ZENITH: A Phase 3 Global, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Zilebesiran in Addition to Standard of Care in Reducing Major Adverse Cardiovascular Events in Adult Patients With Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease

The purpose of this study is to evaluate whether zilebesiran versus placebo reduces the risk of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or heart failure (HF) events. This is an event-driven study that will continue until the targeted number of positively adjudicated primary endpoint clinical outcome events (COEs) have been reached.

Start Date22 Sep 2025

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

[+1]

NCT06675565

/ CompletedPhase 1

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of ALN-AGT01 RVR in Adult Healthy Volunteers

The purpose of this study is to evaluate the safety, tolerability and PK of single ascending doses of ALN-AGT01 RVR.

Start Date05 Nov 2024

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

NCT06423352

/ CompletedPhase 1/2

A Phase 1/2, Randomized, Double-blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacodynamics, and Pharmacokinetics of Zilebesiran in Japanese Patients With Mild to Moderate Hypertension

The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacodynamics (PD) and pharmacokinetics (PK) of zilebesiran in Japanese patients with mild to moderate hypertension.

Start Date05 Jun 2024

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

100 Clinical Results associated with Zilebesiran

100 Translational Medicine associated with Zilebesiran

100 Patents (Medical) associated with Zilebesiran

Literatures (Medical) associated with Zilebesiran

16 Sep 2025·Cureus Journal of Medical Science

Efficacy and Safety of Zilebesiran for the Management of Hypertension: An Updated Systematic Review and Meta-Analysis of Randomised Controlled Trials

Review

Author: Basit, Abdul Raffeh ; Ahmed, Muhammad Waleed ; Riaz, Chaudhry Zaid ; Chaudhry, Eymaan Riaz ; Qureshi, Ali Jamshed ; Qureshi, Muhammad Hassan ; Raza, Muhammad ; Jannat, Misha

Zilebesiran is a novel RNA interference (RNAi) therapeutic agent that reduces the production of hepatic angiotensinogen, showing promising results in the management of hypertension. However, a comprehensive assessment of its efficacy and safety is still required. This meta-analysis included four randomised controlled trials (RCTs) with 1,037 participants across the United States, Europe, and Asia, assessing single and repeat subcutaneous doses, mostly in patients on background antihypertensive therapy. The primary outcomes were change from baseline in 24-hour ambulatory and mean office blood pressure (BP) outcomes (results expressed in mmHg), adverse events, and markers of renal function. An extensive search was conducted across five electronic databases to identify RCTs assessing the clinical impact of Zilebesiran. Review Manager version 5.4 (RevMan 5.4; The Cochrane Collaboration, London, England, UK) was used to analyse data under a random-effects model, and results were reported using mean difference (MD), standardised mean difference (SMD), and odds ratio (OR) with 95% confidence intervals (CI). Zilebesiran resulted in a significant reduction of 24-hour ambulatory systolic blood pressure (SBP) at 12 weeks (MD -11.90; 95% CI: -13.42, -10.38; p-value <0.00001) and 24 weeks (MD -9.05; 95% CI: -10.37, -7.73; p-value <0.00001). Mean office SBP was also significantly lowered at 12 weeks (MD -10.68; 95% CI: -12.21, -9.14; p-value <0.00001) and 24 weeks (MD -8.49; 95% CI: -9.70, -7.28; p-value <0.00001). Meaningful reductions in 24-hour ambulatory diastolic blood pressure (DBP) were observed at 12 weeks (MD -8.67; 95% CI: -9.89, -7.47; p-value <0.00001) and 24 weeks (MD -7.90; 95% CI: -9.12, -6.68; p-value <0.00001). Zilebesiran was associated with a modest increase in total adverse events (OR 1.37; 95% CI: 1.06, 1.76; p-value =0.01), but showed no significant difference in severe adverse events compared to placebo (OR 0.75; 95% CI: 0.36, 1.57; p-value =0.45). Changes in serum creatinine (SMD -0.01; 95% CI: -0.16, 0.13; p-value =0.20) and eGFR (estimated glomerular filtration rate) levels (SMD -0.06; 95% CI: -0.21, 0.08; p-value =0.39) were also not statistically significant. This meta-analysis confirms that Zilebesiran is consistently associated with significant reductions in both ambulatory and office blood pressure over 12 to 24 weeks, with an acceptable safety profile. Further trials are needed to evaluate the efficacy, dosing, and safety outcomes of Zilebesiran across diverse hypertensive populations.

