliance on third parties to conduct the Company’s preclinical studies and clinical trials; the Company’s compliance with the Company’s obligations under the licenses granted to the Company by others, for the rights to develop and commercialize the Company’s product candidates; risks related to the operations of the Company’s suppliers; and other risks and uncertainties described in the section “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as well as other information we file with the Securities and Exchange Commission. The forward-looking statements in this press release are inherently uncertain and are not guarantees of future events. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond the Company’s control, you should not unduly rely on these forward-looking statements. The events and circumstances reflected in the forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Moreover, the Company operates in an evolving environment. New risks and uncertainties may emerge from time to time, and management cannot predict all risks and uncertainties. Investors, potential investors, and others should give careful consideration to these risks and uncertainties. Except as required by applicable law, the Company does not undertake to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contacts Investor Relations:Sandya von der WeidLifeSci Advisorssvonderweid@lifesciadvisors.com Media:Jason Braco, Ph.D.LifeSci Communicationsjbraco@lifescicomms.com

高管变更寡核苷酸

2024-12-10

·同写意

RNAi三巨头：不同战略下的云泥殊路

RNAi现象发现于上世纪90年代初期，早在1998年，科学家AndrewFire和CraigMello在线虫中首次揭示了RNAi现象，两人因此2006年获得诺贝尔生理医学奖。在诺奖的影响下，罗氏、默克、辉瑞、赛诺菲等大药厂纷纷进入RNAi领域。但随后却因siRNA的不稳定性、潜在的免疫原性及高效体内递送技术的缺乏，小核酸药物的发展一度在2009年至2013年陷入低谷期。经历过低谷期的Alnylam、Arrowhead、Dicerna等公司，纷纷潜心技术，在低谷期结束后，逐渐成长为RNAi领域的三巨头。从技术路线上看，三家企业专利多存在交叉授权，抑制效率，毒副作用等大同小异，适应症的选择也多有重合。三家企业之间的最主要区别在于同一适应症下，选择靶向的基因不同，以及临床执行能力的高低，而非技术方面的差异。