HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
HELIOS-B: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
2 other identifiers
interventional
655
31 countries
116
Brief Summary
This study will evaluate the efficacy and safety of vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) compared to placebo in participants with ATTR amyloidosis with cardiomyopathy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2019
Longer than P75 for phase_3
116 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 4, 2019
CompletedFirst Posted
Study publicly available on registry
November 6, 2019
CompletedStudy Start
First participant enrolled
November 26, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 8, 2024
CompletedResults Posted
Study results publicly available
October 21, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 2, 2026
ExpectedJanuary 12, 2026
December 1, 2025
4.5 years
November 4, 2019
June 18, 2025
December 18, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.
Up to Month 36
Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.
Up to Month 36
Secondary Outcomes (7)
Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population
Baseline to Month 30
Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup
Baseline to Month 30
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population
Baseline to Month 30
Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup
Baseline to Month 30
All-cause Mortality in the Overall Population and Vutrisiran Monotherapy Subgroup
Up to 42 months
- +2 more secondary outcomes
Study Arms (2)
Vutrisiran 25 mg
EXPERIMENTALParticipants received vutrisiran 25 milligrams (mg) administered subcutaneously (SC) once every 3 months (q3M) during the 36-month double-blind (DB) period. After the DB period, participants continue receiving vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the open-label treatment extension (OLE) period.
Placebo
PLACEBO COMPARATORParticipants received vutrisiran matching placebo administered SC q3M during the 36-month DB period. After the DB period, participants receive vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the OLE period.
Interventions
Vutrisiran will be administered by SC injection.
Sterile normal saline (0.9% NaCl) will be administered by SC injection.
Eligibility Criteria
You may qualify if:
- Has a documented diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as either hereditary ATTR (hATTR) amyloidosis with cardiomyopathy or wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy meeting pre-specified diagnostic criteria
- Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF OR clinical evidence of HF
You may not qualify if:
- Has known primary amyloidosis or leptomeningeal amyloidosis
- Has New York Heart Association (NYHA) Class IV heart failure
- Has NYHA Class III heart failure AND is at high risk based on pre-specified criteria
- Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV at the Screening visit
- Has estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m\^2
- Has received prior TTR-lowering treatment
- Has other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (119)
Clinical Trial Site
La Mesa, California, 91942, United States
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Los Angeles, California, 90033, United States
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Stanford, California, 94305, United States
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Washington D.C., District of Columbia, 20010, United States
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Gainesville, Georgia, 30501, United States
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Chicago, Illinois, 60637, United States
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Evanston, Illinois, 60201, United States
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Boston, Massachusetts, 02115, United States
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Boston, Massachusetts, 02118, United States
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Rochester, Minnesota, 55902, United States
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Manhasset, New York, 11030, United States
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New York, New York, 10032, United States
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Durham, North Carolina, 27710, United States
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Cleveland, Ohio, 44195, United States
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Allentown, Pennsylvania, 18103, United States
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Philadelphia, Pennsylvania, 19104, United States
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Houston, Texas, 77030, United States
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Buenos Aires, Ciudad Autónoma de BuenosAires, C1093AAS, Argentina
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Buenos Aires, Pilar, B1629ODT, Argentina
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Buenos Aires, C1199ABB, Argentina
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Buenos Aires, C1428ART, Argentina
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Darlinghurst, New South Wales, 2010, Australia
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Northmead, New South Wales, 2152, Australia
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Woolloongabba, Queensland, 4102, Australia
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Adelaide, South Australia, 5000, Australia
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Melbourne, Victoria, 3004, Australia
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Graz, 8036, Austria
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Vienna, 1090, Austria
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Vienna, 1210, Austria
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Dendermonde, Oost-Vlaanderen, 9200, Belgium
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Ghent, Oost-Vlaanderen, 9000, Belgium
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Brussels, 1070, Belgium
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Leuven, 3000, Belgium
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Toronto, Ontario, M5G 2C4, Canada
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Québec, Quebec, G1V4G5, Canada
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Zagreb, 10000, Croatia
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Olomouc, Olomoucký kraj, 779 00, Czechia
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Prague, Praha, Hlavní Mesto, 12000, Czechia
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Odense, Region Syddanmark, 5000, Denmark
