Olpasiran

关注并星标CPHI制药在线 *展会预登记火热进行中，👆扫描二维码免费领票！ 心血管疾病是全球健康的“头号威胁”之一。高胆固醇（例如低密度脂蛋白胆固醇LDL-C）是诱发动脉粥样硬化的重要因素。传统治疗中，他汀类药物需每日服用，患者因依从性差难以达标。  2025年7月31日，诺华宣布其siRNA（小干扰RNA）疗法inclisiran（商品名：Leqvio®）获FDA批准为一线单药，每年仅需注射两次即可降低成人高胆固醇血症患者的LDL-C水平。 一、Leqvio的突破性 Leqvio是一款“first-in-class”、靶向PCSK9 mRNA的siRNA疗法。2021年首次获批时，ORION系列试验（ORION-9、-10、-11）显示，Leqvio较安慰剂持续降低LDL-C达52%，参与试验的3400余名动脉粥样硬化性心血管疾病（ASCVD）或杂合子家族性高胆固醇（HeFH）患者的数据夯实了其疗效。2023年适应症扩展后，其可作为饮食和他汀类药物治疗的辅助用药。 今年7月的这次适应症扩展，是FDA主动要求更新Leqvio药品标签，更新后的药品标签去除了Leqvio必须与他汀类药物联合使用或在其基础上使用的限制。同样，本次适应症拓展也源于扎实的临床数据。 2024年公布的V-MONO三期研究数据更具说服力：对未接受降脂治疗的低或中风险ASCVD患者，Leqvio单药疗效优于安慰剂和依折麦布（ezetimibe），LDL-C降低幅度具有临床和统计学意义。这为其成为单药疗法提供了关键依据。  此外，“半年一针”的给药方式是Leqvio的核心优势。不同于每日服药，Leqvio由医护人员注射，初始两针间隔3个月，此后每6个月一次。这一给药频率直击传统治疗痛点，美国高达80%的ASCVD患者难以达到指南推荐的LDL-C<70 mg/dL的目标，而长效给药大幅提升了用药依从性。 本次批准中，其他更新内容还包括将标签中“原发性高脂血症”一词统一修改为更具体的“高胆固醇血症”，更精准聚焦LDL-C降低，强化了其作为精准降脂疗法的定位，为临床应用提供了清晰指引。  二、siRNA技术是长效特性的科学根基 Leqvio的成功，源于siRNA技术的独特优势，它通过靶向PCSK9基因的mRNA，从源头抑制该蛋白合成。PCSK9蛋白会对低密度脂蛋白（LDL）受体的回收与再利用产生抑制作用。所以，若能降低PCSK9蛋白的水平，就可使更多LDL受体重新回到肝细胞表面。这些受体能结合更多的LDL，并将其从血液中清除出去。  技术迭代是长效的根基。早期siRNA因递送系统缺陷难以成药，而Leqvio采用了三触角结构N-乙酰半乳糖（GalNAc）偶联技术，GalNAc配体可以精准的与肝细胞膜表面表达的ASGPR结合。 图注：Leqvio的结构（来源：参考资料[4]） 由于Leqvio抑制PCSK9蛋白的产生是持续性的，而且肝脏清除LDL-C的能力增强，因此这种降LDL-C的效果可以持续较长时间。这使其无需频繁给药，就能持续降脂，解决了慢性病治疗的“依从性魔咒”。 图注：Leqvio在体内的作用机制（来源：参考资料[4]） 众多药企也布局了siRNA技术。礼来的Lepodisiran在二期ALPACA试验中实现Lp(a)水平平均降低93.9%，一些患者的降低持续了近1.5年[5]。安进的Olpasiran能将Lp(a)降低95%以上，并且在最后一剂后近一年对Lp(a)的降低显示出持久的效果[]。这些临床数据印证了siRNA在降脂领域的巨大潜力，不仅仅是PCSK9，更多靶点正被攻克。 中国药企也在加速追赶。齐鲁制药、石药集团等企业的长效siRNA制剂进入临床，靶点覆盖PCSK9、ANGPTL3等。舶望制药与诺华达成超41亿美元合作，其siRNA药物管线进展迅速。瑞博生物的RBD7022靶向ASGPR/PCSK9，腾盛博药的elebsiran聚焦乙肝，维亚臻生物的VSA006靶向17β-HSD13瞄准代谢相关脂肪性肝炎（MASH），展现出本土创新潜力。 结语 从每日服药到半年一针，从辅助治疗到一线单药，Leqvio的获批是siRNA技术成熟的代表。它证明了RNA干扰不仅能攻克罕见病，更能在心血管等慢性病领域掀起变革。随着更多临床试验的推进，以及更多企业的技术突破，一次给药管半年甚至一年的降脂时代已近在眼前。 siRNA的高度特异性、广靶点潜力和长效特性，将为更多疾病提供新疗法。未来，siRNA疗法有望为全球患者带来更轻松、更有效的健康守护。  参考资料： 1.Novartis twice-yearly* Leqvio® (inclisiran) receives FDA approval for new indication enabling first-line use, Jul 31, 2025, www.novartis.com 2.FDA Approves Inclisiran (Leqvio) Label Update as First-Line Monotherapy in Hypercholesterolemia, July 31, 2025, www.hcplive.com 3.Novartis twice-yearly* Leqvio® demonstrated clinically meaningful, statistically significant LDL-C lowering as a monotherapy in patients at low or moderate ASCVD risk, Aug 28, 2024, www.novartis.com 4.Migliorati, Julia M et al. “siRNA drug Leqvio (inclisiran) to lower cholesterol.” Trends in pharmacological sciences vol. 43,5 (2022): 455-456. doi:10.1016/j.tips.2022.02.003 5.Lilly's lepodisiran reduced levels of genetically inherited heart disease risk factor, lipoprotein(a), by nearly 94% from baseline at the highest tested dose in adults with elevated levels, March 30, 2025, investor.lilly.com 6.AMGEN PRESENTS LATE-BREAKING PHASE 2 OLPASIRAN DATA AT ESC 2023, www.amgen.com END 智药研习社近期直播预告 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~

Arrowhead Pharmaceuticals Reports... – Conference Call and Webcast Today, August 7, 2025, at 4:30 p.m. ET PASADENA, Calif.–(BUSINESS WIRE)–Aug. 7, 2025– Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced financial results for its fiscal 2025 third quarter ended June 30, 2025. The Company is hosting a conference call today, August 7, 2025, at 4:30 p.m. ET to discuss the results. “Arrowhead continues to achieve strong execution in discovery, clinical and regulatory, and business development. Our pipeline has become quite mature, with four Arrowhead discovered candidates currently in pivotal Phase 3 studies. In addition, our commercial buildout is designed to make us launch ready on day one, should plozasiran receive regulatory approval on the November 18, 2025, PDUFA date,” said Christopher Anzalone, Ph.D., President and CEO at Arrowhead. “We continue to maintain