PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced topline results from the pivotal Phase 3 PALISADE study of investigational plozasiran in patients with genetically confirmed or clinically diagnosed familial chylomicronemia syndrome (FCS), a severe genetic disease with significant unmet need and no FDA approved therapies.

加利福尼亚州帕萨迪纳市（商业新闻短讯）--箭头制药公司（NASDAQ:ARWR）今天宣布了对经基因证实或临床诊断的家族性乳糜微粒血症综合征（FCS）患者进行研究的关键性3期PALISADE研究的结果，FCS是一种严重的遗传疾病，其需求尚未得到满足，也没有FDA批准的治疗方法。

PALISADE successfully met the primary endpoint of lowering triglycerides and met all key secondary endpoints, including reducing the incidence of acute pancreatitis compared to placebo..

PALISADE成功地达到了降低甘油三酯的主要终点，并达到了所有关键的次要终点，包括与安慰剂相比降低了急性胰腺炎的发病率。。

“The strong results from the Phase 3 PALISADE study, evaluating plozasiran in patients with FCS, significantly build upon the promising results from the Phase 2 SHASTA-2 and MUIR studies in patients with severe hypertriglyceridemia and mixed hyperlipidemia, recently published in JAMA Cardiology and the New England Journal of Medicine.

“第三阶段PALISADE研究（评估FCS患者的普洛扎西兰）的有力结果，显着建立在最近发表在JAMA心脏病学和新英格兰医学杂志上的严重高甘油三酯血症和混合性高脂血症患者的第二阶段SHASTA-2和MUIR研究的有希望的结果的基础上。

These findings highlight the potential of plozasiran as a promising therapy for patients with various cardiometabolic disorders,” said Bruce Given, M.D., chief medical scientist at Arrowhead. “We look forward to discussing results at our June 25th Cardiometabolic event as part of our 2024 Summer Series of R&D Webinars and presenting the full PALISADE data at upcoming medical conferences.”.

这些发现突显了普洛扎西兰作为各种心脏代谢紊乱患者的有前途的治疗方法的潜力，”箭头首席医学科学家布鲁斯·吉文（BruceGiven）医学博士说。“我们期待着在6月25日的心脏代谢活动上讨论结果，作为2024年夏季系列研发网络研讨会的一部分，并在即将举行的医学会议上展示PALISADE的完整数据。”。

The primary endpoint for the PALISADE study was placebo adjusted median change in triglycerides at Month 10. At that timepoint, patients treated with quarterly doses of 25 and 50 mg plozasiran achieved median triglyceride reductions of -80% and -78%, respectively, with a maximal reduction of -98%. At month 12, patients treated with 25 and 50 mg plozasiran achieved median triglyceride reductions of -78% and -73%, respectively, with a maximal reduction of -99%.

PALISADE研究的主要终点是安慰剂调整后第10个月甘油三酯的中位变化。在那个时间点，接受季度剂量25和50毫克普洛扎西兰治疗的患者的甘油三酯中位数分别降低了-80%和-78%，最大降低了-98%。在第12个月，接受25和50 mg普洛扎西兰治疗的患者的甘油三酯中位数分别降低了-78%和-73%，最大降低了-99%。

These compared with median triglyceride reductions in placebo-treated patients of -17% at month 10 (primary endpoint, p<0.001) and -7% at month 12. Mean reductions in Apolipoprotein C-III (APOC3) at month 10 were -88% and -94% at 25 and 50 mg plozasiran, respectively..

这些与安慰剂治疗患者的甘油三酯中位数降低相比，在第10个月时为-17%（主要终点，p＜0.001），在第12个月时为-7%。在第10个月，载脂蛋白C-III（APOC3）的平均降低分别为25和50 mg普洛扎西兰时的-88%和-94%。。

In addition to meeting the primary endpoint, plozasiran met all key secondary endpoints and demonstrated statistical significance versus placebo.

