New Heart Failure 2026 Analyses Highlight Consistent Clinical Benefits of Vutrisiran Across Diverse ATTR-CM Patient Groups
Alnylam Pharmaceuticals has announced new analyses from its Phase 3 HELIOS-B clinical trial evaluating vutrisiran in patients with transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM), providing additional evidence supporting the therapy’s durability, clinical consistency, and established safety profile across a broad range of patient populations commonly encountered in real-world medical practice.
The findings were presented during Heart Failure 2026, the annual scientific congress organized by the Heart Failure Association of the European Society of Cardiology. According to Alnylam, the newly reported analyses further reinforce the potential role of vutrisiran as a first-line treatment option for patients living with ATTR-CM, a progressive and potentially fatal disease affecting the heart.
Vutrisiran is currently the first and only transthyretin (TTR) silencing therapy approved for ATTR-CM that is specifically designed to rapidly reduce production of transthyretin protein at its source in the liver. The therapy utilizes RNA interference (RNAi) technology, a gene-silencing approach that targets messenger RNA responsible for producing disease-causing proteins.
ATTR amyloidosis is a rare and serious disease caused by the misfolding and accumulation of transthyretin protein in various tissues throughout the body. In ATTR-CM, abnormal amyloid deposits accumulate in the heart muscle, leading to stiffening of the heart, progressive heart failure, arrhythmias, reduced functional capacity, and ultimately shortened survival.
The disease exists in two primary forms: hereditary ATTR amyloidosis, caused by inherited mutations in the TTR gene, and wild-type ATTR amyloidosis, which develops without inherited mutations and is more commonly associated with aging. Both forms can significantly impair cardiac function and quality of life.
The HELIOS-B study was designed to evaluate the efficacy and safety of vutrisiran in patients with both hereditary and wild-type ATTR-CM. The new analyses presented at Heart Failure 2026 focused on clinically complex patient populations that are frequently seen in everyday cardiology practice, including patients with atrial fibrillation, low systolic blood pressure, high comorbidity burden, and those already receiving background therapies such as transthyretin stabilizers and heart failure medications.
Scott Solomon, Professor of Medicine at Harvard Medical School and cardiologist at Brigham and Women’s Hospital, said the analyses provide important insight into how vutrisiran performs across the diverse patient populations physicians encounter in routine clinical care.
According to Solomon, the results demonstrated that the clinical benefits associated with vutrisiran were maintained even among patients with advanced or clinically challenging disease characteristics. These included patients with atrial fibrillation, low systolic blood pressure, and multiple coexisting medical conditions.
He noted that the therapy also showed consistent treatment effects in patients already receiving standard-of-care therapies, including TTR stabilizers such as tafamidis and disease-modifying heart failure treatments. Solomon emphasized that the consistency of the treatment effect across multiple patient subgroups supports the relevance of vutrisiran in real-world practice and strengthens the case for its use as a first-line therapy for ATTR-CM.
One of the most significant findings involved patients with atrial fibrillation, a common cardiac arrhythmia frequently associated with more advanced ATTR-CM disease. Approximately 65% of patients enrolled in the HELIOS-B study had atrial fibrillation at baseline.
In this subgroup, treatment with vutrisiran significantly reduced the combined risk of all-cause mortality and recurrent cardiovascular events compared with placebo. The findings are considered particularly important because patients with atrial fibrillation often experience more severe disease progression and face elevated risks of hospitalization, stroke, worsening heart failure, and mortality.
The analyses also evaluated patients with low systolic blood pressure, another high-risk subgroup often associated with advanced heart failure and poor prognosis. According to the data presented, vutrisiran slowed the progressive decline in systolic blood pressure observed over time in these patients, suggesting potential stabilization of cardiovascular function despite disease severity.
Researchers further reported that the therapy’s clinical benefits remained consistent regardless of patients’ overall comorbidity burden. ATTR-CM patients frequently present with multiple overlapping health conditions, including hypertension, kidney disease, diabetes, coronary artery disease, and arrhythmias, which can complicate treatment decisions and affect outcomes.
Importantly, vutrisiran demonstrated consistent efficacy even among patients receiving concomitant disease-modifying therapies. These included transthyretin stabilizers such as tafamidis, as well as commonly used heart failure medications including sodium-glucose cotransporter-2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRAs), beta blockers, and angiotensin-converting enzyme inhibitor or angiotensin receptor-neprilysin inhibitor therapies.
The consistency observed across these treatment combinations suggests that vutrisiran may be integrated into existing treatment regimens without compromising efficacy. This flexibility could prove important as clinicians increasingly adopt multidrug treatment approaches for managing ATTR-CM and associated cardiovascular complications.
The analyses also highlighted consistent treatment effects among women enrolled in the HELIOS-B trial. Female patients have historically been underrepresented in ATTR-CM clinical studies, creating gaps in understanding regarding disease presentation and therapeutic response in women.