但三家企业的发展却天壤之别，Alnylam业已成为市值300多亿美元的RNAi龙头企业，Dicerna及时卖身，给与股东回报，而Arrowhead迄今仍未有药物上市，市值仅为Alnylam的十分之一。 1 Alnylam：扛起RNAi疗法大旗 “Alnilam”是猎户座腰带中明亮的中心恒星，数千年来一直被用于航海导航的“宇宙灯塔”，这就是Alnylam公司名称的由来。自2002年成立之后，Alnylam一直致力于解决siRNA的递送问题，尝试了偶联物、脂质纳米颗粒、生物材料等多种递送方式，最终GalNAc成为了向肝脏递送寡核苷酸的主要技术，形成了公司的专利核心。在Alnylam潜心研发递送技术的同时，行业对RNAi领域的态度也由热转冷，罗氏、辉瑞、默沙东等大药企纷纷退出该领域，Alnylam的股价也跌入低点，不能不裁员续命。为了重获市场信心，Alnylam决定将发展重心从平台技术转移到管线研发，只要临床数据过硬，资金会再次涌入RNAi领域。2011年，Alnylam启动了“Alnylam5x15”的战略计划，意在在2015年底前将5个RNAi治疗药物推进到临床阶段。这次战略转向非常成功，到2015年末，Alnylam将8个项目推进临床阶段，并于2018年推出全球首款siRNA疗法ONPATTRO，自此之后，Alnylam实现了几乎每年一款新药的获批上市，至今，Alnylam已获得了五种RNAi药物的批准，包括patisiran、vutrisiran、givosiran、lumasiran（与诺华合作开发）和inclisiran。 2021年初，Alnylam又制定并启动“Alnylam p5×25”战略，重点计划在2025年底前成为市值排名前五的生物技术（Biotech）公司，具体而言，Alnylam打算在2025年结束时实现以下目标：在高目标的背后，是Alnylam超高临床转化率带来的自信。在临床1期至3期阶段，公司累计转化率达到64.4%，而行业整体的转化率只有5.7%，Alnylam是行业平均水平的11倍。与大部分biotech糟糕的商业化不同，Alnylam在药物销售方面表现优异。8月1日，Alnylam发布了2024年第二季度财报，上半年总收入11.54亿美元，同比增长80.9%；净产品收入7.75亿美元，同比增长33.2%，同时将全年业绩指引上调至15.75亿美元至16.5亿美元。除了良好的业绩，Alnylam在研发方面依然有着不俗的表现，仅在上半年就有多个突破：今年4月，Anlynam宣布了其针对肝脏表达的血管紧张素原（AGT）的研究型RNAi疗法Zilebesiran的KARDIA-2临床二期研究达到了主要终点和次要终点，具有令人鼓舞的安全性和耐受性，该疗法仅需一年两针，大幅提升了用药便利度；今年6月，公司公布了RNAi治疗药物vutrisiran的HELIOS-B临床三期研究达到了主要终点和所有次要终点。根据此积极结果，Alnylam将使用优先审评券向美国FDA递交补充新药申请。此外，Anlynam还在脑淀粉样血管病、2型糖尿病、阿尔海默兹症等领域进入临床阶段。借助RNAi技术平台，Anlynam每年申请2-4个研究性新药(IND)。鉴于高效的研发与出色的商业化能力，2020年，黑石生命科学（Blackstone Life Sciences）和Alnylam达成战略合作，黑石将提供高达20亿美元的资金来支持Alnylam开发创新RNAi疗法，治疗多种严重疾病患者。在一系列研发和销售成功的推进下，Anlynam的市值在过去十年间上涨了近6倍，产品收入几乎可以覆盖研发及管理费用，已经具备自我造血能力，成为RNAi领域名副其实的领头企业。 2 Arrowhead：战略失误下的千年老二趁着RNAi领域在2010年前后的艰难之际，Arrowhead通过收购罗氏、诺华的siRNA资产，获得关键专利技术储备，绕过Alnylam的专利限制，形成其专属的TRiM平台。 Arrowhead的TRiM平台的肝外递送能力则已经被初步验证，显示出应用于多个组织的潜力，如肺、肌肉、中枢神经系统等，看到了TRiM平台的潜力，Arrowhead开发了在肝病、心血管疾病及靶向肺部、肌肉、神经系统的研发管线，目前拥有16款在研管线，其中3款已进入临床III期：ARO-APOC3（Plozasiran）、ARO-ANG3、Fazirsiran。与Anlynam类似，Arrowhead也提出了“20 in 25”发展战略，计划在2025年将有20种合作或全资拥有的药物进入临床试验或上市。