01 Aug 2025·British Journal of Pharmacology

Advancing antihypertensive drug development

Review

Author: Zhang, Hongyuan ; Green, Darren ; Wang, Xin ; Ahmed, Fozia Zahir ; Liu, Yanrong ; Pu, Fay

Hypertension affects more than a billion individuals worldwide and remains a major cause of cardiovascular morbidity and mortality. Despite advances in therapies, optimal blood pressure control remains elusive for many patients because of treatment resistance, adverse effects, and adherence challenges. This review highlights innovative approaches in hypertension management. Aldosterone synthase inhibitors (ASIs) and non‐steroidal mineralocorticoid receptor antagonists improve blood pressure control and offer cardiorenal benefits while reducing adverse effects including hyperkalaemia. Endothelin receptor antagonists show promise in resistant hypertension by addressing vasoconstrictive pathways. RNA‐based therapies, like zilebesiran, provide a novel approach to suppress angiotensinogen, offering durable antihypertensive effects with less frequent dosing. Additional advances include AT2 receptor agonists, ACE2/Angiotensin‐(1–7)/MAS receptor activators and NAD+ boosting compounds, which target key mechanisms of vascular dysfunction and ageing‐related hypertension. Gut microbiome‐targeted therapies and fixed‐dose combination pills are also discussed for their potential to enhance blood pressure control and patient adherence. These emerging therapies not only aim to lower blood pressure but also address underlying pathophysiological mechanisms, offering a precision‐focussed approach to treatment. By critically analysing these developments, this review provides insights into how novel strategies can overcome existing challenges in hypertension management, reduce the global disease burden and improve patient outcomes.

01 Jul 2025·JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension

Article

Importance:

In prior monotherapy studies of patients with hypertension, single subcutaneous doses of zilebesiran, an investigational RNA interference therapeutic, reduced serum angiotensinogen levels and systolic blood pressure (SBP) at 3 and 6 months.

Objective:

To evaluate the efficacy and safety of zilebesiran vs placebo when added to a standard antihypertensive medication.

Design, Setting, and Participants:

This phase 2, randomized, prospective, double-blinded trial enrolled adults with uncontrolled hypertension from 150 sites across 8 countries between January 2022 and June 2023. The final follow-up date was December 11, 2023, and analyses were conducted on March 1, 2024.

Interventions:

Eligible patients were initially randomized in cohorts to receive open-label run-in treatment for at least 4 weeks with indapamide 2.5 mg, amlodipine 5 mg, or olmesartan 40 mg (4:7:10 randomization), each administered once daily. Within cohorts, adherent patients with 24-hour mean ambulatory SBP of 130 mm Hg to 160 mm Hg were subsequently randomized (1:1) to additional blinded treatment to receive single subcutaneous doses of zilebesiran 600 mg or matching placebo.

Main Outcomes and Measures:

The primary end point in each cohort was the difference between zilebesiran and placebo in change from baseline in 24-hour mean ambulatory SBP at 3 months.

Results:

Of 1491 patients entering the run-in phase, 663 (130 receiving indapamide, 240 receiving amlodipine, and 293 receiving olmesartan) were randomized to receive zilebesiran (n = 332) or placebo (n = 331). The least-squares mean difference between zilebesiran and placebo in change from baseline to 3 months in 24-hour mean ambulatory SBP was −12.1 mm Hg (95% CI, −16.5 to −7.6; P &lt; .001) for indapamide, −9.7 mm Hg (95% CI, −12.9 to −6.6; P &lt; .001) for amlodipine, and −4.5 mm Hg (95% CI, −8.2 to −0.8; P = .02) for olmesartan. Across cohorts, more patients who received zilebesiran than placebo experienced hyperkalemia (18 [5.5%] vs 6 [1.8%]), hypotension (14 [4.3%] vs 7 [2.1%]), and acute kidney failure (16 [4.9%] vs 5 [1.5%]) events, but most episodes were mild and resolved without medical intervention.

Conclusions and Relevance:

In patients with uncontrolled hypertension despite treatment with indapamide, amlodipine, or olmesartan, the addition of single-dose zilebesiran resulted in significant SBP reductions compared with placebo at 3 months, with low rates of serious adverse events.

