Alnylam Highlights New Cardiovascular Data at ACC.26, Reinforcing Potential of RNAi Therapies in ATTR-CM and Hypertension
Alnylam Pharmaceuticals has unveiled a comprehensive set of new clinical and real-world findings from its cardiovascular portfolio at the American College of Cardiology Annual Scientific Session and Expo 2026, further strengthening the case for RNA interference (RNAi) as a transformative approach in the treatment of cardiovascular disease (CVD). The data presented span both approved and investigational therapies, including vutrisiran and zilebesiran, highlighting meaningful progress in addressing conditions such as transthyretin amyloidosis and hypertension.
The company’s latest results underscore the potential of RNAi-based therapies to deliver durable, targeted, and clinically meaningful benefits by addressing disease at its genetic source. With growing clinical evidence and expanding real-world experience, Alnylam continues to position its cardiovascular pipeline as a key driver of innovation in precision medicine.
Vutrisiran Strengthens Position in ATTR-CM Treatment
A major focus of the presentations was vutrisiran, the first and only therapy designed to silence transthyretin (TTR) production at its source. Vutrisiran is approved for the treatment of both cardiomyopathy and polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (ATTR), a progressive and often fatal condition caused by the buildup of misfolded TTR protein.
New analyses from the Phase 3 HELIOS-B study further reinforce the potential of vutrisiran as a first-line therapy for patients with ATTR cardiomyopathy (ATTR-CM), including both wild-type and hereditary forms of the disease. The data demonstrate that treatment with vutrisiran leads to meaningful and sustained improvements in how patients feel and function, with benefits observed across a broad range of disease severities.
Importantly, these improvements are not limited to clinical endpoints alone but extend to health-related quality of life (QoL), a critical consideration for patients living with chronic and debilitating cardiovascular conditions.
Quality-of-Life Improvements Demonstrated in HELIOS-B
One of the key analyses presented evaluated patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), a widely used tool for assessing QoL in heart failure patients. Over a 30-month period, patients treated with vutrisiran demonstrated improvements across nearly all components of the questionnaire compared to placebo.
The most pronounced benefits were seen in physical limitations and overall quality of life, suggesting that TTR silencing translates into tangible improvements in daily functioning. Notably, the magnitude of the treatment effect was comparable to the difference typically observed between patients more than a decade apart in age, highlighting the clinical relevance of these findings.
These results, which were also published in the European Journal of Heart Failure, provide robust evidence supporting the long-term benefits of vutrisiran in improving patient well-being.
Reduced Disease Progression and Improved Outcomes in Advanced Patients
Additional post hoc analyses from HELIOS-B examined the impact of vutrisiran on disease progression and outcomes in patients with more advanced ATTR-CM. The findings indicate that fewer patients receiving vutrisiran progressed to advanced disease stages compared to those on placebo.
Among patients who did progress, treatment with vutrisiran was associated with significant reductions in the risk of adverse outcomes. Specifically, the therapy reduced the risk of all-cause mortality and recurrent cardiovascular events by up to 40% in the overall population and 46% in patients receiving vutrisiran as monotherapy.
Furthermore, extended follow-up data showed reductions in all-cause mortality of up to 56% in the overall population and 77% in the monotherapy group, compared to placebo. These findings are particularly important for high-risk patients, as they suggest that vutrisiran may not only delay disease progression but also improve survival outcomes.
Benefits Across Diastolic Dysfunction Severity
Another analysis explored the effects of vutrisiran across different levels of diastolic dysfunction, a key prognostic factor in ATTR-CM. Patients with higher baseline severity typically face worse outcomes, making effective treatment particularly critical.
The data showed that vutrisiran reduced the risk of worsening diastolic dysfunction and was associated with a greater proportion of patients maintaining or improving their New York Heart Association (NYHA) functional class over time. These benefits were observed regardless of baseline severity, indicating that vutrisiran may provide consistent efficacy across diverse patient populations.
Real-World Evidence Confirms High Adherence
Beyond clinical trials, Alnylam also presented real-world data demonstrating strong adherence and persistence among patients treated with vutrisiran. In a retrospective cohort study, more than 93% of patients maintained high adherence, defined as a proportion of days covered (PDC) of at least 0.8.
Patients were followed for an average of over 600 days, with most continuing treatment beyond 12 months. This high level of adherence is likely supported by the therapy’s convenient dosing schedule, which involves just four healthcare provider-administered doses per year.
The growing body of real-world evidence, combined with more than 13,000 patient-years of experience across indications, further supports the safety, tolerability, and practicality of vutrisiran in routine clinical use.
Zilebesiran Advances as a Novel Hypertension Therapy
In addition to vutrisiran, Alnylam highlighted progress with zilebesiran, an investigational RNAi therapeutic aimed at reducing cardiovascular risk in patients with hypertension.
Zilebesiran works by targeting angiotensinogen (AGT), the upstream precursor in the renin-angiotensin-aldosterone system (RAAS), a key regulator of blood pressure. By inhibiting AGT production in the liver, zilebesiran has the potential to provide sustained blood pressure control with infrequent dosing, potentially as little as twice per year.
