CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that two new data sets from the HELIOS-B Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), were presented in the Late Breaking Clinical Research Session 1 at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2024, which was held virtually.

领先的RNAi治疗公司Alnylam Pharmaceuticals，Inc.（纳斯达克：ALNY）今天宣布，来自vutrisiran的HELIOS-B 3期研究的两个新数据集，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，已在2024年美国心力衰竭学会（HFSA）年度科学会议上的最新临床研究会议1上发表，该会议实际上举行了。

An open access recording of Alnylam presentations will be available on the HFSA website following the session..

会议结束后，将在HFSA网站上提供Alnylam演讲的开放获取录音。。

Progression in ATTR-CM is associated with cardiac wall thickening, deterioration in systolic and diastolic function and increases in biomarkers of cardiac stress and injury, NT-pro-BNP and Troponin I.

ATTR-CM的进展与心壁增厚，收缩和舒张功能恶化以及心脏应激和损伤生物标志物NT-pro-BNP和肌钙蛋白I的增加有关。

“Consistent with demonstrated improvements in outcomes and health status, these new data show that vutrisiran attenuated measures of disease progression across multiple domains of cardiac structure and function, NT-proBNP and troponin I, in a contemporary ATTR-CM patient population,” said Pushkal Garg, M.D., Chief Medical Officer, Alnylam.

Alnylam首席医学官Pushkal Garg医学博士说：“与结果和健康状况的改善相一致，这些新数据表明，vutrisiran减弱了当代ATTR-CM患者群体心脏结构和功能多个领域的疾病进展测量，NT-proBNP和肌钙蛋白I。”。

“These data demonstrate that rapid knockdown of TTR leads to an early impact on cardiac biomarkers and echocardiographic parameters, indicative of a potential disease-modifying effect, and underscores the benefit of treating patients with an RNAi therapeutic earlier in the course of disease. We remain confident that, with approval, vutrisiran has the potential to become a first-line therapy for ATTR amyloidosis with cardiomyopathy and are on track to complete multiple global regulatory submissions before the end of the year.”.

“这些数据表明，TTR的快速敲低会对心脏生物标志物和超声心动图参数产生早期影响，表明潜在的疾病缓解作用，并强调了在疾病早期使用RNAi治疗患者的益处。我们仍然相信，经过批准，vutrisiran有可能成为ATTR淀粉样变性伴心肌病的一线治疗药物，并有望在年底前完成多项全球监管提交。”。

Analysis results

分析结果

New echocardiographic data demonstrated that treatment with vutrisiran slowed disease progression in a contemporary population of patients with ATTR-CM across multiple domains of cardiac structure and diastolic and systolic function at Month 30 as compared to placebo. The magnitude of the treatment effects with vutrisiran compared to placebo were similar or greater in the monotherapy population.

新的超声心动图数据表明，与安慰剂相比，vutrisiran治疗在30个月时在心脏结构和舒张和收缩功能的多个领域减缓了当代ATTR-CM患者的疾病进展。在单药治疗人群中，与安慰剂相比，vutrisiran的治疗效果相似或更大。

Significant improvements in both diastolic and systolic function were observed as early as 12 months and 18 months, respectively, in the overall population. The Month 30 results in the overall population are detailed in the table below.*.

在总体人群中，分别在12个月和18个月时观察到舒张和收缩功能的显着改善。下表详细列出了30个月总人口的结果。*。

Overall population

总人口

N=654

N=654

Cardiac Wall Structure

心壁结构

Mean Left Ventricular Wall Thickness

平均左心室壁厚

Change from Baseline, cm

相对于基线的变化，cm

LS Mean difference (Vutrisiran – Placebo)

LS平均差异（Vutrisiran–安慰剂）

-0.04 cm

-0.04厘米

p=0.03

p=0.03

Left Ventricular Mass Index

左心室质量指数

Change from Baseline, g/m2

相对于基线的变化，克/平方米

LS Mean difference (Vutrisiran – Placebo)

LS平均差异（Vutrisiran–安慰剂）

-10.6 g/m2

-10.6克/平方米

p=0.0047

p=0.0047

Left Ventricular Diastolic Function

E/A Ratio

资产负债率

Change from Baseline

从基线更改

LS Mean difference (Vutrisiran – Placebo)

LS平均差异（Vutrisiran–安慰剂）

-0.29

-0.29

p=0.0434

p=0.0434

E/e’ Ratio

E/E’比率

Change from Baseline

从基线更改

LS Mean difference (Vutrisiran – Placebo)

LS平均差异（Vutrisiran–安慰剂）

-1.82

-1.82

p=0.00003

p=0.00003

TDI Lateral e’

TDI横向e'

Change from Baseline, cm/s

相对于基线的变化，厘米/秒

LS Mean ± SEM

LS平均值±SEM

0.55 cm/s

0.55厘米/秒

p=0.0005

p=0.0005

Left Ventricular Systolic Function

左心室收缩功能

Left Ventricular Ejection Fraction

左心室射血分数

Change from Baseline, %

与基线相比的变化，%

LS Mean difference (Vutrisiran – Placebo)

LS平均差异（Vutrisiran–安慰剂）

2.03%

2.03%

p=0.02

p=0.02

Absolute Global Longitudinal Strain

绝对整体纵向应变

Change from Baseline, %

与基线相比的变化，%

LS Mean difference (Vutrisiran – Placebo)

LS平均差异（Vutrisiran–安慰剂）

1.23%

1.23%

p=0.000002

Left Ventricular Stroke Volume

Change from Baseline, mL

与基线相比的变化，mL

LS Mean difference (Vutrisiran – Placebo)

LS平均差异（Vutrisiran–安慰剂）

4.05 mL

4.05毫升

p=0.0007

*All p-values included within the table are nominal p-values.