但与已经手握5款获批上市药物的Anlynam不同的是，Arrowhead还在证明自己的路上，临床研发执行效率成为Arrowhead发展的最大短板：一方面，临床进度缓慢，使得后续不断涌现的新技术对公司管线构成竞争，甚至来自同一RNAi领域的后起之秀，对公司形成威胁，如Avidity(NASDAQ:RNA)的市值已经超过Arrowhead；另一方面，缓慢的临床进度直接导致了自身造血能力的匮乏，这一点在Arrowhead的发展过程中体现的尤其明显。面对融资环境不佳，以及管线搁置等难题，Arrowhead选择了大量剥离资产，并以BD的形式获得融资。自2019年开始，Arrowhead便舍弃了原有股权融资的方式，开启靠BD维持企业运营的阶段，合作企业包括强生、GSK、安进、武田等MNC。过去两年，Arrowhead每年都能获得将近2亿美元的首付款。2023年财报显示，全年收入2.41亿美元，其中绝大部分收入来自于大药企的合作收入。但是，合作带来的收入规模无法满足同时拥有十几条在研管线的Arrowhead。过去两年，公司的现金消耗都在4亿美元以上。截至2023财年，账上现金只有4亿美元，仅能满足公司一年的发展需求。而Alnylam在2023年底便拥有超过24亿美元的现金，几乎与Arrowhead市值相当。以2019年开始就没有股权融资为自豪的Arrowhead，被迫于今年4月完成了一轮4.5亿美元的增发融资，增发价28.5美元/股。然而多条管线的开展依然让Arrowhead的资金吃紧，今年11月，Arrowhead宣布与Sarepta 达成全球许可和合作协议，其中首付款有8.5亿美元，未来5年获得等额分期付款2.5亿美元，并有望在未来12个月内实现目标并获得额外3亿美元近期付款，以及潜在100亿美元的里程碑付款。前有龙头企业Alnylam的快速发展，后有Avidity的迅猛追赶，长时间无法证明自己的Arrowhead难以获得资本市场的青睐，公司市值长期维持在30亿美元附近，不仅低于Avidity的40亿美元，而且仅为Alnylam的十分之一。不过Arrowhead已于今年11月递交了plozasiran上市申请，用于治疗家族性乳糜微粒血症综合征 (FCS)，即将进入的商业化，看能否成为改变Arrowhead命运的变量。 3 Dicerna：及时卖身的行业老三 Dicerna制药(NASDAQ:DRNA)成立于2007年，也是一家RNAi疗法企业，拥有能够实现肝脏靶向（GalXC™）和肝外靶向（GalXC-Plus™）的递送平台。 Dicerna的主要管线是用于治疗原发性高草酸尿综合征（PH）的nedosiran，而行业老大哥Alnylam当时也在开发PH的RNAi药物，当时已经申请NDA了，比DRNA至少快2年。为了形成差异化，不同于Alnylam药物主要靶向GO基因，Dicerna的nedosiran靶向LDHA（乳酸脱氢酶A），对某些亚型的PH患者有差异化优势。此外，公司还布局了α-1抗胰蛋白酶缺乏症导致的肝损伤（AATD-LD）、乙肝等适应症。自2019年以来，诺和诺德和Dicerna保持者合作伙伴关系，前者利用Dicerna专有的技术平台开发RNAi疗法，合作范围包括对30多个肝细胞靶标的探索，有可能为包括慢性肝病、非酒精性脂肪性肝炎（NASH）、2型糖尿病、肥胖和罕见疾病在内的疾病提供多种临床候选药物，而这些领域都是诺和诺德的发展方向。 2021年11月，诺和诺德宣布以33亿美元的价格收购Dicerna，折合每股收购价为38.25美元，溢价80%。对于细分领域无法成为前两名的企业而言，在行业热度较高时，及时被收购是不错的选择。 2023年9月，FDA批准诺和诺德RNAi疗法Nedosiran上市，用于降低9岁及以上儿童和成人1型原发性高草酸尿症（PH1）患者的尿草酸水平，并于2024年正式上市。 4 投资警示：赛道与技术之外的因素处于同一赛道的三家RNAi企业，都经历了行业的高潮低估，技术路线有差异，却无明显的水平高下之分，但因发展方向、执行能力等方面的差异，导致公司发展局面迥然：近五年来，Alnylam市值增长1.5倍，Dicerna市值增长2倍，而Arrowhead的市值却跌去三分之二。对于投资人而言，在选定赛道与技术的基础上，还要看企业的战略与执行能力，后者不仅是充分发挥技术潜力的重要保障，而且是产生股东回报的重要条件。同写意媒体矩阵，欢迎关注↓↓↓