Trial Registration:

ClinicalTrials.gov Identifier: NCT05103332

News (Medical) associated with Zilebesiran

17 Dec 2025

·www.fiercepharma.com

Alnylam lays out $250M to equip flagship facility with cutting-edge siRNA production tech

Alnylam Pharmaceuticals plans to spend $250 million in a bid to elevate its 200,000-square-foot facility in Norton, Massachusetts. With demand for its RNA interference meds booming, Alnylam Pharmaceuticals has commenced work to soup up its flagship manufacturing facility in Massachusetts.Alnylam plans to spend $250 million in a bid to elevate its 200,000-square-foot facility in Norton, Massachusetts, as the biopharma industry’s first fully dedicated small interfering RNA (siRNA) enzymatic-ligation production plant, the Cambridge-based company said Dec. 17.The project is expected to bolster capacity and reduce operating costs at the facility, which officially opened its doors for siRNA oligonucleotide bulk drug substance active pharmaceutical ingredient manufacturing back in 2021, according to Alnylam’s website. Online, Alnylam refers to the Norton site as its global production HQ.Meanwhile, the enzymatic ligation tech at the heart of the undertaking is expected to buoy the launch of future Alnylam meds as the company increasingly aims its development engine at more widespread conditions. The project revolves around siRELIS, Alnylam’s next-generation, scalable enzymatic ligation platform. The company contends that the platform builds RNAi therapeutics more efficiently by curbing material and plant resource requirements. The tech has the potential to “greatly” expand manufacturing capacity, which Alnylam argues makes “large-scale, sustainable production possible.”In terms of how it works, the siRELIS (siRNA Enzymatic Ligation Synthesis) platform assembles short, high-quality RNA fragments—which Alnylam has dubbed “blockmers”—into complete molecules, under a process the company asserts is more efficient than traditional siRNA production methods.The historic process for producing RNAi and other genetic medicines drug substance requires joining modified nucleosides to form sequences of nucleotides that make up the desired siRNA, Alnylam explained in a recent YouTube video. While effective, this process can take days and is inefficient for programs requiring larger amounts of drug substance or longer siRNA strands, the company pointed out.SiRELIS, by contrast, synthesizes preformed nucleotide sequences that are then stitched together using enzymes.Meanwhile, the FDA has also recognized the platform in its Emerging Technology Program, Alnylam noted in its announcement. SiRELIS has earned the distinction following the successful demonstration of Alnylam’s enzymatic ligation approach via pilot-scale batches of the experimental drugs zilebesiran, under development to reduce the risk of major cardiovascular events in patients with high blood pressure, and nucresiran, in development for transthyretin-mediated amyloidosis (ATTR), the company said.“At this pivotal time with our expanding pipeline of RNAi therapeutics, Alnylam is accelerating development of siRNA manufacturing and changing what’s possible in a single facility,” Yvonne Greenstreet, M.D., Alnylam’s chief executive, said in a statement. “This advance will be a critical enabler in the scaling of our pipeline to include potential treatments for diseases such as hypertension, type 2 diabetes, and obesity.”The expansion at the Norton plant is slated to boost both clinical and commercial supply of Alnylam’s siRNA oligonucleotide drug substance and will be used for supply of medications outside of the U.S. as well, the company noted in Wednesday’s release.The drugmaker has already started construction on the project, with the expectation that the new capabilities will come online at the plant by late 2027. The expansion is also set to add an unspecified number of new jobs.Alnylam has been on a hot streak this year, spurred on in no small part by the success of its rare heart disease drug Amvuttra, which was first approved in ATTR-polyneuropathy (ATTR-PN) in 2022 and picked up a key second green light in ATTR-cardiomyopathy (ATTR-CM) this past March.Back in August, that performance was strong enough to lift Alnylam’s market cap above $50 billion, where it still stands today. And, as of October, Amvuttra was still managing to eclipse Wall Street expectations. In the third quarter, Alnylam’s ATTR drug generated $685 million in sales, coming in 11% above analyst consensus estimates, according to a note from Jefferies at the time.For the full year, Alnylam is now expecting total transthyretin amyloidosis franchise revenues to land between $2.475 billion and $2.525 billion.