*表中包含的所有p值均为标称p值。

In addition, analyses of cardiac biomarkers NT-proBNP and troponin I were also presented. At Month 30, the relative reduction in the fold change in NT-proBNP in patients treated with vutrisiran compared to placebo was 32% in the overall population and 43% in the monotherapy population (adjusted geometric mean fold change ratio [vutrisiran/placebo]: 0.68; nominal p-value 3.440E-12 and 0.57; nominal p-value 4.339E-12, respectively).

此外，还介绍了心脏生物标志物NT-proBNP和肌钙蛋白I的分析。在第30个月，与安慰剂相比，接受vutrisiran治疗的患者NT-proBNP倍数变化的相对减少率在总体人群中为32%，在单药治疗人群中为43%（调整后的几何平均倍数变化率[vutrisiran/安慰剂]：0.68；标称p值分别为3.440E-12和0.57；标称p值分别为4.339E-12）。

At Month 30, relative reduction in the fold change of troponin I was 32% in the overall population and 45% in the monotherapy population (adjusted geometric mean fold change ratio [vutrisiran/placebo]: 0.68; nominal p-value 1.566E-14 and 0.55; nominal p-value 9.684E-17, respectively)..

在第30个月，肌钙蛋白I倍数变化的相对减少在总体人群中为32%，在单药治疗人群中为45%（调整后的几何平均倍数变化率[vutrisiran/安慰剂]：0.68；标称p值1.566E-14和0.55；标称p值分别为9.684E-17）。。

In the subgroup of patients receiving tafamidis at baseline, a relative reduction in the fold change of 18% was observed in NT-proBNP and 10% in troponin I (adjusted geometric mean fold change ratio [vutrisiran/placebo]: 0.82; nominal p-value 0.0045 and 0.90; nominal p-value 0.0849, respectively) at Month 30.

在基线时接受他法米地治疗的患者亚组中，NT-proBNP的倍数变化相对减少了18%，肌钙蛋白I的倍数变化相对减少了10%（调整后的几何平均倍数变化比[vutrisiran/安慰剂]：0.82；标称p值分别为0.0045和0.90；标称p值分别为0.0849）。

For both NTproBNP and troponin I, patients treated with vutrisiran demonstrated nominally significant reductions relative to placebo at 6 months. These results were consistent across all pre-specified subgroups, with a larger treatment effect observed in the monotherapy population..

对于NTproBNP和肌钙蛋白I，接受vutrisiran治疗的患者在6个月时相对于安慰剂表现出名义上的显着降低。这些结果在所有预先指定的亚组中都是一致的，在单一疗法人群中观察到更大的治疗效果。。

Detailed results from the HELIOS-B study were presented at the European Society of Cardiology annual congress on August 30, 2024, and simultaneously published in The New England Journal of Medicine.

HELIOS-B研究的详细结果于2024年8月30日在欧洲心脏病学会年会上发表，同时发表在《新英格兰医学杂志》上。

Alnylam plans to include a discussion of these data at its upcoming TTR Investor Day on Wednesday, October 9, 2024, at 8:30 am ET in New York City. 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..

Alnylam计划于2024年10月9日（星期三）美国东部时间上午8:30在纽约举行的TTR投资者日（TTR Investor Day）上讨论这些数据。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。。

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..

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 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®（vutrisiran）是一种RNAi治疗剂，可快速敲除突变型和野生型运甲状腺素蛋白（TTR），解决运甲状腺素蛋白（ATTR）淀粉样变性的根本原因。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），由TTR基因变异引起，影响全球约50000人，和野生型ATTR（wtATTR），其发生时没有TTR基因变异，影响全球约200000-300000人。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.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，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.

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，从而形成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, including its potential to become a first-line therapy for patients with ATTR amyloidosis with cardiomyopathy, and the timing of Alnylam’s global regulatory submissions for vutrisiran should be considered forward-looking statements.

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。除了关于Alnylam的期望、信念、目标、计划或前景的历史事实陈述之外的所有陈述，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一线治疗的潜力，以及Alnylam对vutrisiran的全球监管提交的时间，都应被视为前瞻性陈述。

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 its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; and any delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2023 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may .

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为其候选产品（包括vutrisiran）获得监管批准的能力，以及优惠的定价和报销；在全球成功推出、营销和销售Alnylam批准的产品；以及Alnylam候选产品或其上市产品的制造和供应中的任何延误、中断或故障；以及在Alnylam 2023年年度报告（表格10-K）中提交给美国证券交易委员会（SEC）的“风险因素”中更充分讨论的风险。

1 Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med. 2015;47(8):625-638.

1 Hawkins PN，Ando Y，Dispenzeria等人。Ann Med。2015年；47（8）：625-638。

2 Gertz MA. Am J Manag Care. 2017;23(7):S107-S112.

2 Gertz MA.Am J Manag Care。2017年；23（7）：S107-S112。

3 Conceicao I, Gonzalez-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21:5-9.

3 Conceicao I、Gonzalez Duarte A、Obici L等。2016年；21:5-9。

4 Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.

4 Ando Y、Coelho T、Berk JL等，《孤儿院J》罕见的Dis。2013年；8:31。

5 Elbashir SM, Harborth J, Lendeckel W, et al. Nature. 2001;411(6836):494-498.

5 Elbashir SM、Harborth J、Lendeckel W等，《自然》。2001年；411（6836）：494-498。

6 Zamore P. Cell. 2006;127(5):1083-1086.

6 Zamore P.细胞。2006年；127（5）：1083-1086。