Phase 3 Study to Evaluate the Efficacy and Safety of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)

This multicenter, randomized, placebo-controlled study will evaluate the efficacy and safety of zodasiran subcutaneous (SC) injection in subjects 12 years of age and older with genetically or clinically diagnosed Homozygous familial hypercholesterolemia (HoFH). After completion of the double blind (DB) treatment period subjects will be eligible to continue in the optional open-label extension (OLE) period of the study. All placebo subjects who opt to continue will transition to active drug during the OLE Period.

开始日期2025-06-17

申办/合作机构

Arrowhead Pharmaceuticals, Inc.

NCT06937203

/ Recruiting临床1/2期

A Phase 1/2A Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ARO-ALK7 in Adult Volunteers With Obesity With and Without Type 2 Diabetes Mellitus

This study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of ARO-ALK7 in adult volunteers with obesity without Type 2 Diabetes Mellitus (T2DM) (Part 1) and the safety, tolerability, and PD of multiple doses of ARO-ALK7 in adult volunteers with obesity with and without (T2DM) receiving tirzepatide (Part 2). In Part 1A eligible participants with obesity will be randomized to receive a single dose of ARO-ALK7 or placebo (PBO) administered on Day 1. In Part 1B, eligible participants with obesity will be randomized to receive two doses of ARO-ALK7 or PBO administered on Day 1 and Day 85. In Part 2, eligible subjects with obesity with and without (T2DM) will randomized to combined therapy with tirzepatide and ARO-ALK7 (intervention arm) or tirzepatide and PBO (control arm). Tirzepatide will be initiated on Day 15 and administered by subcutaneous (SC) injection weekly. ARO-ALK7 or PBO will be administered by SC injection on Day 1 and Day 85. Subjects in both Part 1 and Part 2 will undergo adipose aspiration pre and post dose.

开始日期2025-05-07

申办/合作机构

Arrowhead Pharmaceuticals, Inc.

NCT06822790

/ Recruiting临床3期

A Phase 3 Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia (SHASTA-10 Study)

This is an open-label study to be conducted in adults with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (SHTG). Each participant must have completed all required visits per protocol in the parent study AROAPOC3-3001 (NCT05089084), AROAPOC3-3003 (NCT06347003), AROAPOC3-3004 (NCT06347016) or AROAPOC3-3009 (NCT06347133). All eligible participants will receive plozasiran administered subcutaneously (SC) approximately every 3 months for 24 months. Participants will be counseled to remain on the specified low-fat diet throughout the study in accordance with local standard of care.

开始日期2025-04-09

申办/合作机构

Arrowhead Pharmaceuticals, Inc.

100 项与 Arrowhead Pharmaceuticals, Inc. 相关的临床结果

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0 项与 Arrowhead Pharmaceuticals, Inc. 相关的专利（医药）

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项与 Arrowhead Pharmaceuticals, Inc. 相关的文献（医药）

2025-09-01·JOURNAL OF PHARMACEUTICAL SCIENCES

Strategies for the evaluation and characterization of higher-order structures, supramolecular higher-order structures, and aggregates in oligonucleotide therapeutics

Review

作者: Cui, Lingwen ; Elmekawy, Ahmed ; Farzan, Maryam ; Carloni, Laure-Elie ; Yin, Haiqing ; Nazir, Zahid ; Bou-Assaf, George ; Shi, Eric ; Rieder, Ulrike ; Chanda, Arani ; Joyce, Leo ; Majumdar, Ranajoy ; Zhang, Yueheng

Synthetic oligonucleotides have emerged as a promising therapeutic class, holding significant potential for the treatment of a wide range of indications, including previously undruggable targets. Due to specific primary structure motifs, oligonucleotide therapeutics may form higher-order structures (HOS), supramolecular higher-order structures (sHOS) and/or aggregates, which are influenced by factors such as dissolution medium and oligonucleotide concentration. Although rarely observed, unintended (s)HOS and/or aggregates might influence various stages of drug substance (DS) or drug product (DP) manufacturing. There is no published guidance on how to best approach the characterization of oligonucleotide therapeutics (s)HOS and aggregation in a scientific and systematic manner. In this article, we provide an overview of oligonucleotide therapeutics (s)HOS formation and aggregation behavior. Based on industry experience and available literature, we also propose strategies for their evaluation and characterization under relevant conditions. The recommended approach involves conducting appropriate scientific assessments during product development with the support of designed workflows, which can help anticipate and/or mitigate the formation of unintended species.

