CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the KARDIA-2 Phase 2 study of zilebesiran, an investigational RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of hypertension, met the primary endpoint showing that zilebesiran resulted in clinically and statistically significant additive, placebo-adjusted reductions in 24-hour mean systolic blood pressure (SBP) at Month 3 as measured by ambulatory blood pressure monitoring (ABPM) in each of three independent patient cohorts receiving the standardized background therapies of either a thiazide-like diuretic (indapamide), calcium channel blocker (amlodipine) or angiotensin receptor blocker (olmesartan).

马萨诸塞州剑桥市。-（商业新闻短讯）--领先的RNAi治疗公司Alnylam Pharmaceuticals，Inc.（纳斯达克：ALNY）今天宣布，zilebesiran的KARDIA-2 2期研究，zilebesiran是一种针对肝脏表达血管紧张素原（AGT）的RNAi治疗药物，正在开发用于治疗高血压，达到了主要终点，表明齐莱贝西仑在接受噻嗪类利尿剂（吲达帕胺）标准化背景治疗的三个独立患者队列中，通过动态血压监测（ABPM）测量，在第3个月时，24小时平均收缩压（SBP）在临床和统计学上显着降低，钙通道阻滞剂（氨氯地平）或血管紧张素受体阻滞剂（奥美沙坦）。

Zilebesiran demonstrated an encouraging safety and tolerability profile when added to these standard of care antihypertensives. The Company believes these findings support further development..

当添加到这些标准护理抗高血压药中时，齐莱贝西兰表现出令人鼓舞的安全性和耐受性。该公司认为这些发现有助于进一步发展。

“We are thrilled that a single dose of zilebesiran achieved clinically significant, additional reductions in systolic blood pressure when administered to patients who are not adequately controlled with commonly prescribed antihypertensives,” said Simon Fox, Ph.D., Vice President, Zilebesiran Program Lead at Alnylam.

Alnylam zilebesiran项目负责人西蒙·福克斯（SimonFox）博士说：“我们很高兴单剂量的zilebesiran在临床上显着降低了收缩压，这些患者在服用常用抗高血压药物后没有得到充分控制。”

“These KARDIA-2 results, showing durable additional levels of blood pressure reduction on top of what is achieved by standard of care first-line antihypertensives with an encouraging safety profile, reinforce our confidence in zilebesiran’s differentiated profile. We look forward to sharing the full KARDIA-2 data as a late-breaking clinical trial at the upcoming American College of Cardiology Annual Scientific Session.”.

“这些KARDIA-2的结果显示，除了标准护理一线抗高血压药所达到的血压降低水平外，还具有令人鼓舞的安全性，这增强了我们对zilebesiran差异化特征的信心。我们期待着在即将到来的美国心脏病学院分享完整的KARDIA-2数据，作为一项最新的临床试验年度科学会议”。

The KARDIA-2 Phase 2 study is a randomized, double-blind (DB), placebo-controlled study designed to evaluate the efficacy and safety of zilebesiran, when added to standard of care antihypertensive medications, in adults with mild-to-moderate hypertension. This global, multicenter study enrolled 672 adults with hypertension.

KARDIA-2 2期研究是一项随机，双盲（DB），安慰剂对照研究，旨在评估齐利贝西兰在轻度至中度高血压患者中加入标准护理抗高血压药物后的疗效和安全性。这项全球多中心研究招募了672名患有高血压的成年人。

Patients who met all inclusion criteria and none of the exclusion criteria during a screening period were first randomized into three different cohorts to receive open-label therapy with olmesartan, amlodipine or indapamide as their protocol-specified background antihypertensive medication during a run-in period of at least four weeks.

在筛查期间符合所有纳入标准且没有排除标准的患者首先被随机分为三个不同的队列，在至少四周的磨合期内接受奥美沙坦，氨氯地平或吲达帕胺作为其方案指定的背景抗高血压药物的开放标签治疗。

Following the run-in period, eligible patients were randomized 1:1 to receive 600 mg zilebesiran or placebo in addition to their protocol-specified background antihypertensive medication for six months..

磨合期后，符合条件的患者以1:1的比例随机接受600 mg齐莱贝西仑或安慰剂，以及他们的方案指定的背景抗高血压药物治疗6个月。

The primary endpoint is the change from baseline in mean SBP at Month 3, assessed by 24-hour ABPM. Additional endpoints include the change in 24-hour mean SBP after six months of treatment assessed by ABPM, change in office SBP at Month 3 and Month 6, and change in diastolic blood pressure (DBP) measured by ABPM and office blood pressure at Month 3 and Month 6.

主要终点是第3个月平均SBP从基线的变化，通过24小时ABPM评估。其他终点包括ABPM评估治疗6个月后24小时平均SBP的变化，第3个月和第6个月办公室SBP的变化，以及第3个月和第6个月ABPM测量的舒张压（DBP）和办公室血压的变化。第6个月。

Safety will be assessed throughout the study..

安全性将在整个研究过程中进行评估。

Alnylam and Roche today also announced the initiation of the global KARDIA-3 (NCT06272487) Phase 2 study, a randomized, DB, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of zilebesiran used as an add-on therapy in adult patients with high cardiovascular risk and uncontrolled hypertension despite treatment with two to four standard of care antihypertensive medications.

