CAMBRIDGE, Mass.--(BUSINESS WIRE)--Oct. 9, 2024--

马萨诸塞州剑桥市--（商业新闻短讯）--2024年10月9日--

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced the submission of its supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM).

领先的RNAi治疗公司Alnylam Pharmaceuticals，Inc.（纳斯达克：ALNY）今天宣布向美国食品和药物管理局（FDA）提交vutrisiran的补充新药申请（sNDA），vutrisiran是一种正在开发的用于治疗ATTR淀粉样变性伴心肌病（ATTR-CM）的研究性RNAi治疗剂。

Vutrisiran is the generic name for AMVUTTRA®, which is currently approved by the U.S. FDA for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults. As part of the submission, the Company utilized a Priority Review Voucher, which obligates the FDA to an accelerated review timeline. .

Vutrisiran是AMVUTTRA®的通用名称，目前已被美国FDA批准用于治疗成人遗传性ATTR淀粉样变性的多发性神经病。作为提交文件的一部分，该公司使用了优先审查凭证，这使FDA有义务加快审查时间表。。。

“We are proud that with this first regulatory submission, we are a significant step closer to bringing vutrisiran to patients with ATTR amyloidosis with cardiomyopathy, which is a steadily progressive, debilitating, and ultimately fatal disease. HELIOS-B demonstrated rapid knockdown of TTR with vutrisiran and an improvement in death and cardiovascular events, as well as delays in disease progression, with vutrisiran as compared to placebo, with consistent effects across all pre-specified subgroups,” said Pushkal Garg, M.D., Chief Medical Officer, Alnylam.

Alnylam首席医疗官Pushkal Garg医学博士说：“我们很自豪，通过首次提交监管文件，我们离将vutrisiran带给患有心肌病的ATTR淀粉样变性患者又近了一大步，这是一种稳步进展，使人衰弱并最终致命的疾病。HELIOS-B证明了vutrisiran的TTR快速敲低，与安慰剂相比，vutrisiran的死亡和心血管事件以及疾病进展延迟有所改善，在所有预先指定的亚组中都具有一致的效果。”。

“We believe that, pending regulatory approval, vutrisiran has the potential to become a first-line therapy for ATTR amyloidosis with cardiomyopathy. We look forward to working with the FDA over the coming months on this application to bring this medicine to patients as rapidly as possible. Additional filings in other geographies are underway.” .

“我们相信，在监管部门批准之前，vutrisiran有可能成为ATTR淀粉样变性伴心肌病的一线治疗药物。我们期待着在未来几个月内与FDA合作，尽快将这种药物带给患者。其他地区的其他申请正在进行中。”。。

The application to the FDA was based on positive results from HELIOS-B, a Phase 3, randomized, double-blind, placebo-controlled multicenter global study in patients with ATTR-CM with substantial background use of other effective therapies. 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.

FDA的申请是基于HELIOS-B的阳性结果，HELIOS-B是一项针对ATTR-CM患者的3期随机，双盲，安慰剂对照多中心全球研究，大量背景使用其他有效疗法。该研究表明，vutrisiran对ATTR-CM患者的死亡和心血管事件结果，功能能力和生活质量有良好的影响。

The safety profile of vutrisiran in HELIOS-B was consistent with the established profile of the drug. In HELIOS-B, rates of adverse events (AEs), serious AEs, severe AEs, and AEs leading to study drug discontinuation were similar between the vutrisiran and placebo arms. .

vutrisiran在HELIOS-B中的安全性与该药物的既定特征一致。在HELIOS-B中，vutrisiran组和安慰剂组的不良事件（AE），严重AE，严重AE和导致研究药物停药的AE发生率相似。。。

Today, the Company will host its TTR Investor Day starting at 8:30 am ET in New York City. The event will feature presentations from the Company’s management team, including senior leaders from the commercial organization who will discuss launch preparation and highlight the potential for market leadership in ATTR-CM.

今天，该公司将于美国东部时间上午8:30在纽约市举办TTR投资者日。此次活动将展示公司管理团队的演讲，其中包括商业组织的高级领导，他们将讨论发布准备工作，并强调ATTR-CM的市场领导潜力。

The event will be webcast on the Investors section of the Company’s website, www.alnylam.com. A replay will be available on the Alnylam website within 48 hours after the event. .

