Alnylam Presents New Data from the HELIOS-B Phase 3 Study of Vutrisiran in Patients with ATTR Amyloidosis with Cardiomyopathy (ATTR-CM) at the American College of Cardiology’s Annual Scientific Session 2025
Alnylam Pharmaceuticals (ALNY) presented new data from the HELIOS-B Phase 3 study of vutrisiran (AMVUTTRA®) for ATTR amyloidosis with cardiomyopathy at ACC.25. The data follows the recent FDA approval of AMVUTTRA as the first RNAi therapeutic to reduce cardiovascular death, hospitalizations, and urgent heart failure visits in ATTR-CM patients.
Key findings include:
- Improved echocardiographic systolic and diastolic cardiac function compared to placebo
- Maintained or improved functional capacity, health status, and quality of life
- Greatest benefits observed in patients with early-stage disease
- Significant improvements in diastolic function and attenuation of left and right ventricular systolic function declines at Month 18
The study demonstrated vutrisiran's efficacy across various baseline heart failure severities, with results published in JACC. The treatment showed beneficial effects on cardiac structure and function, emphasizing the importance of early intervention in this progressive disease.
Alnylam Pharmaceuticals (ALNY) ha presentato nuovi dati dallo studio di fase 3 HELIOS-B su vutrisiran (AMVUTTRA®) per l'amiloidosi ATTR con cardiomiopatia all'ACC.25. I dati seguono l'approvazione recente da parte della FDA di AMVUTTRA come prima terapia RNAi per ridurre la morte cardiovascolare, i ricoveri ospedalieri e le visite urgenti per insufficienza cardiaca nei pazienti con ATTR-CM.
I risultati chiave includono:
- Funzione cardiaca sistolica e diastolica ecocardiografica migliorata rispetto al placebo
- Capacità funzionale, stato di salute e qualità della vita mantenuti o migliorati
- I maggiori benefici osservati nei pazienti con malattia in fase iniziale
- Miglioramenti significativi nella funzione diastolica e attenuazione dei cali della funzione sistolica ventricolare sinistra e destra al mese 18
Lo studio ha dimostrato l'efficacia di vutrisiran attraverso varie severità di insufficienza cardiaca di base, con risultati pubblicati nel JACC. Il trattamento ha mostrato effetti benefici sulla struttura e sulla funzione cardiaca, sottolineando l'importanza dell'intervento precoce in questa malattia progressiva.
Alnylam Pharmaceuticals (ALNY) presentó nuevos datos del estudio de fase 3 HELIOS-B sobre vutrisiran (AMVUTTRA®) para la amiloidosis ATTR con cardiomiopatía en ACC.25. Los datos siguen a la reciente aprobación de la FDA de AMVUTTRA como la primera terapia de RNAi para reducir la muerte cardiovascular, las hospitalizaciones y las visitas urgentes por insuficiencia cardíaca en pacientes con ATTR-CM.
Los hallazgos clave incluyen:
- Mejora en la función cardíaca sistólica y diastólica ecocardiográfica en comparación con el placebo
- Capacidad funcional, estado de salud y calidad de vida mantenidos o mejorados
- Los mayores beneficios observados en pacientes con enfermedad en etapa temprana
- Mejoras significativas en la función diastólica y atenuación de la disminución de la función sistólica del ventrículo izquierdo y derecho al mes 18
El estudio demostró la eficacia de vutrisiran en diversas severidades de insuficiencia cardíaca basal, con resultados publicados en JACC. El tratamiento mostró efectos beneficiosos sobre la estructura y función cardíaca, enfatizando la importancia de la intervención temprana en esta enfermedad progresiva.
Alnylam Pharmaceuticals (ALNY)는 ACC.25에서 ATTR 심근병증을 위한 vutrisiran (AMVUTTRA®)의 HELIOS-B 3상 연구에서 새로운 데이터를 발표했습니다. 이 데이터는 ATTR-CM 환자에서 심혈관 사망, 입원 및 응급 심부전 방문을 줄이기 위한 첫 번째 RNAi 치료제로서 AMVUTTRA의 최근 FDA 승인을 따릅니다.
주요 발견 사항은 다음과 같습니다:
- 위약에 비해 개선된 심장 기능의 초음파 검사 결과
- 유지되거나 개선된 기능적 능력, 건강 상태 및 삶의 질
- 초기 단계 질환 환자에서 관찰된 가장 큰 이점
- 18개월 시점에서의 이완기 기능의 유의미한 개선 및 좌우 심실 수축 기능 감소의 완화
이 연구는 다양한 기저 심부전의 중증도에서 vutrisiran의 효능을 입증했으며, 결과는 JACC에 발표되었습니다. 이 치료는 심장 구조와 기능에 유익한 효과를 보여주었으며, 이 진행성 질환에서 조기 개입의 중요성을 강조합니다.