a strong balance sheet, which we believe gives us the financial resources to move multiple innovative new medicines through the clinical and regulatory process and ultimately get them to the patients who need them.” Selected Recent Events Announced the signing of an asset purchase agreement between Sanofi and Visirna Therapeutics, a majority-owned subsidiary of Arrowhead created to develop and commercialize four of Arrowhead’s investigational cardiometabolic candidates in Greater China. Summary terms of the agreement include: Visirna will receive an upfront payment of $130 million from Sanofi. In addition, Visirna will be eligible to receive further milestone payments of up to $265 million upon approval of plozasiran across various indications in mainland China. Sanofi will receive an exclusive license to develop and commercialize investigational plozasiran in Greater China from Visirna Therapeutics, offering potential treatment to people living with elevated triglycerides. Earned a $100 million milestone payment from Sarepta Therapeutics when Arrowhead reached the first of two prespecified enrollment targets and subsequent authorization to dose escalate in a Phase 1/2 clinical study of ARO-DM1, an investigational RNA interference (RNAi) therapeutic for the treatment of type 1 myotonic dystrophy (DM1), the most common adult-onset muscular dystrophy. Arrowhead currently expects to achieve the second enrollment target by the end of 2025, which would trigger an additional $200 million milestone payment from Sarepta. Completed enrollment in investigational plozasiran clinical studies SHASTA-3, SHASTA-4, and MUIR-3, the company’s global Phase 3 clinical studies designed to support regulatory submissions for marketing approval in the treatment of severe hypertriglyceridemia. Arrowhead anticipates completing the primary portion of these studies in mid-2026 with topline data expected shortly thereafter and planned submissions for regulatory review and potential approval to follow. The company previously submitted a New Drug Application (NDA) for plozasiran based on positive Phase 3 PALISADE study results in patients with familial chylomicronemia syndrome, which the U.S. FDA has accepted with a Prescription Drug User Fee Act (PDUFA) action date set for November 18, 2025. Dosed the first subject in the YOSEMITE Phase 3 clinical trial of zodasiran, the company’s investigational RNAi therapeutic being developed as a potential treatment for homozygous familial hypercholesterolemia (HoFH), a rare genetic condition that leads to severely elevated LDL-cholesterol and early onset cardiovascular disease. Zodasiran is the fourth investigational RNAi-based candidate developed by Arrowhead to reach late-stage pivotal studies, after investigational drugs plozasiran, fazirsiran (licensed to Takeda) and olpasiran (licensed to Amgen). Dosed the first subjects in a Phase 1/2a clinical trial of ARO-ALK7, the company’s investigational RNAi therapeutic being developed as a potential treatment for obesity. ARO-ALK7 is designed to intervene in a known pathway that signals the body to store fat in adipose tissue with a novel mechanism of action that may better preserve lean muscle mass compared to currently approved obesity therapies. The study initiates in otherwise healthy obese subjects using single and multiple escalating doses of ARO-ALK7 monotherapy and is expected to progress rapidly to investigate combinations of ARO-ALK7 with tirzepatide in obese patients with and without type 2 diabetes. Visirna will receive an upfront payment of $130 million from Sanofi. In addition, Visirna will be eligible to receive further milestone payments of up to $265 million upon approval of plozasiran across various indications in mainland China. Sanofi will receive an exclusive license