2025-06-13·JCEM Case Reports

Glycerol Kinase Gene Variant as a Cause of Pseudohypertriglyceridemia and Apparent Poor Response to Plozasiran

Article

作者: Dufour, Josiane ; Larouche, Miriam ; Ballantyne, Christie ; Given, Bruce ; Gaudet, Daniel ; Brisson, Diane

Abstract:

Severe hypertriglyceridemia (HTG) is characterized by plasma triglyceride (TG) levels >500 mg/dL (SI: 5.7 mmol/L) (reference range, <150 mg/dL [SI: <1.7 mmol/L]) and is linked to cardiovascular disease and pancreatitis risk. Treatment typically involves dietary restrictions and lipid-lowering medications. Glycerol kinase deficiency (GKD) is a rare genetic disorder that causes pseudo-HTG.In SHASTA-2, a study of patients with severe HTG, most subjects (>90%) treated with plozasiran, an apolipoprotein C-III (APOC3) small interfering RNA (siRNA), achieved TG levels <500 mg/dL (SI: 5.7 mmol/L), below the risk threshold for acute pancreatitis. We report herein a case study of a 65-year-old male apparently not responding to plozasiran. The patient was shown to carry a loss-of-function variant in the GK gene resulting in GKD, with high free glycerol (40.24 mg/dL or 4.37 mmol/L) (reference range, 0.03-0.13 mmol/L) that contributed to an overestimation of TG concentration. After correcting for free glycerol, the patient was noted to have had mild HTG, with plozasiran treatment decreasing real TG values by up to 71%.This case report suggests that in the absence of response to APOC3 inhibition, measuring free glycerol could be clinically relevant. It also highlights that APOC3 inhibition has no effect on free glycerol concentration.

2025-05-01·JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Effect of Targeting ApoC-III With Plozasiran on Lipoprotein Particle Size and Number in Hypertriglyceridemia

Article

作者: Zhou, Rong ; Hegele, Robert A ; Gaudet, Daniel ; Rosenson, Robert S ; Ballantyne, Christie M ; Hellawell, Jennifer ; Melquist, Stacey ; Leeper, Nicholas J

BACKGROUND:

Plozasiran, an investigational siRNA targeting hepatic apoC-III, reduces triglyceride-rich lipoproteins (TRLs). The impact of plozasiran on lipoprotein particle numbers and sizes is unknown. However, reductions in the number of TRL particles (TRL-P) and a shift to possibly less atherogenic large low-density lipoprotein particles (LDL-P) are expected.

OBJECTIVES:

This study aimed to determine the impact of plozasiran on lipoprotein particle concentration and subclass distribution using nuclear magnetic resonance (NMR) in 2 phase 2 studies.

METHODS:

Patients (N = 403) from SHASTA-2 (severe hypertriglyceridemia) and MUIR (mixed hyperlipidemia) were administered 2 total subcutaneous doses of plozasiran (10, 25, or 50 mg) or placebo at baseline and week 12. Comprehensive lipoprotein profiling was conducted with NMR.

RESULTS:

In SHASTA-2, there was a dose-dependent reduction in TRL-P, with placebo-adjusted total TRL-P reductions of -46% and reductions across all TRL subclasses with plozasiran. While total LDL-P was unchanged, large LDL-P concentration increased by +53% and medium by +56%; small LDL-P trended lower (-13%). Total HDL-P increased by +8%, primarily driven by a +36% increase in large high-density lipoprotein particles (HDL-Ps). Similarly, in MUIR, there were dose-dependent reductions in TRL-P, with total TRL-P significantly reduced by -48% (pooled plozasiran) and reductions across all TRL subclasses with plozasiran. While total LDL-P was unchanged, large and medium LDL-P levels increased by +88% and +46%, respectively; small LDL-P levels decreased by -28%. Total HDL-P increased by +12%, driven by a +83% increase in large HDL-P.

CONCLUSIONS:

Plozasiran induced reductions in apoC-III and showed potentially favorable quantitative and qualitative changes in lipoproteins as assessed by NMR in patients with hypertriglyceridemia and mixed hyperlipidemia. Plozasiran reduced TRL-P by ∼50%, shifted LDL to larger particles, and modestly increased HDL-P concentration. While high-potency TRL-lowering therapies can lead to an overall LDL-C increase, plozasiran did not increase LDL-P or apoB but shifted LDL particle size distribution from small dense LDL toward larger sizes. The ∼50% reduction in TRL-P with no increase in apoB and possibly beneficial qualitative changes in LDL suggests the potential of plozasiran to lower cardiovascular risk, which may be evaluated in a prospective outcomes trial.