活动将在公司网站www.alnylam.com的投资者部分进行网络直播。活动结束后48小时内，将在alnylam网站上进行重播。。。

HELIOS-B Study Design

HELIOS-B研究设计

HELIOS-B (NCT: NCT04153149) was a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed and powered to evaluate the efficacy and safety of vutrisiran on the reduction of all-cause mortality and recurrent cardiovascular events as a primary composite endpoint in patients with ATTR amyloidosis with cardiomyopathy.

HELIOS-B（NCT:NCT04153149）是一项3期随机，双盲，安慰剂对照的多中心全球研究，旨在评估vutrisiran在降低全因死亡率和复发性心血管事件方面的疗效和安全性，作为ATTR淀粉样变性伴心肌病患者的主要复合终点。

The study randomized 655 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy. Patients were randomized 1:1 to receive vutrisiran 25mg or placebo subcutaneously once every three months during a double-blind treatment period of up to 36 months. After the double-blind period, all eligible patients remaining on the study to were able receive vutrisiran in an open-label extension period of HELIOS-B. .

该研究将655名成人ATTR淀粉样变性（遗传性或野生型）心肌病患者随机分组。在长达36个月的双盲治疗期间，患者以1:1的比例随机接受vutrisiran 25mg或安慰剂，每三个月皮下注射一次。在双盲期后，所有仍在研究中的符合条件的患者都能够在HELIOS-B的开放标签延长期内接受vutrisiran。。。

AMVUTTRA® (vutrisiran) U.S. Indication and Important Safety Information

AMVUTTRA®（vutrisiran）美国指示和重要安全信息

Indication

指示

AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

AMVUTTRA适用于治疗成人遗传性甲状腺素转运蛋白介导的淀粉样变性的多发性神经病。

Important Safety Information

重要安全信息

Reduced Serum Vitamin A Levels and Recommended Supplementation

降低血清维生素A水平并建议补充

AMVUTTRA® (vutrisiran) 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. .

AMVUTTRA®（vutrisiran）治疗导致血清维生素a水平降低。建议服用AMVUTTRA的患者以推荐的每日摄入量（RDA）补充维生素A。。。。

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).

如果患者出现提示维生素A缺乏的眼部症状（例如夜盲症），应将其转诊给眼科医生。

Adverse Reactions

不良反应

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%).

AMVUTRA治疗患者最常见的不良反应是肢体疼痛（15%），关节痛（11%），呼吸困难（7%）和维生素A下降（7%）。

For additional information about AMVUTTRA, please see the full Prescribing Information.

有关AMVUTTRA的更多信息，请参阅完整的处方信息。

About AMVUTTRA® (vutrisiran)

关于AMVUTTRA® （武特里西兰）

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.

。AMVUTTRA每季度通过皮下注射给药，已在15多个国家获得批准并上市，用于治疗成人遗传性甲状腺素转运蛋白介导的淀粉样变性（hATTR PN）的多发性神经病。

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. .

Vutrisiran还正在开发用于治疗ATTR淀粉样变性伴心肌病（ATTR-CM），该疾病包括该疾病的野生型和遗传形式。有关AMVUTTRA的更多信息，包括完整的美国处方信息，请访问AMVUTTRA.com。。。

About ATTR

关于属性

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.

运甲状腺素蛋白淀粉样变性病（ATTR）是由错误折叠的运甲状腺素蛋白（TTR）蛋白引起的一种诊断不足，快速进展，衰弱和致命的疾病，该蛋白以淀粉样蛋白沉积物的形式积聚在身体的各个部位，包括神经，心脏和胃肠道。患者可能会出现多发性神经病，心肌病或两种疾病的表现。

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.1-4.

有两种不同形式的ATTR-遗传性ATTR（hATTR），它是由TTR基因变异引起的，影响全球约50000人，和野生型ATTR（wtATTR），它在没有TTR基因变异的情况下发生，影响全球约200000-300000人。

About RNAi

关于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.5 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.6 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.