除了达到主要终点外，普洛扎西兰还达到了所有关键的次要终点，并且与安慰剂相比具有统计学意义。

There were 4 multiplicity-controlled key secondary endpoints: 1) percent change from baseline at Months 10 and 12 (averaged) in fasting triglycerides; 2) percent change from baseline at Month 10 in fasting APOC3; 3) percent change from baseline at Month 12 in fasting APOC3; 4) incidence of positively adjudicated events of acute pancreatitis during the randomized period..

有4个多重控制的关键次要终点：1）空腹甘油三酯在第10个月和第12个月（平均）与基线的变化百分比；2） 空腹APOC3在第10个月时与基线的百分比变化；3） 空腹APOC3在第12个月时与基线的百分比变化；4） 随机期间急性胰腺炎积极判定事件的发生率。。

Plozasiran demonstrated a favorable safety profile in the PALISADE study. The number of subjects reporting treatment emergent adverse events (AEs) were similar in plozasiran and placebo groups. Severe and serious AEs were less common with plozasiran than with placebo. The most common AEs reported were abdominal pain, COVID-19, nasopharyngitis, headache and nausea..

Plozasiran在PALISADE研究中表现出良好的安全性。plozasiran组和安慰剂组报告治疗紧急不良事件（AE）的受试者人数相似。与安慰剂相比，普洛扎西兰的严重和严重AE较少见。报告的最常见不良事件是腹痛，新型冠状病毒肺炎，鼻咽炎，头痛和恶心。。

Christopher Anzalone, Ph.D., president and CEO at Arrowhead, added, “We see plozasiran data as best in class and with the potential to address multiple cardiometabolic diseases with substantial unmet need. We will now communicate the results to the FDA and discuss filing a New Drug Application for FCS.

Arrowhead总裁兼首席执行官Christopher Anzalone博士补充道：“我们认为plozasiran数据是同类中最好的，有可能解决多种心脏代谢疾病，但需求尚未得到满足。我们现在将把结果传达给FDA，并讨论为FCS提交新药申请。

We will also continue to advance multiple additional Phase 3 studies for other patient populations. It is gratifying to see one of our investigational RNAi-based medicines get potentially closer to the patients who need it most. This moment represents validation of all the hard work from so many talented Arrowhead employees, our collaborators, and the FCS community over the years.

我们还将继续为其他患者群体推进多项额外的3期研究。令人欣慰的是，我们的一种基于RNAi的研究药物可能更接近最需要它的患者。这一刻验证了多年来众多才华横溢的箭头员工、我们的合作者和FCS社区所做的所有辛勤工作。

We would like to express our sincere gratitude to the patients, caregivers, investigators, and study teams involved in the PALISADE study.”.

我们衷心感谢参与PALISADE研究的患者，护理人员，研究人员和研究团队。”。

Arrowhead plans to highlight recent data for its cardiometabolic pipeline at its June 25, 2024, Cardiometabolic event as part of the 2024 Summer Series of R&D Webinars. The company also plans to present full results from the Phase 3 PALISADE study at upcoming medical congresses and will begin to engage with global regulatory authorities about these data..

作为2024年夏季系列研发网络研讨会的一部分，箭头计划在2024年6月25日的心脏代谢活动上重点介绍其心脏代谢管道的最新数据。该公司还计划在即将举行的医学大会上提交第三阶段PALISADE研究的全部结果，并将开始与全球监管机构就这些数据进行沟通。。

About PALISADE Phase 3 Study

关于PALISADE 3期研究

The PALISADE study (NCT05089084) is a Phase 3 placebo controlled study to evaluate the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint of the study is percent change from baseline in fasting TG versus placebo at Month 10. A total of 75 subjects distributed across 39 different sites in 18 countries were randomized to receive 25 mg plozasiran, 50 mg plozasiran, or matching placebo once every three months.