OligonucleotideDrug Approval

17 Dec 2025

·firstwordpharma.com

Alnylam pours $250M to expand RNAi manufacturing in Massachusetts

A $250-million manufacturing outlay will see Alnylam Pharmaceuticals expand its US operations while moving toward a new, more efficient way of making RNAi drugs. The company is adding an enzymatic ligation platform to its facility in Norton, Massachusetts, creating what it expects will be industry's first fully dedicated site for this type of siRNA production."Manufacturing oligonucleotide-based medicines is highly complex, and the current manufacturing technology will struggle to meet increased demand," said Timothy Maines, chief technical operations and quality officer at Alnylam, in a release Wednesday. "We have successfully applied a reproducible, less time-intensive process that increases throughput while maintaining the highest quality standards."At the centre of the investment is Alnylam's siRELIS platform, which has been accepted into the FDA's Emerging Technology Program, giving the company a channel to engage earlier with the US regulator about its new process.Unlike traditional synthesis, where RNA strands are built one nucleotide at a time, siRELIS synthesises nucleotide sequences – known as "blockmers" – and stitches them together using enzymes to form duplex siRNA. "Like modular home construction, Alnylam's enzymatic-ligation approach builds medicines from premade assembled parts, an important step towards advancing how oligonucleotide-based medicines like RNAi therapeutics are made," the company explains in a short video about the technology.Alnylam has already used enzymatic ligation to produce pilot-scale batches of zilebesiran, which is being studied to reduce the risk of major adverse cardiovascular events in hypertension patients, and nucresiran, a therapy it is developing for transthyretin-mediated amyloidosis. "This advance will be a critical enabler in the scaling of our pipeline to include potential treatments for diseases such as hypertension, type 2 diabetes and obesity," said CEO Yvonne Greenstreet.The Norton expansion, which is expected to be operational by late 2027, comes amid a broader resurgence of US pharmaceutical manufacturing investment, as drugmakers pour tens of billions of dollars into domestic plants and research hubs. Companies including Merck & Co., Roche and AstraZeneca, among a slew of others, have announced large US capital programmes over the past year, a trend that has accelerated under the Trump administration, which has been pressing industry to reshore production.

Oligonucleotide

17 Dec 2025

·investors.alnylam.com

Alnylam to Invest $250 Million to Add Enzymatic Ligation Platform to U.S. Manufacturing Facility to Meet Growing Global Demand for RNAi Therapeutics