to develop and commercialize investigational plozasiran in Greater China from Visirna Therapeutics, offering potential treatment to people living with elevated triglycerides. Selected Fiscal 2025 Third Quarter Financial Results ARROWHEAD PHARMACEUTICALS, INC. CONSOLIDATED CONDENSED FINANCIAL INFORMATION (in thousands, except per share amounts) Three Months Ended June 30, OPERATING SUMMARY 2025 2024 (Unaudited) Revenue $ 27,767 $ — Operating Expenses: Research and development 162,368 152,431 General and administrative expenses 30,949 23,710 Total operating expenses 193,317 176,141 Operating loss (165,550 ) (176,141 ) Total other (expense) income (13,539 ) 2,164 Loss before income tax expense and noncontrolling interest (179,089 ) (173,977 ) Income tax (benefit) expense (437 ) — Net loss including noncontrolling interest (178,652 ) (173,977 ) Net loss attributable to noncontrolling interest, net of tax (3,411 ) (3,184 ) Net loss attributable to Arrowhead Pharmaceuticals, Inc. $ (175,241 ) $ (170,793 ) Net loss per share attributable to Arrowhead Pharmaceuticals, Inc. – Diluted $ (1.26 ) $ (1.38 ) Weighted-average shares used in calculating – Diluted 139,039 124,199 FINANCIAL POSITION SUMMARY June 30, 2025 September 30, 2024 (unaudited) Cash, cash equivalents and restricted cash $ 129,793 $ 102,685 Available-for-sale securities, at fair value 770,579 578,276 Total cash resources (Cash, cash equivalents and restricted cash and Available-for-sale securities, at fair value) 900,372 680,961 Other current and long-term assets 480,240 458,841 Total Assets $ 1,380,612 $ 1,139,802 Liability related to the sale of future royalties $ 360,254 $ 341,361 Credit Facility 240,332 393,183 Deferred revenue 22,979 — Other liabilities 237,241 214,195 Total Liabilities $ 860,806 $ 948,739 Total Arrowhead Pharmaceuticals, Inc. Stockholders’ Equity 522,313 185,444 Noncontrolling Interest (2,507 ) 5,619 Total Noncontrolling Interest and Stockholders’ Equity $ 519,806 $ 191,063 Total Liabilities, Noncontrolling Interest and Stockholders’ Equity $ 1,380,612 $ 1,139,802 Shares Outstanding 138,144 124,376 Webcast and Conference Call and Details Investors may access a live audio webcast on the Events and Presentations page under the Investors section of the Arrowhead website. A replay of the webcast will be available approximately two hours after the conclusion of the call. For analysts that wish to participate in the conference call, please register at https://register-conf.media-server.com/register/BI3955ca6732974874b0bc0ac323811a7f. Once registered, you will receive the dial-in number and a personalized PIN code that will be required to access the call. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit www.arrowheadpharma.com, or follow us on X (formerly Twitter) at @ArrowheadPharma, LinkedIn, Facebook, and Instagram. To be added to the Company’s email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts. Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, including the timing of achievement of the next ARO-DM1 milestone, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements, including our ability to achieve such milestones on projected timelines (if at all) and receive timely payment if milestones are achieved; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We disclaim any intention to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc. View source version on businesswire.com: https://www.businesswire.com/news/home/20250807601354/en/ Arrowhead Pharmaceuticals, Inc. Vince Anzalone, CFA 626-304-3400 ir@arrowheadpharma.com Investors: LifeSci Advisors, LLC Brian Ritchie 212-915-2578 britchie@lifesciadvisors.com Media: LifeSci Communications, LLC Kendy Guarinoni, Ph.D. 724-910-9389 kguarinoni@lifescicomms.com Source: Arrowhead Pharmaceuticals, Inc.