587

项与 Arrowhead Pharmaceuticals, Inc. 相关的新闻（医药）

2025-08-21

·EndPoints

Sarepta refinances its debt; FDA delays decisions on Eylea HD

Plus, news about Benchling, Invivyd, Immuneering, Scilex and Sana Biotechnology: 📉 Sarepta’s debt refinancing: The biotech, which went through a complicated exchange with the FDA this summer over the safety of its Duchenne gene therapy, will extend its debt from 2027 to 2030 to improve its finances. “By extending the maturity of a meaningful portion of our convertible notes to 2030, we have completed a shareholder-friendly transaction,” CEO Doug Ingram said in a statement. Last week, the company had to sell its stock position in Arrowhead Pharmaceuticals to be able to pay a milestone fee to Arrowhead, which has siRNA programs that could drive the future of Sarepta’s pipeline under a $10 billion biobuck pact . — Kyle LaHucik 🏭 As expected, Regeneron says FDA decisions on Eylea HD are delayed: The regulator pushed back two decisions on Eylea’s high-dose formulations to the fourth quarter. The original decision date was Aug. 19. Regeneron is seeking approval for a pre-filled syringe, treatment for macular edema following retinal vein occlusion, and a broader dosing schedule for all indications. It previously disclosed that it expected delays following an inspection of a third-party manufacturer site in Indiana, formerly owned by Catalent and now part of Novo Nordisk. Scholar Rock , another customer of the Indiana site, has said it doesn’t expect any PDUFA delays for its experimental spinal muscular atrophy drug called apitegromab. — Anna Brown 💻 Benchling’s two deals: The life sciences software startup “acquired the teams” of ReSync Bio and Sphinx Bio. The startups create “AI tools that power scientific workflows,” Benchling said. Earlier this year, Benchling laid off 10% of its staff. The San Francisco-based company partners with biopharmas like Merck and Moderna on AI research, bioanalytics and other functions. It raised a $100 million Series F in 2021. — Kyle LaHucik 💰 Invivyd’s $50M stock sale: The company, which has an authorized Covid-19 prevention drug called Pemgarda, is selling 21.3 million shares at 52 cents apiece. — Jaimy Lee 🏥 Immuneering gets $25M from PIPE: The company said it expects to share updated overall survival and progression-free survival data from its Phase 2a trial of atebimetinib in pancreatic cancer “in the coming weeks.” — Jaimy Lee 💵 Scilex raises $20M for Phase 3 trial: Semnur Pharmaceuticals, Scilex’s parent company, and Denali Capital inked the private placement with an unnamed investor to help advance Scilex’s SP-102 into a second Phase 3 trial for lumbar radicular pain, or sciatica. — Jaimy Lee 💸 Sana Biotechnology ended up raising $86.3 million, up from the $75.0 million it intended to bring in. — Jaimy Lee