RNAi（RNA干扰）是一种基因沉默的自然细胞过程，代表了当今生物学和药物开发中最有前途和快速发展的前沿之一。它的发现被誉为“每十年左右发生一次的重大科学突破”，并获得了2006年诺贝尔生理学或医学奖的认可。6通过利用我们细胞中发生的RNAi的自然生物学过程，一类被称为RNAi疗法的新型药物现已成为现实。

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.5 This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. .

小干扰RNA（siRNA）是介导RNAi并构成Alnylam RNAi治疗平台的分子，通过有效沉默信使RNA（mRNA）（编码致病或疾病途径蛋白的遗传前体）而在当今药物的上游发挥作用，从而阻止它们的产生。5这是一种革命性的方法，有可能改变遗传和其他疾病患者的护理。。。

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.

Alnylam（纳斯达克股票代码：ALNY）领导将RNA干扰（RNAi）转化为一类全新的创新药物，有可能改变患有罕见和流行疾病且需求未得到满足的人的生活。基于诺贝尔奖获得者的科学，RNAi疗法代表了一种强大的，临床验证的方法，产生了转化药物。

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 has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” 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拥有丰富的研究药物渠道，包括处于后期开发阶段的多种候选产品。Alnylam正在实施其“Alnylam P5x25”战略，通过可持续创新和卓越的财务表现，为世界各地的罕见病和常见病患者提供变革性药物，从而产生领先的生物技术概况。

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总部位于马萨诸塞州剑桥市。有关我们的人员、科学和管道的更多信息，请访问www.Alnylam.com，并通过X（以前的Twitter）或LinkedIn、Facebook或Instagram与我们联系。。。

Alnylam Forward-Looking Statements

Alnylam前瞻性声明

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; the potential for vutrisiran to obtain regulatory approval for the treatment of ATTR amyloidosis with cardiomyopathy; the safety and efficacy of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy, the potential of vutrisiran to including its potential to become a first-line therapy and a market-leading therapy for patients with ATTR amyloidosis with cardiomyopathy,; and Alnylam’s view with respect to the timing of regulatory review potential for a reduced review timeline by the FDA and any resulting approval(s) of vutrisiran for the treatment of ATTR amyloidosis in the U.S.

本新闻稿包含《1933年证券法》第27A节和《1934年证券交易法》第21E节所指的前瞻性声明。关于Alnylam的期望、信念、目标、计划或前景的历史事实陈述以外的所有陈述，包括但不限于Alnylam对vutrisiran治疗ATTR淀粉样变性伴心肌病的安全性和有效性的期望；vutrisiran获得监管部门批准治疗ATTR淀粉样变性伴心肌病的潜力；vutrisiran治疗ATTR淀粉样变性伴心肌病的安全性和有效性，vutrisiran成为ATTR淀粉样变性伴心肌病患者的一线治疗和市场领先治疗的潜力，；以及Alnylam关于FDA缩短审查时间表的监管审查时间的观点，以及vutrisiran在美国治疗ATTR淀粉样变性的任何最终批准。

and other countries Alnylam’s global regulatory submissions for vutrisiran 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 P5x25” 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 i.

和其他国家一样，Alnylam针对vutrisiran提交的全球监管报告应被视为前瞻性声明。由于各种重要风险、不确定性和其他因素，包括但不限于与以下相关的风险和不确定性，实际结果和未来计划可能与这些前瞻性声明所示存在重大差异：Alnylam成功执行其“Alnylam P5x25”战略的能力；Alnylam成功证明其候选产品有效性和安全性的能力；Alnylam候选产品（包括vutrisiran）的临床前和临床结果；监管机构的行动或建议以及Alnylam获得i监管批准的能力。

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Alnylam Pharmaceuticals, Inc.

Alnylam Pharmaceuticals，股份有限公司。

Christine Regan Lindenboom

克里斯汀·里根·林登博姆

(Investors and Media)

（投资者和媒体）

+1-617-682-4340

+1-617-682-4340

Josh Brodsky

乔什·布罗茨基

(Investors)

（投资者）

+1-617-551-8276

+1-617-551-8276

Source: Alnylam Pharmaceuticals, Inc.

资料来源：Alnylam Pharmaceuticals，股份有限公司。