AMVUTTRA®（vutrisiran）显著降低ATTR淀粉样变心肌病患者死亡率及一系列重要心血管事件：HELIOS的更多数据-动脉网

AMVUTTRA® (vutrisiran) Significantly Reduces Mortality and a Range of Important Cardiovascular Events in Patients with ATTR Amyloidosis with Cardiomyopathy: Additional Data from HELIOS

阿里拉姆制药等信源发布 2025-05-17 17:51



可切换为仅中文







CAMBRIDGE, Mass.

马萨诸塞州剑桥市

--(BUSINESS WIRE)--May 17, 2025--

--（商业资讯）--2025年5月17日--

Alnylam Pharmaceuticals, Inc.

Alnylam制药公司

(Nasdaq: ALNY), the leading RNAi therapeutics company, today presented the most contemporary analysis of the HELIOS-B Phase 3 study of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM) as a late-breaking abstract at the Heart Failure 2025

(Nasdaq: ALNY)，领先的RNAi治疗公司，今天在2025年心力衰竭会议上以最新突破性摘要的形式展示了vutrisiran用于治疗伴有心肌病的ATTR淀粉样变性（ATTR-CM）的HELIOS-B第三阶段研究的最新分析。

Congress

国会

, a scientific congress of the

，一个科学大会的

European Society of Cardiology

欧洲心脏病学会

, taking place

，发生地点

May 17-20

5月17日至20日

in Belgrade,

在贝尔格莱德，

Serbia

塞尔维亚

. The results demonstrate that vutrisiran, which rapidly knocks down transthyretin, reduces key cardiovascular (CV) events such as CV hospitalizations, and heart failure (HF) hospitalizations. Additionally, in the analysis, urgent HF visits were reduced by 46% (95% CI: 0.30, 0.98; p = 0.041) in the overall population during the double-blind period, compared to placebo.

结果表明，vutrisiran 能够迅速降低转甲状腺素蛋白水平，减少主要心血管 (CV) 事件，如心血管住院和心力衰竭 (HF) 住院。此外，在分析中，与安慰剂相比，整个研究群体在双盲期间的紧急心衰就诊减少了 46%（95% 置信区间：0.30, 0.98；p = 0.041）。

These CV events often precede all-cause mortality (ACM) and are key indicators of disease progression. .

这些心血管事件常常发生在全因死亡率（ACM）之前，并且是疾病进展的关键指标。

Importantly, results from the

重要的是，结果来自于

November 2024

2024年11月

data cut, including further follow up through up to 42 months, reinforce the primary HELIOS-B analysis showing vutrisiran’s effect on ACM, and further demonstrate that vutrisiran reduces CV mortality. Through 42 months, the risk of ACM was reduced by 36% (95% CI: 0.46, 0.88; p = 0.007) and the risk of CV mortality was reduced by 33% (95% CI: 0.47, 0.96; p = 0.038) in the overall population, compared to placebo.

数据截止，包括长达42个月的进一步随访，强化了主要的HELIOS-B分析，显示了vutrisiran对全因死亡率（ACM）的影响，并进一步证明vutrisiran降低了心血管（CV）死亡率。在总人群中，与安慰剂相比，截至42个月时，全因死亡率的风险降低了36%（95%置信区间：0.46, 0.88；p = 0.007），心血管死亡率的风险降低了33%（95%置信区间：0.47, 0.96；p = 0.038）。

For both the primary analysis and the current analysis, vital status through 42 months was ascertained for over 99% of all randomized patients from the HELIOS-B study, underscoring the robustness of the results. .

对于主要分析和当前分析，从HELIOS-B研究中随机抽取的患者中超过99%的患者在42个月时的生命状态已确定，这凸显了结果的稳健性。

The study was conducted in a contemporary patient population with patients receiving robust background therapy, inclusive of treatment with a TTR stabilizer and SGLT2 inhibitors. The analysis of the HELIOS-B Phase 3 study, including mortality data through up to 42 months, was simultaneously published in.

该研究在当代患者群体中进行，患者接受了包括TTR稳定剂和SGLT2抑制剂在内的有效背景治疗。对HELIOS-B第三阶段研究的分析，包括长达42个月的死亡率数据，同时发表在。

JACC

。

“From the primary analysis of HELIOS-B, we know that AMVUTTRA profoundly impacts all-cause mortality, while preserving patients’ functional capacity and quality of life,” said

“从HELIOS-B的主要分析中，我们知道AMVUTTRA对全因死亡率有深远影响，同时保留了患者的功能能力和生活质量，”

Pushkal Garg

普什卡尔·加格

, M.D., Chief Medical Officer of

，医学博士，首席医疗官

Alnylam

阿尔尼拉姆

. “These new data—including the impact on mortality, on cardiovascular events and on urgent heart failure visits, the latter of which was reduced by nearly half—add to the story of consistency and magnitude of benefit. I remain impressed by the HELIOS-B results, which are noteworthy given the substantial use of heart failure treatments in the study population, and I believe they continue to reinforce AMVUTTRA as a clinically differentiated, first-line option for patients with ATTR-CM.” .