Dec 17, 2025 New platform is expected to substantially increase manufacturing capacity and lower production costs, enabling investment in expanding pipeline FDA has accepted Alnylam’s enzymatic ligation manufacturing platform into its Emerging Technology Program, fast-tracking global regulatory engagement CAMBRIDGE, Mass. --(BUSINESS WIRE)--Dec. 17, 2025-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced the planned expansion of its state-of-the-art manufacturing facility in Norton, Massachusetts . The Company is preparing to invest $250 million to advance what is poised to become the industry’s first fully dedicated, proprietary, siRNA enzymatic-ligation manufacturing facility. This investment is expected to meaningfully expand capacity, significantly reduce production costs, and position Alnylam to support future launches across its growing pipeline of potential new medicines. As part of the expansion, Alnylam also announced that this next-generation, scalable, enzymatic ligation manufacturing platform, siRELIS™, has been accepted into the U.S. Food and Drug Administration’s (FDA) Emerging Technology Program, accelerating dialogue with global health authorities on innovative manufacturing approaches for oligonucleotide-based medicines. This acceptance follows successful demonstration of Alnylam’s enzymatic ligation platform through production of pilot-scale batches of zilebesiran, which is being studied to reduce the risk of major adverse cardiovascular events in patients with hypertension (high blood pressure), and nucresiran, which is in development for the treatment of transthyretin-mediated amyloidosis (ATTR). “At this pivotal time with our expanding pipeline of RNAi therapeutics, Alnylam is accelerating development of siRNA manufacturing and changing what’s possible in a single facility,” said Yvonne Greenstreet , M.D., MBA, Chief Executive Officer of Alnylam . “This advance will be a critical enabler in the scaling of our pipeline to include potential treatments for diseases such as hypertension, type 2 diabetes, and obesity.” Expansion in Norton, MA The $250 million expansion of Alnylam’s 200,000 sq. ft. Norton facility will increase its capabilities to locally produce both clinical and commercial supply of siRNA oligonucleotide drug substance for patients around the world. The facility, which opened in 2021, has played a key role in the growth of Alnylam’s clinical pipeline and acts as a pipeline accelerator for early-stage programs, including programs targeting different tissue types (e.g., liver, CNS, muscle, adipose, etc.). This expansion will strengthen Massachusetts’ position as a global hub of life sciences innovation. Construction is underway, with new capabilities expected to become fully operational by late 2027. “Alnylam represents the world-class health care innovation Massachusetts is known for. Alnylam has been a leader in life sciences in our state for over two decades,” said Governor Maura Healey . “Their scientific breakthroughs in siRNA manufacturing have transformed care by providing RNAi therapeutics to people who need it most, while creating thousands of jobs across our state. We're excited to support their growth through the expansion of a manufacturing facility in Southeastern Mass., and we're grateful for their continued investment in Massachusetts.” “Alnylam’s continued investment in Massachusetts underscores the Commonwealth’s role as a global leader in biomanufacturing,” said Dr. Kirk Taylor , President and CEO of the Massachusetts Life Sciences Center (MLSC). “This expansion will bring high-quality jobs to this area and ensure patients worldwide have the opportunity to benefit from medicines made right here in Massachusetts . We look forward to deepening our partnership as we work together to advance the thriving life sciences ecosystem here in the Commonwealth.” A Breakthrough in Manufacturing at Scale Alnylam’s siRELIS™ platform builds RNAi therapeutics more efficiently using fewer materials and plant resources, and greatly expands capacity – making large-scale, sustainable production possible. “Manufacturing oligonucleotide-based medicines is highly complex, and the current manufacturing technology will struggle to meet increased demand. We have successfully applied a reproducible, less time-intensive process that increases throughput while maintaining the highest quality standards,” said Timothy Maines , Chief Technical Operations and Quality Officer at Alnylam . “The expansion of our Norton facility presents an opportunity to reinvent what’s possible in oligonucleotide manufacturing.” About Enzymatic Ligation Alnylam’s siRELIS™ (siRNA Enzymatic Ligation Synthesis) platform is a next-generation approach to siRNA manufacturing that assembles short, high-quality RNA fragments called “blockmers” into complete molecules more efficiently than traditional methods. This scalable, sustainable platform reduces use of starting materials and reliance on organic solvents and plant time, increasing capacity in a single facility. A brief video about enzymatic ligation can be viewed here. About Alnylam Manufacturing Alnylam has pioneered small interfering RNA (siRNA) manufacturing at scale, building world-class capabilities in chemistry, engineering, and quality. With a legacy of firsts and a commitment to speed, safety, and sustainability, Alnylam delivers innovative RNAi therapeutics to patients worldwide. To learn more, please visit the “Making Our Medicines” page on Alnylam’s website. About RNAi Therapeutics 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. 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. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. 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. 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 include AMVUTTRA® (vutrisiran), ONPATTRO® (patisiran), GIVLAARI® (givosiran), and OXLUMO® (lumasiran), which are being developed and commercialized by Alnylam , and Leqvio® (inclisiran) and Qfitlia™ (fitusiran), which are being developed and commercialized by Alnylam’s partners, Novartis and Sanofi, respectively. 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 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. Forward Looking Statements 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, statements regarding the planned expansion of Alnylam’s manufacturing facility in Norton, Massachusetts , including Alnylam’s planned $250 million investment in the expansion; the ability of Alnylam’s Norton, Massachusetts facility to meet the global demand for Alnylam’s RNAi therapeutics; Alnylam’s ability to advance the industry’s first fully dedicated, proprietary, siRNA enzymatic-ligation manufacturing facility; the potential for Alnylam’s enzymatic ligation based manufacturing platform to expand manufacturing capacity, reduce production costs, enable more efficient production of RNAi therapeutics, make large-scale, sustainable production possible, and position Alnylam to invest in its pipeline and support future launches; Alnylam’s ability to accelerate development of siRNA manufacturing and to change what’s possible in a single facility; the potential for enzymatic ligation to be a critical enabler in the scaling of Alnylam’s portfolio to include potential treatments for diseases such as hypertension, type 2 diabetes and obesity; the potential for the expansion of Alnylam’s Norton facility to increase its capabilities to locally produce both clinical and commercial supply of siRNA oligonucleotide drug substance; the potential for Alnylam’s new manufacturing capabilities to become fully operational by late 2027; the potential for the expansion of Alnylam’s Norton facility to bring high quality jobs to the area and to ensure that patients worldwide have the opportunity to benefit from medicines made in Massachusetts ; and the potential for the expansion of Alnylam’s Norton facility to reinvent what’s possible in oligonucleotide manufacturing 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 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, including Roche, Novartis, Sanofi, and Regeneron; the outcome of litigation; the risk of future government investigations; and unexpected expenditures; as well as those risks and uncertainties more fully discussed in the “Risk Factors” filed with Alnylam’s 2024 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC . In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements. View source version on businesswire.com: https://www.businesswire.com/news/home/20251217194595/en/ Alnylam Pharmaceuticals, Inc. Christine Akinc (Investors and Media) +1-617-682-4340 Josh Brodsky (Investors) +1-617-551-8276 Source: Alnylam Pharmaceuticals, Inc.