Data from pooled Phase 2 studies in the KARDIA program demonstrated a favorable safety profile across a range of patient populations, including those with mild-to-moderate hypertension, high cardiovascular risk, and reduced kidney function.
Favorable Safety Profile Supports Continued Development
The safety analysis showed that clinically relevant adverse events, such as hypotension, hyperkalemia, and declines in estimated glomerular filtration rate (eGFR), were infrequent across all study groups. These findings held true even when zilebesiran was used in combination with standard-of-care antihypertensive therapies, including ACE inhibitors and angiotensin receptor blockers.
Most adverse events were transient and resolved without intervention, supporting the overall tolerability of the therapy. These results provide a strong rationale for continued evaluation in the ongoing Phase 3 ZENITH cardiovascular outcomes trial, which was initiated in September 2025.
The ZENITH study is designed to assess the long-term impact of zilebesiran on cardiovascular outcomes in patients with hypertension who remain at high risk despite standard treatment.
Safety Considerations for Vutrisiran
As with any therapy, safety considerations remain an important component of clinical use. Treatment with vutrisiran is associated with reduced serum vitamin A levels, and patients are advised to take supplementation at recommended daily allowance levels.
Common adverse reactions observed in clinical studies include pain in extremities, joint pain, shortness of breath, and decreased vitamin A levels. Importantly, no new safety concerns were identified in patients with ATTR-CM, further reinforcing the therapy’s established safety profile.
Patients experiencing symptoms suggestive of vitamin A deficiency, such as night blindness, are advised to seek evaluation by an ophthalmologist.
The data presented at ACC.26 highlight the growing impact of RNAi therapeutics in cardiovascular medicine. By targeting disease at its genetic origin, therapies like vutrisiran and zilebesiran offer a fundamentally different approach compared to traditional treatments.
For patients with ATTR-CM, vutrisiran continues to demonstrate meaningful clinical benefits, including improved quality of life, reduced disease progression, and enhanced survival outcomes. Meanwhile, zilebesiran represents a promising new option for managing hypertension, with the potential to simplify treatment and improve adherence.
As Alnylam advances its pipeline through late-stage clinical development and real-world implementation, the company remains at the forefront of RNAi innovation, with the potential to redefine standards of care across multiple cardiovascular indications.
Alnylam’s latest presentations reinforce the promise of RNAi therapeutics as a powerful tool in the fight against cardiovascular disease. With strong clinical data, real-world validation, and a robust development pipeline, the company is well positioned to deliver next-generation therapies that address critical unmet needs and improve patient outcomes on a global scale.
About AMVUTTRA ® (vutrisiran)
AMVUTTRA ® (vutrisiran) is a transthyretin (TTR) silencer that delivers rapid knockdown of TTR at the source to address the underlying cause of transthyretin amyloidosis (ATTR). In a clinical study, AMVUTTRA rapidly knocked down TTR in as early as six weeks and decreased TTR levels by 87% with two and a half years of treatment. It is approved as a treatment for the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults and for the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults in various countries, globally. Administered quarterly via subcutaneous injection, AMVUTTRA is the first and only silencer approved for the treatment of ATTR-CM and hATTR-PN.
About Transthyretin Amyloidosis (ATTR)
Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by pathogenic 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. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant. It is estimated that more than 500,000 people worldwide live with ATTR.
About Zilebesiran
Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic in development for cardiovascular (CV) risk reduction in patients with hypertension. Zilebesiran targets angiotensinogen (AGT), the most upstream precursor in the renin-angiotensin-aldosterone system (RAAS), which plays a role in blood pressure (BP) regulation and impacts CV and renal health. Clinical trial results have shown the potential for zilebesiran to provide continuous control of BP with biannual dosing in a broad population of patients with hypertension. 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.
About Cardiovascular Disease and Hypertension
Cardiovascular disease (CVD) is a global health crisis and a leading cause of death worldwide, responsible for approximately 20 million deaths annually. Hypertension is the primary cause of and number one modifiable risk factor for CVD. An estimated one in three adults worldwide have hypertension, and despite wide availability of antihypertensives, up to 80% of all patients, and up to one-third of treated patients, do not reach and maintain blood pressure (BP) targets. Even when BP appears well-managed, continuous control of BP may remain suboptimal, leading to variability in BP during the 24-hour period, and in the long-term, putting patients at greater risk of cardiovascular events and end organ damage.
About 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. 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 genetics and other diseases.
About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is a leading global biopharmaceutical company and the pioneer of the RNA interference (RNAi) revolution. The Company is focused on developing transformative therapies with the potential to prevent, halt, or reverse disease. For more than two decades, Alnylam has advanced the Nobel-Prize-winning science of RNAi, delivering critical breakthroughs and six approved medicines. Alnylam has medicines available in more than 70 countries and a rapidly expanding and robust pipeline, in addition to consistently being recognized as an exceptional workplace and socially responsible organization. The Company is executing on its Alnylam 2030 strategy to accelerate innovation and scale impact to transform human health.
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