By demonstrating similar benefits across male and female patient populations, the findings help address an important area of unmet clinical evidence and support broader applicability of the therapy across diverse patient groups.
In addition to efficacy findings, Alnylam presented a large pooled safety analysis examining the relationship between transthyretin-lowering RNAi therapies and adverse events potentially associated with vitamin A deficiency.
Transthyretin plays a role in transporting vitamin A throughout the body, leading researchers and clinicians to monitor whether therapies that lower TTR protein levels could potentially contribute to vitamin A-related complications. Patients treated with RNAi therapies such as vutrisiran and patisiran are generally advised to take vitamin A supplementation at recommended daily levels.
The pooled analysis included more than 25,000 patient-years of treatment exposure across vutrisiran and patisiran clinical development programs and post-marketing safety data, making it one of the largest safety evaluations conducted for TTR-lowering RNAi therapies.
According to the analysis, rates of ocular adverse events potentially associated with vitamin A deficiency were low and comparable to placebo-treated patients. Investigators also reported that no cases of clinically meaningful vitamin A deficiency were observed.
William S. Blaner, Professor of Nutritional Medicine at Columbia University and an expert in vitamin A metabolism and transport, explained that although transthyretin contributes to vitamin A transport, multiple physiologic pathways support delivery of vitamin A throughout the body.
Blaner stated that the low incidence of vitamin A deficiency-related adverse events observed in the analysis provides strong reassurance that lowering transthyretin levels does not appear to meaningfully increase the risk of clinically significant vitamin A deficiency in patients with ATTR amyloidosis.
The safety findings are particularly relevant as clinicians and regulators continue evaluating the long-term effects of TTR-lowering therapies, especially in chronic diseases requiring extended treatment durations.
Beyond the HELIOS-B analyses, Alnylam also presented details regarding the design and rationale of a new global observational study known as DemonsTTRate. The prospective study is intended to evaluate real-world outcomes in patients with ATTR-CM across routine clinical practice settings.
The DemonsTTRate study is expected to enroll more than 2,000 patients globally and follow participants for up to five years. Researchers plan to collect longitudinal data on clinical outcomes, treatment patterns, healthcare resource utilization, disease progression, and patient management strategies.
Observational studies such as DemonsTTRate are becoming increasingly important in rare disease research because they provide insight into how therapies perform outside controlled clinical trial settings. Real-world evidence can help clinicians better understand long-term treatment effectiveness, patient adherence, healthcare utilization patterns, and disease management challenges across broader patient populations.
Alnylam noted that global experience with vutrisiran across ATTR-CM and hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) now exceeds 13,000 patient-years of exposure. This growing body of clinical and real-world evidence is expected to further inform long-term treatment strategies and support broader adoption of RNAi-based therapies for transthyretin amyloidosis.
Vutrisiran is marketed under the brand name AMVUTTRA in multiple regions. In the European Union, the therapy is approved for the treatment of adult patients with hereditary transthyretin amyloidosis with stage 1 or stage 2 polyneuropathy, as well as adults with wild-type or hereditary transthyretin amyloidosis with cardiomyopathy.
Availability of the therapy across European countries remains subject to local reimbursement and market access decisions.
As part of the therapy’s safety information, Alnylam reiterated that treatment with vutrisiran leads to reductions in serum vitamin A levels. Patients receiving therapy are advised to take vitamin A supplementation in amounts approximately ranging from 2,500 IU to 3,000 IU daily, while avoiding excessive supplementation.
Patients who develop ocular symptoms potentially suggestive of vitamin A deficiency, such as night blindness, are advised to consult an ophthalmologist for further evaluation.
Commonly reported adverse reactions associated with vutrisiran treatment include injection site reactions and elevations in blood alkaline phosphatase and alanine transaminase levels.
The continued expansion of evidence supporting vutrisiran reflects broader progress in the treatment landscape for ATTR amyloidosis, a disease that historically had few effective therapeutic options. Advances in RNAi therapeutics and transthyretin-targeting strategies have significantly altered disease management approaches in recent years, offering patients new opportunities for slowing disease progression and improving outcomes.
Alnylam remains one of the leading companies advancing RNAi-based medicines, with a pipeline focused on diseases caused by pathogenic protein expression. The company’s growing clinical evidence base for vutrisiran is expected to further strengthen its position within the rapidly evolving field of genetic medicines and rare cardiovascular disease therapies.
As additional long-term data continue to emerge from HELIOS-B, observational studies, and broader clinical practice, researchers and clinicians will gain further insight into how TTR silencing therapies may shape future standards of care for patients living with ATTR-CM and related transthyretin amyloidosis disorders.
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 isapproved 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 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 genetic 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.