siRNA临床3期上市批准核酸药物临床2期

2024-11-25

·Business Wire

Alnylam Announces U.S. Food and Drug Administration Acceptance of Supplemental New Drug Application for Vutrisiran for the Treatment of ATTR Amyloidosis with Cardiomyopathy

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Company’s supplemental New Drug Application (sNDA) for vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). Based on the Company’s use of a Priority Review Voucher, the FDA has set an action date goal of March 23, 2025, under the Prescription Drug User Fee Act (PDUFA). The FDA has informed the Company that it is not planning to hold an advisory committee meeting at this time to review the application. Vutrisiran is the generic name for AMVUTTRA ® , which is currently approved by the FDA for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. By rapidly knocking down both mutant and wild‑type transthyretin (TTR), vutrisiran addresses the underlying cause of transthyretin amyloidosis (ATTR). If approved, vutrisiran would become the first therapeutic approved in the U.S. to treat both the polyneuropathy manifestations of hATTR and cardiomyopathy manifestations of ATTR amyloidosis. “We are pleased that the FDA has accepted our sNDA for vutrisiran for the treatment of ATTR with cardiomyopathy – a steadily progressing, debilitating and ultimately fatal disease,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “In HELIOS-B, treatment with vutrisiran improved cardiovascular outcomes, survival, disease progression and quality of life, as compared to placebo, in a population reflective of today’s patients on substantial background treatment. We look forward to working with the FDA to support their review of the application and bring vutrisiran to patients with ATTR-CM in the U.S. early next year.” The supplemental application to the FDA was based on positive results from HELIOS-B, a randomized, double-blind, placebo-controlled multicenter global Phase 3 study in patients with ATTR-CM. The study demonstrated favorable effects of vutrisiran on outcomes of death and cardiovascular events, functional capacity and quality of life in patients with ATTR-CM. These treatment effects were seen on top of substantial background standard of care treatments. Vutrisiran demonstrated encouraging safety and tolerability consistent with the established profile of the drug. Detailed results from the study were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine on August 30, 2024. AMVUTTRA ® (vutrisiran) U.S. Indication and Important Safety Information Indication AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. Important Safety Information Reduced Serum Vitamin A Levels and Recommended Supplementation AMVUTTRA treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness). Adverse Reactions The most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%). For additional information about AMVUTTRA, please see the full U.S. Prescribing Information . About AMVUTTRA ® (vutrisiran) AMVUTTRA ® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of mutant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, AMVUTTRA is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease. For more information about AMVUTTRA, including the full U.S. Prescribing Information , visit AMVUTTRA.com . About ATTR Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000 – 300,000 people worldwide. About RNAi RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors that encode for disease-causing or disease pathway proteins – thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam (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 . Alnylam Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, Alnylam’s expectations regarding the safety and efficacy of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy, including the safety, tolerability and favorable effects of vutrisiran on outcomes of death and cardiovascular events, functional capacity and quality of life in patients with ATTR-CM; whether the FDA will convene an advisory committee in connection with the FDA’s review of Alnylam’s supplemental application for approval of vutrisiran for the treatment of patients with ATTR-CM; the potential for vutrisiran to obtain FDA approval for the treatment of patients with ATTR-CM, and the anticipated timing of such FDA approval; and the potential for Alnylam to achieve its Alnylam P 5 x25 vision of becoming a leading biopharma company should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “ Alnylam P 5 x25 ” strategy; Alnylam’s ability to successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including vutrisiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain regulatory approval for its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; and any delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2023 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q and in its other SEC filings. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

临床结果上市批准临床3期申请上市优先审批

100 项与 Givosiran Sodium 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11702 D11708	Givosiran Sodium	J05AB	DB15066

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
肝性卟啉症	加拿大	Alnylam Pharmaceuticals, Inc.	2020-12-01
急性肝卟啉症	美国	Alnylam Pharmaceuticals, Inc.	2019-11-20

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
遗传性类卟啉症	临床3期	美国	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	日本	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	澳大利亚	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	保加利亚	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	加拿大	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	丹麦	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	芬兰	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	法国	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	德国	Alnylam Pharmaceuticals, Inc.	2017-11-16
遗传性类卟啉症	临床3期	意大利	Alnylam Pharmaceuticals, Inc.	2017-11-16

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临床结果

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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