临床2期并购临床3期

2025-08-20

·研发客

又一siRNA公司获千万美金种子轮融资！自研肝外递送平台

据杏泽资本透露，蔚程医药有限公司（Vivatides Therapeutics, 下称蔚程医药）日前完成由杏泽资本领投、启明创投跟投的千万美金种子轮融资。资金主要用于临床前肝外靶向小核酸平台及管线开发。全球小核酸药物市场规模快速增长，有望成为小分子和抗体以后的第三大类药物。目前商业化阶段的siRNA药物均为肝靶向，技术较为成熟，但肝外市场有巨大需求和拓展空间。肝外靶向递送在受体选择、吸收效率、安全性等方面有挑战，化学修饰也在迭代，它是小核酸技术下一代发展方向，而突破者将占市场先机。根据新闻稿，蔚程医药自主研发的肝外递送平台，在底层设计上具备差异化创新，旨在突破肝外靶向的瓶颈。蔚程医药创始人周科明博士表示：“肝外靶向递送是小核酸技术公认的下一代发展方向。我们创立蔚程医药的初心，是希望发展创新的递送技术平台，使小核酸药物能够更精准地作用于多种非肝脏组织，从而覆盖更广泛的疾病领域，让多元化的小核酸疗法惠及更多患者。” 蔚程医药仅成立几个月，核心团队来自Arrowhead、Ionis、Alnylam、Dicerna等小核酸头部企业，有多年肝外管线开发经验。创始人周科明博士曾在Arrowhead、Ionis领导了多个肝外小核酸管线的开发和相关平台的建立。他表示，创立公司是希望发展创新递送技术平台，让小核酸药物覆盖更多疾病领域，团队成员曾主导或者深度参与多个肝外管线开发。公司自主研发的肝外递送平台有差异化创新，是少数兼具肝外ASO和siRNA实际管线开发经验的技术团队。杏泽资本管理合伙人强静博士表示：“小核酸肝外靶向递送方向一直是杏泽资本重点关注的方向。我们相信小核酸肝外递送技术突破将使重大慢病和"不可成药"靶点迎来治疗范式革新。周科明博士及其团队在海外小核酸龙头企业深耕多年，积累了丰富的肝外小核酸药物的研发和工艺经验。公司成立数月以来，已在肝外递送平台与管线方面取得了令人振奋的阶段性成果，并在动物实验中实现了实质性进展。” 除了投资蔚程医药，杏泽资本还参与了舶望制药和昂拓生物投资。舶望制药在肝外靶向研发方面已有多个项目进入临床前研究；昂拓生物开发新型递送系统，杏泽资本为其提供资金支持。启明创投紧跟行业趋势，关注创新成长性企业。启明创投也参与了蔚程医药融资，显示其看好肝外靶向领域，同时能为企业提供战略指导和资源支持。启明创投合伙人、医疗健康行业共同负责人陈侃博士表示蔚程医药在小核酸肝外靶向递送技术领域所取得的进展，令人印象深刻。该平台技术有望为众多目前缺乏有效治疗手段的肝外组织疾病解锁全新的治疗机会。近期中国小核酸药物领域融资活动频繁，多家公司获得了新的资金支持。2025年4月，炫景生物获得Pre-A轮融资，浩博医药2025年5月开展了B+轮融资，获得了5000万美元，靖因药业2025年5月获得近5000万美元的B轮融资，2025年8月，海昶生物获得近5亿元人民币的C轮融资，瑞博生物也是在今年8月获得私募股权融资逾2亿元人民币等。小核酸药物领域近期备受资本青睐，业内分析认为，包括肝靶向递送技术的突破和成功应用，证明了小核酸药物的潜力，小核酸药物在慢性疾病管理的巨大的市场以及交易与合作活跃令资本加注这一领域。总第2542期访问研发客网站，深度报道和每日新闻抢鲜看 www.PharmaDJ.com