Alnylam Pharmaceuticals (ALNY) a présenté de nouvelles données de l'étude de phase 3 HELIOS-B sur vutrisiran (AMVUTTRA®) pour l'amyloïdose ATTR avec cardiomyopathie lors de l'ACC.25. Ces données font suite à l'approbation récente par la FDA d'AMVUTTRA en tant que première thérapie RNAi visant à réduire la mortalité cardiovasculaire, les hospitalisations et les visites urgentes pour insuffisance cardiaque chez les patients atteints d'ATTR-CM.
Les résultats clés incluent:
- Amélioration de la fonction cardiaque systolique et diastolique à l'échocardiographie par rapport au placebo
- Capacité fonctionnelle, état de santé et qualité de vie maintenus ou améliorés
- Les plus grands bénéfices observés chez les patients atteints de maladie à un stade précoce
- Améliorations significatives de la fonction diastolique et atténuation du déclin de la fonction systolique des ventricules gauche et droit au mois 18
L'étude a démontré l'efficacité de vutrisiran à travers différentes gravités d'insuffisance cardiaque de base, avec des résultats publiés dans le JACC. Le traitement a montré des effets bénéfiques sur la structure et la fonction cardiaque, soulignant l'importance d'une intervention précoce dans cette maladie progressive.
Alnylam Pharmaceuticals (ALNY) hat neue Daten aus der HELIOS-B-Phase-3-Studie zu vutrisiran (AMVUTTRA®) für ATTR-Amyloidose mit Kardiomyopathie auf der ACC.25 vorgestellt. Diese Daten folgen auf die kürzliche FDA-Zulassung von AMVUTTRA als erster RNAi-Therapie zur Reduzierung von kardiovaskulären Todesfällen, Krankenhausaufenthalten und dringenden Herzinsuffizienzbesuchen bei ATTR-CM-Patienten.
Wichtige Ergebnisse umfassen:
- Verbesserte echokardiographische systolische und diastolische Herzfunktion im Vergleich zur Kontrollgruppe
- Erhaltene oder verbesserte Funktionsfähigkeit, Gesundheitszustand und Lebensqualität
- Die größten Vorteile wurden bei Patienten mit Frühstadium der Krankheit beobachtet
- Signifikante Verbesserungen der diastolischen Funktion und Minderung des Rückgangs der systolischen Funktion des linken und rechten Ventrikels nach 18 Monaten
Die Studie zeigte die Wirksamkeit von vutrisiran bei verschiedenen Schweregraden der Herzinsuffizienz, wobei die Ergebnisse in JACC veröffentlicht wurden. Die Behandlung zeigte positive Effekte auf die Herzstruktur und -funktion und betonte die Bedeutung einer frühen Intervention bei dieser fortschreitenden Erkrankung.
- FDA approval received for AMVUTTRA as first RNAi therapeutic for ATTR-CM
- Demonstrated efficacy in reducing cardiovascular mortality and hospitalizations
- Significant improvements in cardiac function compared to placebo
- Positive results across multiple clinical endpoints
- Strong efficacy data supporting early-stage treatment
- None.
Insights
Alnylam's new HELIOS-B Phase 3 data significantly strengthens vutrisiran's clinical profile following its recent FDA approval for ATTR-CM. The robust dataset demonstrates meaningful improvements in cardiac function and patient outcomes, establishing vutrisiran as a potential first-line treatment with differentiated administration (just four subcutaneous doses annually).
The data showing benefits across heart failure severities, with greatest efficacy in early-stage disease, is strategically important as it positions vutrisiran for use earlier in the treatment paradigm. This could substantially expand the addressable patient population as diagnostic capabilities improve.
Particularly notable is vutrisiran's impact on both objective cardiac measurements and subjective quality-of-life metrics over 30 months. The publication in JACC adds substantial scientific credibility that will aid physician adoption.
The totality of evidence - including improved cardiac function, reduced mortality, fewer cardiovascular events, and preserved functional capacity - creates a compelling value proposition for payers, patients, and physicians. Alnylam's focus on durability of effect and quality of life addresses critical unmet needs in this progressive, fatal disease, likely strengthening vutrisiran's competitive positioning against tafamidis and other treatment options.
The HELIOS-B data demonstrates vutrisiran's comprehensive benefits in ATTR-CM through three critical mechanisms. First, it directly improves cardiac structure and function, shown by echocardiographic evidence of enhanced diastolic function and attenuated decline in left and right ventricular systolic function compared to placebo.
Second, these improvements translate to meaningful clinical outcomes - with baseline measures of ventricular function providing prognostic information beyond standard biomarker staging systems. The finding that worsening ventricular function correlates with increased mortality risk highlights why vutrisiran's ability to preserve cardiac function is mechanistically important.
Third, vutrisiran delivers patient-centric benefits in functional capacity and quality of life, with greater proportions of treated patients maintaining or improving 6-minute walk distances and Kansas City Cardiomyopathy Questionnaire scores at clinically significant thresholds.
Most remarkable is the superior benefit observed in early-stage disease, reinforcing the need for prompt diagnosis and intervention before significant cardiac remodeling occurs. By addressing TTR production upstream through RNA interference, vutrisiran targets the root cause rather than symptoms, potentially slowing or halting disease progression in a condition previously considered untreatable.