Oligonucleotide

100 Deals associated with Zilebesiran

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 3	United States	Alnylam Pharmaceuticals, Inc.	22 Sep 2025
Alzheimer Disease	Phase 1	United States	Alnylam Pharmaceuticals, Inc.	31 Dec 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06272487 (KARDIA-3, NEWS) Manual	Phase 2	Hypertension	270	Zilebesiran 300 mg	xmbjsdhpkn(qfbvuqqjkq) = bvgfaanhou gvztuqjntn (jtnxsfjgaf, -9.9 to -0.2) View more	Negative	30 Aug 2025
				Zilebesiran 600 mg	xmbjsdhpkn(qfbvuqqjkq) = olftmzyjgu gvztuqjntn (jtnxsfjgaf, -8.2 to 1.6) View more
NCT05103332 (KARDIA-2, Corporate Publications) Manual	Phase 2	Hypertension	672	Indapamide 2.5 mg+Zilebesiran	bvgqzywfem(elydrzdala) = gludwjpkjb emnqhfuvrr (tyhvrrsdef ) Met View more	Positive	07 Apr 2024
				Indapamide 2.5 mg+Placebo	extwjtnkdq(makyovwuid) = ogmbuxqqfz pmyoyiylek (phromnyugi ) View more
NCT04936035 (Pubmed) Manual	Phase 2	Hypertension	394	zilebesiran (150 mg once every 6 months)	lbzvlmzvmo(jxpgvlzvaf) = emmratbnwi vbqirxuved (vnouqkypsc, -10.3 to -4.4)	Positive	05 Mar 2024
				zilebesiran (300 mg once every 6 months)	lbzvlmzvmo(jxpgvlzvaf) = niwkuqqjft vbqirxuved (vnouqkypsc, -12.0 to -7.9)
NCT05103332 (KARDIA-2, Corporate Publications) Manual	Phase 2	Hypertension	672	Zilebesiran+Standard of Care Antihypertensives	gnnqvtakbe(syvehzinuq) = Study Met the Primary Endpoint Demonstrating Clinically Significant Systolic Blood Pressure Reductions at Month 3 When Zilebesiran Was Added to a Diuretic, Calcium-Channel Blocker or Angiotensin Receptor Blocker fdnquynhdv (vejvirqqex ) Met	Positive	05 Mar 2024
				placebo+Standard of Care Antihypertensives
NCT04936035 (KARDIA-1, PipelineReview) Manual	Phase 2	Hypertension	394	zilebesiran	ngqvqinmll(xebdhmvpzz) = akchdxxfge pxisciqqhi (csnionhxlq ) View more	Positive	13 Nov 2023
				zilebesiran	ngqvqinmll(xebdhmvpzz) = bjlqpoumyn pxisciqqhi (csnionhxlq ) View more
NCT04936035 (KARDIA-1, AHA2023) Manual	Phase 2	Hypertension	377	Zilebesiran	fbfhrxskye(wivausnypu) = Reductions from baseline in 24-hour mean SBP were significantly greater for all zilebesiran regimens than placebo at Month 3 and Month 6 (p<0.0001, all comparisons), with consistent reductions in daytime and nighttime SBP. mvjywkgwjv (saqrfxmtpc ) View more	Positive	11 Nov 2023
				Placebo
NCT03934307 (Corporate Publications) Manual	Phase 1	Hypertension	112	zilebesiran	omsszdanob(sybmiwqhjc) = oixyubwevw wfrdevzmny (pavtbrudej )	Positive	19 Jul 2023
				placebo	omsszdanob(sybmiwqhjc) = ofrvqbysrt wfrdevzmny (pavtbrudej )
ALN-AGT (ESH2021)	Phase 1	Hypertension angiotensinogen	-	ALN-AGT	dnrlqsygpb(dvlzsosejg) = axnlllqrzu mqkwwliaub (vnkjabfgwf ) View more	Positive	01 Apr 2021

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