CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun. 24, 2024--

马萨诸塞州剑桥市--（商业新闻短讯）--2024年6月24日--

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced positive topline results from its HELIOS-B Phase 3 study of 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.（纳斯达克代码：ALNY）今天宣布，其对vutrisiran的HELIOS-B 3期研究取得了积极的结果，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。

The study met the primary endpoint, demonstrating a statistically significant reduction in the composite of all-cause mortality and recurrent cardiovascular (CV) events during the double-blind period in both the overall population (HR 0.718, p-value 0.0118; n=654) and in the monotherapy population (patients not receiving tafamidis at baseline; HR 0.672, p-value 0.0162; n=395). .

该研究达到了主要终点，表明总体人群（HR 0.718，p值0.0118；n=654）和单药治疗人群（基线时未接受塔法米的患者；HR 0.672，p值0.0162；n=395）在双盲期内全因死亡率和复发性心血管（CV）事件的复合物在统计学上显着降低。。。

The study also demonstrated statistically significant improvements across all secondary endpoints in both the overall and monotherapy populations. This includes key measures of disease progression: 6-minute walk test (6-MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Class at Month 30 (p<0.025 for all).

该研究还表明，在整体和单一治疗人群中，所有次要终点的统计学显着改善。这包括疾病进展的关键指标：6分钟步行测试（6-MWT），堪萨斯城心肌病问卷（KCCQ）和纽约心脏协会（NYHA）在第30个月的等级（全部p＜0.025）。

Importantly, treatment with vutrisiran also reduced all-cause mortality in the overall population (HR 0.645, p<0.025) and in the monotherapy population (HR 0.655, p<0.05) up to Month 42. This was a pre-specified, intent-to-treat analysis that included up to six months of data from the open-label extension. .

重要的是，在第42个月之前，用vutrisiran治疗也降低了总体人群（HR 0.645，p<0.025）和单药治疗人群（HR 0.655，p<0.05）的全因死亡率。这是一个预先指定的意向治疗分析，其中包括来自开放标签扩展的长达六个月的数据。。。

“I’m thrilled by these overwhelmingly positive data from the HELIOS-B study, which suggest that vutrisiran has the potential to address the needs of patients with ATTR amyloidosis with cardiomyopathy, a steadily progressive, debilitating, and ultimately fatal disease,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam.

Alnylam首席医疗官Pushkal Garg医学博士说：“我对HELIOS-B研究中这些压倒性的积极数据感到兴奋，这些数据表明，vutrisiran有潜力满足患有心肌病的ATTR淀粉样变性患者的需求，这种疾病是一种稳步进展的，衰弱的，最终致命的疾病。”。

“The results showed that vutrisiran improved cardiovascular outcomes, including survival, function and quality of life in all patient groups with ATTR cardiomyopathy. We are moving with urgency to file these compelling data with regulators to bring this medicine to patients around the world.” .

“结果显示，vutrisiran改善了所有ATTR心肌病患者的心血管结局，包括生存率、功能和生活质量。我们迫切需要将这些令人信服的数据提交给监管机构，以便将这种药物带给世界各地的患者。”。。

In addition, vutrisiran demonstrated consistent effects on the primary composite endpoint and all secondary endpoints across all key subgroups, including baseline tafamidis use, ATTR disease type and measures of disease severity.

此外，vutrisiran在所有关键亚组中对主要复合终点和所有次要终点表现出一致的影响，包括基线他法米地的使用，ATTR疾病类型和疾病严重程度的测量。

In the HELIOS-B study, vutrisiran demonstrated encouraging safety and tolerability, consistent with its established profile. Rates of adverse events (AEs), serious AEs and AEs leading to study drug discontinuation were similar between the vutrisiran and placebo arms. No AEs were seen ≥3% more frequently in the vutrisiran arm compared to the placebo arm. .

在HELIOS-B研究中，vutrisiran表现出令人鼓舞的安全性和耐受性，与其既定的概况一致。vutrisiran组和安慰剂组的不良事件（AE），严重AE和导致研究药物停药的AE发生率相似。与安慰剂组相比，vutrisiran组没有出现≥3%的AE。。。

“I am overjoyed by the results of the HELIOS-B study, which suggest the potential for vutrisiran to be a transformative medicine for patients with ATTR amyloidosis with cardiomyopathy,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. “Assuming favorable regulatory review, vutrisiran has the potential to become the new standard of care for the treatment of this disease, driving Alnylam’s next era of substantial growth.” .

Alnylam首席执行官Yvonne Greenstreet说：“我对HELIOS-B研究的结果感到欣喜若狂，这表明vutrisiran有可能成为ATTR淀粉样变性伴心肌病患者的变革药物。”。“如果监管审查顺利，vutrisiran有可能成为治疗这种疾病的新标准，推动Alnylam的下一个大幅增长时代。”。。

HELIOS-B (NCT: NCT04153149) is 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 in the overall and monotherapy populations.

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在整体和单药治疗人群中的主要复合终点。

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 may receive vutrisiran in an open-label extension period. .