siRNA核酸药物

2025-08-20

·动脉网

【首发】蔚程医药完成千万美金种子轮，剑指肝外靶向小核酸蓝海

动脉网第一时间获悉，近日，蔚程医药有限公司（Vivatides Therapeutics, 以下简称“蔚程医药”）宣布完成杏泽资本领投，启明创投跟投的千万美金种子轮融资。本轮募资资金主要用于临床前肝外靶向小核酸平台及管线的开发。随着一系列小核酸重磅品种商业化的不断突破，小核酸药物全球市场规模正快速增长，有望成为小分子和抗体后的第三大类药物。截至目前处于商业化阶段的siRNA药物均为肝靶向品种，肝外市场存在极大的未尽需求和可拓展空间。相较于肝靶向成熟的GalNac递送方式，肝外靶向递送在递送受体选择及配体偶联、目标组织吸收效率、安全性上都有较大的挑战，化学修饰仍在不断迭代中。蔚程医药自主研发的肝外递送平台，在底层设计上具备差异化创新，旨在突破肝外靶向的瓶颈。蔚程医药成立于2025年，公司国际化核心团队成员创立公司前在小核酸行业头部公司包括Arrowhead、Ionis、Alnylam、Dicerna具有多年研发经验，曾主导或者深度参与多个肝外管线开发，多个项目当前处于临床开发阶段，是少数兼具肝外ASO和siRNA实际管线开发经验的技术领军团队。创始人周科明博士曾在Arrowhead、Ionis领导了多个肝外小核酸管线的开发和相关平台的建立。蔚程医药创始人周科明博士表示：“肝外靶向递送是小核酸技术公认的下一代发展方向。我们创立蔚程医药的初心，是希望发展创新的递送技术平台，使小核酸药物能够更精准地作用于多种非肝脏组织，从而覆盖更广泛的疾病领域，让多元化的小核酸疗法惠及更多患者。衷心感谢杏泽资本和启明创投的信任与大力支持。公司团队正全力加速平台优化与管线布局，我们将持续在全球小核酸药物研发的前沿探索、前进，并贡献我们的力量。” 杏泽资本管理合伙人强静博士表示：“杏泽资本致力于支持能解决未被满足的重大临床需求的创新生物医药公司，小核酸赛道作为设立投资人参与了舶望制药和昂拓生物，小核酸肝外靶向递送方向一直是杏泽资本重点关注的方向。我们相信小核酸肝外递送技术突破，将为重大慢病和‘不可成药’靶点带来治疗范式革新。周科明博士及其团队在海外小核酸龙头企业深耕多年，积累了丰富的肝外小核酸药物的研发和工艺经验。公司成立数月以来，已在肝外递送平台与管线方面取得了令人振奋的阶段性成果，并在动物实验中实现了实质性进展。我们很高兴此次能和蔚程医药携手同行，支持公司完成前沿方向的种子轮融资，非常期待公司未来发展成为这个领域的引领者，推动生命科学产业的发展和进步。” 启明创投合伙人、医疗健康行业共同负责人陈侃博士表示：“我们非常高兴能够参与并支持蔚程医药的种子轮融资。公司团队在小核酸肝外靶向递送技术领域所取得的进展，令人印象深刻。该平台技术蕴含着巨大的潜力，有望为众多目前缺乏有效治疗手段的肝外组织疾病解锁全新的治疗机会。我们高度认可周科明博士及其团队卓越的执行力与持续的创新能力，将全力支持蔚程医药，加速其创新疗法的临床转化，最终让这些突破性成果能够惠及全球更广泛的、亟待新治疗方案的患者群体。” 关于蔚程医药蔚程医药基于自主研发的肝外递送技术平台，主攻小核酸药物在非肝组织的靶向递送，旨在突破传统小核酸药物局限于肝内递送的技术瓶颈。核心使命是通过创新技术突破小核酸药物在肝外组织的递送，满足未尽的医疗需求。关于杏泽资本上海杏泽投资管理有限公司（“杏泽资本”）成立于2015年，由全球20多位富有医疗健康领域投资经验的专业人士及顾问组成，取“杏泽”之名，意在通过股权投资，借资本之力整合大健康产业资源，促行业发展，以福泽人类。目前旗下管理6支人民币基金，管理资产总额近65亿元。成立至今，杏泽资本专注于投资生命科学行业中早期和成长期的优秀企业，投资领域专注于创新生物医药、医疗器械（包括高端生命科学仪器）和创新服务产业链。已投资公司包括君实生物（1877.HK、688180.SH）、康方生物（9926.HK）、中国抗体（3681.HK）、荣昌生物（688331.SH、9995.HK）、心通医疗（2160.HK）、微创电生理（688351.SH）、Ambrx(NYSE:AMAM)、信诺维医药、六合宁远、宜联生物、齐禾生科、舶望制药、劲方医药、天泽云泰、亦诺微、拓创生物、申淇医疗、生生物流、医药魔方等70余家高速成长的明星企业。关于启明创投启明创投成立于2006年。目前，启明创投旗下管理11只美元基金，7只人民币基金，已募管理资产总额达到95亿美元。自成立至今，专注于投资科技（Technology）、医疗创新（Healthcare）等行业早期和成长期的优秀企业。截至目前，启明创投已投资超过580家高速成长的创新企业，其中有超过210家分别在美国纽交所、纳斯达克，香港交易所，上交所及深交所等交易所上市，或通过并购等方式退出，有80多家企业成为行业公认的独角兽或超级独角兽企业。启明创投投资企业中，很多已经成长为各自领域中最具影响力的公司，包括小米集团（01810.HK）、美团（03690.HK）、哔哩哔哩（NASDAQ:BILI, 09626.HK）、知乎（NYSE:ZH, 02390.HK）、石头科技（688169.SH）、优必选（09880.HK）、文远知行（NASDAQ:WRD）、影石创新（688775.SH）、甘李药业（603087.SH）、泰格医药（300347.SZ, 03347.HK）、再鼎医药（NASDAQ:ZLAB, 09688.HK）、康希诺生物（688185.SH, 06185.HK）、Schrödinger（NASDAQ:SDGR）、惠泰医疗（688617.SH）、三友医疗（688085.SH）、艾德生物（300685.SZ）、贝瑞基因（000710.SZ）、神州细胞（688520.SH）、圆心科技、英矽智能、宜联生物、礼新医药、智谱AI、阶跃星辰、壁仞科技等。如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。文中如果涉及企业信息和数据，均由受访者向分析师提供并确认。动脉网，未来医疗服务平台

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