PALISADE研究（NCT05089084）是一项3期安慰剂对照研究，旨在评估普洛扎西兰在遗传证实或临床诊断为FCS的成年人中的疗效和安全性。该研究的主要终点是第10个月空腹TG与安慰剂的基线变化百分比。分布在18个国家39个不同地点的75名受试者被随机分配，每三个月接受一次25毫克普洛扎西兰，50毫克普洛扎西兰或匹配的安慰剂。

Participants who completed the randomized period were eligible to continue in a 2-part extension period, where all participants receive plozasiran..

完成随机期的参与者有资格继续分为两部分的延长期，所有参与者都接受普洛扎西兰治疗。。

About Familial Chylomicronemia Syndrome

关于家族性乳糜微粒血症综合征

Familial chylomicronemia syndrome (FCS) is a severe and ultrarare genetic disease often caused by various monogenic mutations. FCS leads to extremely high triglyceride (TG) levels, typically over 880 mg/dL. Such severe elevations can lead to various serious signs and symptoms including acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues.

家族性乳糜微粒血症综合征（FCS）是一种严重且超罕见的遗传疾病，通常由各种单基因突变引起。FCS导致甘油三酯（TG）水平极高，通常超过880 mg/dL。这种严重的升高可能导致各种严重的体征和症状，包括急性和潜在致命的胰腺炎，慢性腹痛，糖尿病，肝脂肪变性和认知问题。

Currently, the therapeutic options that can adequately treat FCS are limited..

目前，可以充分治疗FC的治疗选择是有限的。。

About Plozasiran

FreeBSD吉祥物

Plozasiran, previously called ARO-APOC3, is a first-in-class investigational RNA interference (RNAi) therapeutic designed to reduce production of Apolipoprotein C-III (APOC3) which is a component of triglyceride rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 increases triglyceride levels in the blood by inhibiting breakdown of TRLs by lipoprotein lipase and uptake of TRL remnants by hepatic receptors in the liver.

Plozasiran，以前称为ARO-APOC3，是一种一流的研究性RNA干扰（RNAi）治疗剂，旨在减少载脂蛋白C-III（APOC3）的产生，载脂蛋白C-III是富含甘油三酯的脂蛋白（TRL）的组成部分，也是甘油三酯代谢的关键调节剂。APOC3通过抑制脂蛋白脂肪酶对TRL的分解和肝脏受体对TRL残留物的摄取来增加血液中的甘油三酯水平。

The goal of treatment with plozasiran is to reduce the level of APOC3, thereby reducing triglycerides and restoring lipids to more normal levels..

普洛扎西兰治疗的目标是降低APOC3的水平，从而降低甘油三酯并将脂质恢复到更正常的水平。。

In multiple clinical studies, investigational plozasiran demonstrated reductions in triglycerides and multiple atherogenic lipoproteins in patients with familial chylomicronemia syndrome (FCS), severe hypertriglyceridemia (SHTG), and mixed hyperlipidemia. Plozasiran has demonstrated a favorable safety profile to date with treatment emergent adverse events reported that reflect the comorbidities and underlying conditions of the study populations.

在多项临床研究中，研究性普洛扎西兰显示家族性乳糜微粒血症综合征（FCS），严重高甘油三酯血症（SHTG）和混合性高脂血症患者的甘油三酯和多种致动脉粥样硬化脂蛋白降低。迄今为止，Plozasiran已显示出良好的安全性，报告的治疗紧急不良事件反映了研究人群的合并症和潜在状况。

Plozasiran is currently being investigated in the PALISADE Phase 3 clinical study in patients with FCS, which recently completed, and the Phase 3 SHASTA-3 and SHASTA-4 studies in patients with SHTG..

Plozasiran目前正在最近完成的针对FCS患者的PALISADE 3期临床研究以及针对SHTG患者的3期SHASTA-3和SHASTA-4研究中进行研究。。

Plozasiran has been granted Orphan Drug Designation and Fast Track Designation by the U.S. Food and Drug Administration and Orphan Drug Designation by the European Medicines Agency.