“这些新数据——包括对死亡率、心血管事件和紧急心衰就诊的影响，其中后者减少了近一半——进一步增强了疗效一致性和显著性的证据。我依然对HELIOS-B的结果印象深刻，鉴于研究人群中大量使用了心衰治疗手段，这些结果尤为值得注意。我相信它们继续巩固了AMVUTTRA作为ATTR-CM患者临床差异化的首选方案的地位。”

The results from the analysis underscore the rapid and sustained benefits of vutrisiran in treating ATTR-CM across key endpoints:

分析结果强调了vutrisiran在治疗ATTR-CM方面跨越关键终点的快速且持续的益处：

In a separate presentation on

在另一场演讲中

Tuesday, May 20

5月20日，星期二

，

Alnylam

阿尔尼拉姆

will share findings from a subgroup analysis of HELIOS-B evaluating the impact of vutrisiran on ACM and recurrent CV events among patients identified by investigators as having experienced disease progression while being treated with tafamidis.

将分享HELIOS-B亚组分析的结果，评估维特立森对研究者认定的在使用他法米迪治疗期间出现疾病进展的患者全因死亡率（ACM）和复发性心血管事件的影响。

Also at the Heart Failure 2025

同样在2025年心力衰竭会议

Congress

国会

，

Alnylam

阿尔尼拉姆

will present the study design and rationale for TRITON-CM, a Phase 3, randomized, double-blind, study of nucresiran in patients with ATTR-CM. Nucresiran is an investigational next-generation RNAi therapeutic targeting TTR that has been shown to deliver rapid knockdown of TTR greater than 95% with twice-annual dosing in a Phase 1 study.

将介绍TRITON-CM的试验设计和理由，这是一项针对ATTR-CM患者的三期、随机、双盲研究，涉及药物nucresiran。Nucresiran是一种研究中的新一代RNAi治疗药物，靶向TTR，在一期研究中已显示出每年两次给药可使TTR降低超过95%的效果。

TRITON-CM is an event-driven CV outcomes trial with a primary endpoint of composite ACM and CV events. The study is on track to initiate in the first half of 2025 and will enroll approximately 1,200 patients with wild-type or variant TTR and confirmed cardiomyopathy, including those receiving background stabilizer therapy.

TRITON-CM 是一项事件驱动的心血管结局试验，其主要终点是复合全因死亡率 (ACM) 和心血管事件。该研究有望在 2025 年上半年启动，将招募大约 1,200 名野生型或变异型 TTR 并确诊心肌病的患者，包括那些接受背景稳定剂治疗的患者。

Additional details of the study’s secondary endpoints and key inclusion and exclusion criteria will be shared on .

该研究的次要终点以及关键的纳入和排除标准的更多细节将会在共享。

Monday, May 19

5月19日，星期一

。

AMVUTTRA

(vutrisiran) was approved by the

（vutrisiran）已获得批准

U.S. Food and Drug Administration

美国食品药品监督管理局

(FDA) and the

（FDA）和

Brazilian Health Regulatory Agency

巴西卫生监管局

(ANVISA) for treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults.

巴西国家卫生监督局 (ANVISA) 批准用于治疗成人野生型或遗传性转甲状腺素蛋白介导的淀粉样变性心肌病。

The Committee for Medicinal Products

药品产品委员会

for Human Use (CHMP) of the

供人使用（CHMP）的

European Medicines Agency

欧洲药品管理局

(EMA) has adopted a positive opinion recommending the approval of vutrisiran for the same indication. A formal regulatory decision by the

欧洲药品管理局（EMA）已采纳积极意见，推荐批准vutrisiran用于相同适应症。

European Commission of the EMA

欧洲药品管理局（EMA）的欧洲委员会

is expected by the third quarter of 2025. Vutrisiran is currently under review for the treatment of ATTR-CM by the

预计到2025年第三季度。Vutrisiran目前正接受用于治疗ATTR-CM的审查。

Japanese Pharmaceuticals

日本制药公司

and

和

Medical Devices Agency

医疗器械管理局

(PMDA).

（PMDA）。

Alnylam

阿尔尼拉姆

remains on track to proceed with additional global regulatory submissions for vutrisiran in 2025 and beyond.