− New Data Follow Recent
− Vutrisiran Favorably Impacted Echocardiographic Systolic and Diastolic Function –
− Vutrisiran Treatment Led to Maintenance or Improvement in Functional Capacity, Health Status, and Quality of Life, Compared to Placebo –
− Benefits of Vutrisiran Observed Across Baseline Heart Failure Severities, with Greatest Benefit in Patients with Early Disease –
− Findings Published in JACC −
“The HELIOS-B study continues to deliver a robust data package showcasing the unique, differentiated value of vutrisiran as a first-line treatment option that can enable patients with ATTR-CM to live longer, better, and healthier lives,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “Data showing beneficial effects on cardiac systolic and diastolic function are novel and indicate the direct impact of vutrisiran in cardiac structure and function of patients living with ATTR-CM. These findings, together with the observed improvements in functional capacity, health status and quality of life, as well as the reductions in all-cause mortality and cardiovascular events, demonstrate the rapid, broad, and sustained impacts of vutrisiran on ATTR-CM and underscore the importance of early intervention for this progressive and ultimately fatal disease.”
Moderated Poster Presentations:
The Relationship Between Cardiac Structure, Function, and Clinical Outcomes and the Impact of Vutrisiran from the HELIOS-B Trial
New echocardiographic data from the HELIOS-B Phase 3 clinical trial, the largest systematic echocardiographic study in a pivotal trial, demonstrated that treatment with vutrisiran improved echocardiographic cardiac function. Vutrisiran treatment led to significant improvements in diastolic function and attenuation of declines in left ventricular (LV) and right ventricular (RV) systolic function at Month 18, compared to placebo. Baseline measures of LV and RV systolic function, as well as indices of diastolic function, were shown to provide important prognostic information beyond clinical characteristics and biomarker-based staging systems. Notably, worsening LV and RV systolic function over 18 months was significantly associated with an increased risk of subsequent all-cause death, highlighting the importance of these parameters in assessing disease progression. The improved clinical outcomes of patients receiving vutrisiran in HELIOS-B may be mediated by its impact on cardiac function.
Impact of Baseline Heart Failure Severity on Efficacy of Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy in the HELIOS-B Trial: A Subgroup Analysis
An exploratory subgroup analysis demonstrated that vutrisiran reduced all-cause mortality and recurrent cardiovascular events across a range of baseline heart failure severities in patients with ATTR-CM. The greatest benefit was observed in patients with earlier, less severe disease, underscoring the need for timely diagnosis and early intervention. Similar effects were seen in the monotherapy population and across additional endpoints, including functional capacity and cardiac biomarkers, reinforcing the efficacy of vutrisiran regardless of disease stage. These results were recently published in JACC.
Maintenance or Improvement of Functional Capacity, Health Status, and Quality of Life with Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy: Data from the HELIOS-B Study
A separate analysis confirmed that vutrisiran significantly maintained or improved functional capacity, and patient-reported health status and quality of life, compared to placebo over 30 months. Greater proportions of patients treated with vutrisiran preserved or improved 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire scores at clinically meaningful thresholds. These findings provide further evidence of vutrisiran’s ability to deliver meaningful benefits beyond reducing mortality and cardiovascular events. These results were recently published in JACC.
An additional Flatboard Poster presentation, “Real-World Persistency on Tafamidis: An Analysis of
To view the results presented at ACC.25, please visit Capella.
About AMVUTTRA® (vutrisiran)
AMVUTTRA® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection by a healthcare professional, 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 and is approved in the
About ATTR
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. 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
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 Pharmaceuticals (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines for 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 ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), 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
Alnylam 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, Alnylam’s expectations regarding the safety and efficacy of vutrisiran for the treatment of ATTR-CM, including the ability of vutrisiran to reduce mortality and cardiovascular events in ATTR-CM patients; the potential of vutrisiran to become a first-line therapy for ATTR-CM; the potential of vutrisiran to enable ATTR-CM patients to live longer, better and healthier lives; and the potential for early treatment with vutrisiran to have beneficial effects in ATTR-CM patients 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” goals; 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; the outcome of litigation; the potential risk of future government investigations; and unexpected expenditures; as well as those risks 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 Alnylam’s views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.
1 Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med. 2015;47(8):625-638.
2 Gertz MA. Am J Manag Care. 2017;23(7):S107-S112.
3 Conceicao I, Gonzalez-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21:5-9.
4 Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.
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Alnylam Pharmaceuticals, Inc.
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Source: Alnylam Pharmaceuticals, Inc.
FAQ
What are the key benefits shown in the HELIOS-B Phase 3 trial for ALNY's vutrisiran?
How does vutrisiran (AMVUTTRA) treat ATTR-CM patients?
What were the echocardiographic results from ALNY's HELIOS-B trial at 18 months?
Which patient group showed the greatest benefit from vutrisiran in the HELIOS-B trial?
What functional improvements were demonstrated in the 30-month HELIOS-B data for ALNY's vutrisiran?