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，所有符合条件的患者都可以在开放标签的延长期内接受vutrisiran治疗。。。

Detailed results from the HELIOS-B study have been submitted as a late-breaking abstract to the European Society of Cardiology for presentation. The Company plans to proceed with global regulatory submissions starting later this year, including filing a supplemental New Drug Application with the U.S.

HELIOS-B研究的详细结果已作为最新摘要提交给欧洲心脏病学会进行介绍。该公司计划从今年晚些时候开始进行全球监管提交，包括向美国提交补充新药申请。

Food and Drug Administration using a Priority Review Voucher. .

食品和药物管理局使用优先审查凭证。。。

Investor Webcast Information

投资者网络广播信息

Management will discuss the HELIOS-B topline results via conference call on Monday, June 24, 2024, at 8:00 am ET. To access the call, please register online at https://register.vevent.com/register/BId4cad1b9b91f4f41a7907f0222ed55c7. Participants are requested to register at a minimum of 15 minutes before the start of the call.

管理层将于2024年6月24日（星期一）美国东部时间上午8:00通过电话会议讨论HELIOS-B topline的结果。要访问该电话，请在线注册https://register.vevent.com/register/BId4cad1b9b91f4f41a7907f0222ed55c7.要求参与者在通话开始前至少15分钟登记。

A replay of the call will be available two hours after the call and archived on the same web page for six months. .

。。。

A live audio webcast of the call will be available on the Investors section of the Company’s website at www.alnylam.com/events. An archived webcast will be available on the Company’s website approximately two hours after the event.

公司网站www.alnylam.com/events的投资者部分将提供电话的实时音频网络广播。活动结束大约两小时后，公司网站将提供存档的网络广播。

IMPORTANT SAFETY INFORMATION

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。在使用AMVUTTRA治疗期间，不应给予比RDA更高的剂量，以试图达到正常的血清维生素A水平，因为血清维生素A水平不能反映体内的总维生素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 for polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) were arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).

用AMVUTTRA治疗遗传性甲状腺素转运蛋白介导的淀粉样变性多发性神经病（hATTR PN）的患者最常见的不良反应是关节痛（11%），呼吸困难（7%）和维生素A降低（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 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.

。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. .

。。。

About AMVUTTRA® (vutrisiran)

关于AMVUTTRA® （武特里斯兰）

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 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. 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.

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2006年诺贝尔生理学或医学奖的认可。

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.

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。小干扰RNA（siRNA）是介导RNAi并构成Alnylam RNAi治疗平台的分子，它通过有效沉默信使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，从而阻止了它们的产生。

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

这是一种革命性的方法，有可能改变对遗传病和其他疾病患者的护理。。。

About Alnylam Pharmaceuticals

关于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’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.

自2002年成立以来，Alnylam领导了RNAi革命，并继续实现将科学可能性变为现实的大胆愿景。Alnylam的商业RNAi治疗产品有ONPATTRO®（patisiran）、AMVUTTRA®（vutrisiran）、GIVLAARI®（givosiran）、OXLUMO®（lumasiran）和Leqvio®（inclisiran），这些产品正在由Alnylam的合作伙伴诺华开发和商业化。

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（以前的推特）@Alnylam，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, including its potential to be a transformative medicine for patients with ATTR amyloidosis with cardiomyopathy; the potential for vutrisiran to become the new standard of care 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 potential for vutrisiran to drive Alnylam’s next era of substantial growth; the expected timing of the presentation of full data from the HELIOS-B clinical trial and the filing of a 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，包括其成为ATTR淀粉样变性伴心肌病患者的转化药物的潜力；vutrisiran有可能成为治疗ATTR淀粉样变性伴心肌病的新标准；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推动Alnylam下一个大幅度增长时代的潜力；HELIOS-B临床试验完整数据提交的预期时间和美国。

Supplemental New Drug Application for vutrisiran; Alnylam’s plans to use a Priority Review Voucher in connection with the Supplemental New Drug Application for vutrisiran; the potential for vutrisiran’s clinical profile to support first-line positioning in newly diagnosed patients and in those patients who continue to experience disease progression with stabilizers; and the potential for Alnylam to achieve its Alnylam P5x25 vision of becoming a leading biopharma company should be considered forward-looking statements.

vutrisiran的补充新药申请；；vutrisiran的临床特征有可能支持新诊断患者和继续使用稳定剂进行疾病进展的患者的一线定位；Alnylam实现其成为领先生物制药公司的Alnylam P5x25愿景的潜力应被视为前瞻性声明。

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 t.

由于各种重要风险、不确定性和其他因素，包括但不限于与Alnylam的能力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的结果和未来计划存在重大差异。

View source version on businesswire.com: https://www.businesswire.com/news/home/20240624263080/en/

在businesswire.com上查看源版本：https://www.businesswire.com/news/home/20240624263080/en/

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）

617-682-4340

617-682-4340

Josh Brodsky

乔什·布罗茨基

(Investors)

（投资者）

617-551-8276

617-551-8276

Source: Alnylam Pharmaceuticals, Inc.

资料来源：Alnylam Pharmaceuticals，股份有限公司。