仍然按计划在2025年及以后继续进行vutrisiran的更多全球监管提交。

For additional information on Alnylam’s presentations at the Heart Failure 2025

有关Alnylam在2025年心力衰竭会议上的报告的更多信息

Congress

国会

, please visit

，请访问

Capella

御夫座

。

Indications and Important Safety Information

适应症和重要的安全信息

Indications Approved by the

批准的适应症

U.S.

美国

FDA

食品药品监督管理局

AMVUTTRA

(vutrisiran) is indicated for the treatment of the:

(vutrisiran) 适用于治疗：

Important Safety Information

重要安全信息

Reduced Serum Vitamin A Levels and Recommended Supplementation

血清维生素A水平降低及推荐的补充措施

AMVUTTRA treatment leads to a decrease in serum vitamin A levels.

AMVUTTRA治疗会导致血清维生素A水平下降。

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. .

建议服用AMVUTTRA的患者补充推荐每日摄入量（RDA）的维生素A。在使用AMVUTTRA治疗期间，不应为了使血清维生素A水平恢复正常而给予高于RDA的剂量，因为血清维生素A水平并不能反映体内总维生素A含量。

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（如夜盲症），应转诊给眼科医生。

Adverse Reactions

不良反应

In a study of patients with hATTR-PN, 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%).

在对患有hATTR-PN的患者进行的研究中，接受AMVUTTRA治疗的患者最常见的不良反应是四肢疼痛（15%）、关节痛（11%）、呼吸困难（7%）和维生素A降低（7%）。

In a study of patients with ATTR-CM, no new safety issues were identified.

在一项针对ATTR-CM患者的研究中，未发现新的安全问题。

For additional information about AMVUTTRA, please see the full

有关 AMVUTTRA 的更多信息，请参阅完整内容

U.S.

美国

Prescribing Information

处方信息

(revised

（修订版

March 2025

2025年3月

)

About AMVUTTRA

关于AMVUTTRA

(vutrisiran)

（维特希兰）

AMVUTTRA

(vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of variant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, vutrisiran is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.

(vutrisiran) 是一种 RNAi 治疗药物，能够快速减少变异型和野生型转甲状腺素蛋白 (TTR)，针对转甲状腺素蛋白 (ATTR) 淀粉样变性的根本原因。vutrisiran 通过皮下注射每季度给药一次，已在超过 15 个国家获批并上市，用于治疗成人遗传性转甲状腺素蛋白介导的淀粉样变性多发性神经病 (hATTR-PN)。

In .

在。

Europe

欧洲

, it is administered as a subcutaneous injection once every three months, either by a healthcare professional, or self-administered by patients or their caregivers. 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. .

，它每三个月通过皮下注射给药一次，可以由医疗专业人员进行注射，也可以由患者或其护理人员自行注射。Vutrisiran也正在开发用于治疗伴有心肌病的ATTR淀粉样变性（ATTR-CM），这包括野生型和遗传型两种形式的疾病。

About ATTR

关于ATTR

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.

转甲状腺素蛋白淀粉样变性（ATTR）是一种诊断不足、进展迅速、致残且致命的疾病，由错误折叠的转甲状腺素蛋白（TTR）引起，这些蛋白在身体的各个部位（包括神经、心脏和胃肠道）以淀粉样沉积物的形式积累。患者可能出现多发性神经病、心肌病或两种疾病表现同时存在的情况。

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..

ATTR有两种不同的形式——遗传性ATTR（hATTR），由TTR基因变异引起，全球大约有5万人受到影响；以及野生型ATTR（wtATTR），它在没有TTR基因变异的情况下发生，全球估计有20万至30万人受到影响。

1-4

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）是一种天然的基因沉默细胞过程，代表了当今生物学和药物开发中最有前途且进展最快的前沿领域之一。它的发现被誉为“每十年左右才会出现一次的重大科学突破”，并因此获得了2006年诺贝尔生理学或医学奖。

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天然生物过程RNAi，一类被称为RNAi治疗药物的新药已经成为现实。小干扰RNA（siRNA）是介导RNAi的分子，也是Alnylam的RNAi治疗平台的组成部分，它通过有效沉默信使RNA（mRNA）——即编码致病或疾病通路蛋白质的遗传前体——从而在现有药物的上游发挥作用，防止这些蛋白质的生成。

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

这是一项革命性的方法，有潜力转变对遗传及其他疾病患者的护理。

About

关于

Alnylam Pharmaceuticals

Alnylam制药公司

Alnylam

阿尔尼拉姆

(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.

(Nasdaq: ALNY) 已引领将RNA干扰（RNAi）转化为一类全新创新药物的开发，这些药物有潜力改变那些患有罕见及常见未满足需求疾病的患者生活。基于诺贝尔奖获奖科学成果，RNAi疗法代表了一种强大且经过临床验证的方法，能够带来变革性的治疗药物。

Since its founding in 2002, .