Alnylam和Roche今天还宣布启动全球KARDIA-3（NCT06272487）2期研究，这是一项随机，DB，安慰剂对照，多中心研究旨在评估zilebesiran作为附加疗法用于高心血管风险和未控制高血压的成年患者的疗效和安全性，尽管使用了两到四种标准的抗高血压药物治疗。

Patients with estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73m2 will be enrolled to cohort A, and patients with eGFR 30 to <45 mL/min/1.73m2 will be enrolled to cohort B. Patients who meet all of the inclusion and none of the exclusion criteria after the screening period will be randomized to receive 300 or 600 mg zilebesiran or placebo in cohort A on day 1, or 150, 300, or 600 mg zilebesiran or placebo in cohort B on day 1, of a 6-month DB treatment period as add-on therapy to their background antihypertensive medications.

估计肾小球滤过率（eGFR）≥45 mL/min/1.73m2的患者将被纳入队列A，eGFR 30至<45 mL/min/1.73m2的患者将被纳入队列B。符合所有纳入标准且筛查期后无排除标准的患者将被随机分配在第1天或第150300天在队列A中接受300或600 mg齐莱贝西仑或安慰剂，或在为期6个月的DB治疗期的第1天在队列B中服用600 mg齐莱贝西仑或安慰剂，作为其背景抗高血压药物的附加疗法。

After the 6-month DB treatment period, patients will enter the 6-month safety follow-up period..

在6个月的DB治疗期后，患者将进入6个月的安全随访期。

The primary endpoint is the change from baseline at Month 3 in mean seated office SBP. Additional endpoints include change from baseline at Month 3 in 24-hour mean SBP assessed by ABPM, change from baseline at Month 6 in mean seated office SBP and in 24-hour mean SBP assessed by ABPM. Safety will be assessed throughout the study..

主要终点是第3个月平均就座办公室SBP与基线的变化。其他终点包括ABPM评估的24小时平均SBP从第3个月的基线变化，平均坐位办公室SBP和ABPM评估的24小时平均SBP从第6个月的基线变化。安全性将在整个研究过程中进行评估。

About Zilebesiran

关于Zilebesiran

Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertension in high unmet need populations. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a demonstrated role in blood pressure (BP) regulation and its inhibition has well-established anti-hypertensive effects.

Zilebesiran是一种针对血管紧张素原（AGT）的研究性皮下给药RNAi治疗剂，正在开发中，用于治疗高度未满足需求人群的高血压。AGT是肾素-血管紧张素-醛固酮系统（RAAS）中最上游的前体，RAAS是一种在血压（BP）调节中具有明显作用的级联反应，其抑制作用具有公认的抗高血压作用。

Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes Alnylam’s Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables infrequent subcutaneous dosing with increased selectivity and the potential to achieve tonic blood pressure control demonstrating consistent and durable blood pressure reduction throughout a 24-hour period, sustained up to six months after a single dose of zilebesiran.

Zilebesiran抑制肝脏中AGT的合成，可能导致AGT蛋白的持续减少，最终导致血管收缩剂血管紧张素（Ang）II的持续减少。齐利贝西兰利用Alnylam的增强稳定化学加（ESC+）GalNAc缀合物技术，该技术可实现不频繁的皮下给药，具有更高的选择性和实现强直性血压控制的潜力，在24小时内表现出持续和持久的血压降低，单剂量齐利贝西兰后持续长达六个月。

The safety and efficacy of zilebesiran have not been established or evaluated by the FDA, EMA or any other health authority. Zilebesiran is being co-developed and co-commercialized by Alnylam and Roche..

FDA，EMA或任何其他卫生当局尚未确定或评估齐莱贝西仑的安全性和有效性。Zilebesiran正在由Alnylam和Roche共同开发和共同商业化。

About Hypertension

关于高血压

Uncontrolled hypertension is the chronic elevation of blood pressure (BP), defined by the 2017 ACC/AHA guidelines as ≥130 mmHg systolic blood pressure (SBP) and ≥80 mmHg diastolic blood pressure (DBP). More than one billion people worldwide live with hypertension.i Approximately one in three adults are living with hypertension worldwide, with up to 80% of individuals remaining uncontrolled despite the availability of several classes of oral anti-hypertensive treatments.

不受控制的高血压是血压（BP）的慢性升高，2017年ACC/AHA指南将其定义为收缩压（SBP）≥130 mmHg和舒张压（DBP）≥80 mmHg。全世界有超过10亿人患有高血压。我全世界大约有三分之一的成年人患有高血压，尽管有几类口服抗高血压治疗，但高达80%的人仍然无法控制。

Despite the availability of anti-hypertensive medications, there remains a significant unmet medical need, especially given the poor rates of adherence to existing daily oral medications, resulting in inconsistent BP control and an increased risk for stroke, heart attack and premature death.ii In particular, there are a number of high unmet need settings where novel approaches to hypertension warrant additional development focus, including patients with poor medication adherence and in patients with high cardiovascular risk..

尽管有抗高血压药物可用，但仍然存在大量未满足的医疗需求，特别是考虑到对现有每日口服药物的依从率很低，导致血压控制不一致，中风，心脏病发作和过早死亡的风险增加，有许多高度未满足的需求环境，其中高血压的新方法需要额外的发展重点，包括药物依从性差的患者和心血管风险高的患者。

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，有可能改变遗传病和其他疾病患者的护理方式。

About Alnylam Pharmaceuticals

关于Alnylam Pharmaceuticals

Alnylam Pharmaceuticals (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 Pharmaceuticals（纳斯达克：ALNY）已将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治疗产品是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。