NCT02949830 (CTgov)	临床1/2期	急性间歇性卟啉病	16	Givosiran	鹹鏇範壓憲鏇簾積襯積(鬱願淵觸構遞選窪襯襯) = 艱鏇製網選艱夢鬱窪糧蓋憲製壓製築網願壓鹽 (鬱構鹹淵廠廠淵襯顧築, 衊蓋鹹衊鏇餘餘構鬱壓 ~ 觸築觸鏇衊醖積餘醖積) 更多	-	2024-03-12
EHA2023	N/A	多样性卟啉病	-	Givosiran	鹹廠淵齋願選窪築齋艱(顧網襯襯糧醖獵簾顧製) = 鏇製範製鏇選築蓋艱觸衊憲範觸鏇鹽蓋鑰衊餘 (淵顧夢範遞鑰積願鹽製 ) 更多	-	2023-06-08
NCT03338816 (ENVISION, Pubmed \| Liver Int) 人工标引	临床3期	急性肝卟啉症	94	Givosiran Sodium	構選夢鑰顧醖範鬱製簾(遞壓願窪鹹鹽遞遞製積) = 鏇醖鑰鬱繭齋積淵範壓廠鏇製膚遞顧醖鑰製壓 (糧獵鹹衊構繭壓鏇憲餘 ) 更多	积极	2021-10-30
NCT03338816 (ENVISION, Pubmed \| Liver Int) 人工标引	临床3期	急性肝卟啉症	94	Placebo+Givosiran Sodium	構選夢鑰顧醖範鬱製簾(遞壓願窪鹹鹽遞遞製積) = 糧衊襯遞襯齋鑰範網壓廠鏇製膚遞顧醖鑰製壓 (糧獵鹹衊構繭壓鏇憲餘 ) 更多	积极	2021-10-30
EASL2020	临床1/2期	急性间歇性卟啉病 5-aminolaevulinic acid synthase 1 (ALAS1)	-	Givosiran	顧壓鹽淵築鏇顧壓衊製(鑰蓋範範繭膚廠糧願簾) = 顧觸選獵蓋築醖顧糧憲襯構淵齋構鏇鏇鬱鹹獵 (蓋鬱繭繭鏇鬱願構襯製 ) 更多	-	2020-08-27
NCT03338816 (ENVISION, Pubmed \| Br Dent J \| N Engl J Med) 人工标引	临床3期	急性间歇性卟啉病	94	Givosiran	襯鬱觸鬱餘積齋築製鑰(衊齋齋齋顧顧鑰簾齋衊) = 醖窪繭構遞齋淵襯憲築憲艱壓築構遞鑰鏇艱壓 (壓範繭夢積淵鹹顧淵衊 )	积极	2020-06-11
	临床3期	急性间歇性卟啉病	94	Placebo	襯鬱觸鬱餘積齋築製鑰(衊齋齋齋顧顧鑰簾齋衊) = 鑰築積淵選簾憲顧製顧憲艱壓築構遞鑰鏇艱壓 (壓範繭夢積淵鹹顧淵衊 )	积极	2020-06-11
NCT03338816 (ENVISION, CTgov)	临床3期	急性肝卟啉症 \| 多样性卟啉病 \| 急性间歇性卟啉病 ... 更多	94	Placebo+Givosiran (Placebo/Givosiran)	憲鬱顧醖遞艱構膚鏇鹽(簾繭夢衊壓淵窪夢獵餘) = 醖艱鏇壓膚廠艱築構範鏇餘襯蓋積網齋鹹醖蓋 (鏇壓襯鬱憲膚鹽窪壓顧, 鑰窪顧餘願鹹襯構淵膚 ~ 簾憲餘製顧積遞選鏇衊) 更多	-	2020-02-11
NCT03338816 (ENVISION, CTgov)	临床3期	急性肝卟啉症 \| 多样性卟啉病 \| 急性间歇性卟啉病 ... 更多	94	Placebo+Givosiran (Givosiran/Givosiran)	憲鬱顧醖遞艱構膚鏇鹽(簾繭夢衊壓淵窪夢獵餘) = 構鑰製艱簾顧遞範夢築鏇餘襯蓋積網齋鹹醖蓋 (鏇壓襯鬱憲膚鹽窪壓顧, 蓋遞獵範窪淵糧築窪構 ~ 繭製繭積窪壓築廠簾鏇) 更多	-	2020-02-11
EAN2019	临床1/2期	ALAS1	-	Givosiran 2.5 mg/kg	憲鹽範壓選鬱糧襯壓鬱(選夢憲簾廠願鬱選醖壓) = 觸繭鏇壓衊壓淵鹹繭鬱襯餘構齋齋簾顧鹹選積 (顧鹹築壓遞顧鬱餘淵鹹 ) 更多	积极	2019-06-27
EAN	N/A	急性间歇性卟啉病	-	Givosiran 2.5mg/kg	鏇觸製簾膚製製膚網鹹(膚積觸鏇餘鏇鑰遞觸糧) = One unexpected serious adverse event (SAE; hypersensitivity) related to Givosiran occurred 願願範網餘繭遞鹽夢鬱 (鏇壓積廠獵構鹹鹹選獵 ) 更多	-	2018-06-14