自从它在 2002 年成立以来，。

Alnylam

阿尼兰姆

has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality.

引领了RNAi革命，并继续致力于实现将科学可能性变为现实的大胆愿景。

Alnylam

阿尔尼拉姆

has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development.

拥有一个深入的在研药物管道，包括多个处于后期开发阶段的产品候选药物。

Alnylam

阿尔尼拉姆

is executing on its “

正在执行其“

Alnylam P

阿尼拉姆 P

x25

” 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.

“通过可持续创新和卓越的财务表现，提供在罕见病和常见病领域具有变革性的药物，惠及全球患者，从而打造领先的生物技术形象。”

Alnylam

阿尔尼拉姆

is headquartered in

总部位于

Cambridge, MA.

马萨诸塞州剑桥市

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-CM, including the ability of vutrisiran to reduce mortality and cardiovascular events in ATTR-CM patients and to preserve patients’ functional capacity and quality of life; the potential for vutrisiran to become a first-line therapy for ATTR-CM; the timing of the initiation of the TRITON-CM study and the number of patients who will be enrolled in that study; the timing of additional global regulatory submissions for vutrisiran; the timing or receipt of any additional regulatory approvals for vutrisiran for ATTR-CM; Alnylam’s ability to execute on its “.

本新闻稿包含1933年《证券法》第27A条和1934年《证券交易法》第21E条所指的前瞻性陈述。所有非历史事实的陈述，包括关于Alnylam的预期、信念、目标、计划或前景的陈述，均涉及Alnylam对vutrisiran治疗ATTR-CM的安全性和有效性的预期，包括vutrisiran减少ATTR-CM患者死亡率和心血管事件的能力，以及维持患者的功能能力和生活质量；vutrisiran成为ATTR-CM一线疗法的潜力；TRITON-CM研究的启动时间及该研究中将招募的患者数量；vutrisiran在全球范围内提交额外监管申请的时间；vutrisiran针对ATTR-CM可能获得的任何其他监管批准的时间或结果；Alnylam执行其“。

Alnylam P

阿尼兰P

x25

” strategy and to deliver transformative medicines in both rare and common diseases benefit patients around the world through sustainable innovation and exceptional financial performance; and Alnylam’s ability to have a leading biotech profile should be considered forward-looking statements.

“战略，并通过可持续创新和卓越的财务表现，在罕见病和常见病领域提供变革性药物，造福全球患者；以及Alnylam具备领先的生物技术公司地位的能力，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 to successfully execute on its “.

实际结果和未来计划可能与这些前瞻性陈述中指出的内容存在重大差异，这是由于各种重要的风险、不确定性和其他因素，包括但不限于与Alnylam成功执行其“计划相关”的风险和不确定性。

Alnylam P

阿尼兰P

x25

” strategy; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation; the potential risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2024 Annual Report on Form 10-K filed with the .

“战略；Alnylam发现和开发新型候选药物及递送方法并成功证明其候选产品有效性和安全性的能力；Alnylam候选产品的临床前和临床结果；监管机构的行为或建议以及Alnylam为其候选产品获得并保持监管批准的能力，以及获得有利的定价和报销；在全球范围内成功推出、营销和销售Alnylam的获批产品；Alnylam候选产品或其上市产品的生产与供应中的延迟、中断或失败；获取、维护和保护知识产权；Alnylam通过对其运营的纪律性投资来管理增长和运营开支的能力，及其未来实现财务自给自足的能力；Alnylam维持战略性业务合作的能力；Alnylam对第三方在某些产品的开发和商业化上的依赖；诉讼的结果；未来政府调查的潜在风险；以及意外支出；还包括在Alnylam提交的2024年度10-K表年报中‘风险因素’部分更全面讨论的那些风险。”

Securities and Exchange Commission

证券交易委员会

(SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that

（SEC），可能会在Alnylam随后的10-Q表季度报告中不时更新，并在其他文件中有所体现。

Alnylam

阿尔尼拉姆

makes with the

与...一起制作

SEC

证券交易委员会

. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing Alnylam’s views as of any subsequent date.

此外，任何前瞻性声明仅代表Alnylam截至今日的观点，不应被视为代表Alnylam在任何后续日期的观点。

Alnylam

阿尔尼拉姆

explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

明确拒绝任何义务，除非法律要求，否则不会更新任何前瞻性陈述。

Hawkins PN, Ando Y, Dispenzeri A, et al.

霍金斯 PN，安藤 Y，迪斯彭泽里 A，等。

Ann Med

医学年鉴

. 2015;47(8):625-638.

Gertz MA.

格茨 MA。