Plozasiran已被美国食品和药物管理局授予孤儿药指定和快速通道指定，并被欧洲药品管理局授予孤儿药指定。

About Plozasiran EAP

关于Plozasiran EAP

Arrowhead is committed to bringing new investigational medicines to patients with serious diseases as quickly and efficiently as possible. The company has established an early access program (EAP) for some individuals living with FCS. As with any investigational medicine that has not been approved by regulatory authorities, investigational plozasiran may or may not be effective in treating your diagnosis or condition, and there may be risks associated with its use.

Arrowhead致力于尽快有效地为患有严重疾病的患者提供新的研究药物。该公司为一些生活在FCS中的个人建立了早期访问计划（EAP）。与未经监管机构批准的任何研究药物一样，研究性普洛扎西兰可能对治疗您的诊断或病情有效，也可能无效，并且可能存在与其使用相关的风险。

If you are a patient or caregiver wishing to know more about this plozasiran EAP for FCS, please discuss this EAP and all treatment options with your treating physician. If you are a treating physician and are seeking information about the plozasiran EAP or would like to request access for a patient, please contact EAP@arrowheadpharma.com..

如果您是一名患者或护理人员，希望了解更多有关FCS的plozasiran EAP的信息，请与您的主治医师讨论此EAP和所有治疗方案。如果您是一名主治医师，正在寻求有关plozasiran EAP的信息，或者希望请求患者访问，请联系EAP@arrowheadpharma.com..

About Arrowhead Pharmaceuticals

关于箭头制药

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.

箭头制药公司通过沉默导致顽固性疾病的基因来开发治疗顽固性疾病的药物。使用广泛的RNA化学组合和有效的递送方式，箭头疗法触发RNA干扰机制，以诱导靶基因的快速，深入和持久的敲低。

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..

RNA干扰或RNAi是活细胞中存在的一种机制，可抑制特定基因的表达，从而影响特定蛋白质的产生。Arrowhead基于RNAi的疗法利用了这种基因沉默的自然途径。。

For more information, please visit www.arrowheadpharma.com, or follow us on X (formerly Twitter) at @ArrowheadPharma or on LinkedIn. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts.

有关更多信息，请访问www.arrowheadharma.com，或通过X（以前的推特）关注我们@arrowheadharma或LinkedIn。要添加到公司的电子邮件列表并直接接收新闻，请访问http://ir.arrowheadpharma.com/email-alerts.

Safe Harbor Statement under the Private Securities Litigation Reform Act:

私人证券诉讼改革法案下的安全港声明：

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.

本新闻稿包含1995年《私人证券诉讼改革法案》中“安全港”条款所指的前瞻性声明。除历史信息外，本版本中包含的任何声明都可能被视为前瞻性声明。在不限制上述一般性的情况下，诸如“可能”、“将”、“预期”、“相信”、“预期”、“希望”、“打算”、“计划”、“项目”、“可能”、“估计”、“继续”、“目标”、“预测”或“继续”等词语或其其他变体或类似术语的否定词旨在识别此类前瞻性陈述。

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.

此外，任何涉及我们未来财务业绩预测、业务趋势、对我们产品线或候选产品的期望（包括预期的监管提交和临床计划结果）、我们与其他公司合作的前景或益处，或未来事件或情况的其他特征的声明都是前瞻性声明。

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, 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; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties.

这些前瞻性陈述包括但不限于关于我们的临床前研究和临床试验以及我们的研究和开发计划的开始，时间，进展和结果的陈述；我们对合作伙伴关系、许可和/或合作安排以及我们已经达成或将来可能达成的其他战略安排和交易的潜在利益的期望；我们对里程碑、特许权使用费或现有协议下可能应付给第三方或来自第三方的其他付款的信念和期望；以及我们对未来收入、研发费用、资本要求和向第三方付款的估计。

These statements are based u.

这些声明基于美国。

Source: Arrowhead Pharmaceuticals, Inc.

来源：Arrowhead Pharmaceuticals，Inc。