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Aarhus N, 8200, Denmark
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Créteil, 94000, France
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Marseille, 13385, France
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Paris, 75877, France
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Toulouse, 31059, France
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Frankfurt am Main, Hesse, 60313, Germany
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Leipzig, Saxony, 04103, Germany
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Essen, 45122, Germany
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Göttingen, 37075, Germany
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Heidelberg, 69120, Germany
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Münster, 48149, Germany
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Würzburg, 97078, Germany
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Budapest, 1088, Hungary
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Budapest, 1134, Hungary
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Szeged, 6725, Hungary
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Dublin, D07 A8NN, Ireland
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Dublin, Dublin 8, Ireland
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Haifa, 3339419, Israel
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Jerusalem, 9112000, Israel
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Ramat Gan, 5262000, Israel
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Tsurumai-cho, Aichi-ken, 466-8560, Japan
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Fukuoka, Fukuoka, 810-0001, Japan
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Kurume, Fukuoka, 830-0011, Japan
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Kita-gun, Kagawa-ken, 761-0793, Japan
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Nankoku, Kochi, 783-8505, Japan
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Matsumoto, Nagano, 390-8621, Japan
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Kashihara, Nara, 634-8522, Japan
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Suita, Osaka, 564-8565, Japan
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Suita, Osaka, 565-0871, Japan
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Bunkyo-ku, Tokyo, 113-8431, Japan
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Bunkyo-ku, Tokyo, 113-8655, Japan
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Shinjuku-Ku, Tokyo, 160-8582, Japan
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Fukuoka, 812-8582, Japan
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Kumamoto, 860-8556, Japan
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Riga, LV-1002, Latvia
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Hamra, Beyrouth, 1111, Lebanon
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Kaunas, LT-50161, Lithuania
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Kuantan, Pahang, 25100, Malaysia
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Sungai Buloh, Selangor, 47000, Malaysia
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Chisinau, MD2025, Moldova
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Eindhoven, 5623 EJ, Netherlands
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Groningen, 9713 GZ, Netherlands
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Utrecht, 3584 CW, Netherlands
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Oslo, 0424, Norway
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San Isidro, Lima region, 15076, Peru
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Lima, 15088, Peru
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Wroclaw, Lower Silesian Voivodeship, 50-556, Poland
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Lodz, Lódzkie, 90-127, Poland
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Warsaw, Masovian Voivodeship, 01-192, Poland
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Gdansk, Pomeranian Voivodeship, 80-382, Poland
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Katowice, 40-555, Poland
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Lisbon, Lisbon District, 1649-035, Portugal
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Coimbra, 3000-075, Portugal
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Faro, 8000-386, Portugal
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Guimarães, 4835-044, Portugal
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Porto, 4099-001, Portugal
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Mecca, Mecca Region, 21955, Saudi Arabia
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Riyadh, 12372, Saudi Arabia
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Ljubljana, 1000, Slovenia
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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L'Hospitalet de Llobregat, Barcelona, 08907, Spain
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Majadahonda, Madrid, 28222, Spain
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Barcelona, 08035, Spain
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Bilbao, 48013, Spain
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Huelva, 21005, Spain
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Málaga, 29010, Spain
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Göteborg, Västerbotten County, 422 46, Sweden
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Gothenburg, 422 46, Sweden
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Chiang Mai, 50200, Thailand
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Bellshill, Lanarkshire, ML4 3NJ, United Kingdom
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London, London, City of, SE1 1YR, United Kingdom
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Londonderry, Londonderry, BT47 6SB, United Kingdom
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Hexham, Northumberland, NE46 1QJ, United Kingdom
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Birmingham, B15 2SQ, United Kingdom
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Cardiff, CF15 9SS, United Kingdom
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London, NW3 2QG, United Kingdom
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Manchester, M15 6SE, United Kingdom
Related Publications (7)
Claggett BL, Fontana M, Vaduganathan M, Hamatani Y, Maurer MS, Gillmore JD, Solomon SD. Timing of Mortality Benefit in Outcomes Trials in Transthyretin Amyloidosis. J Am Coll Cardiol. 2026 Feb 10;87(5):522-529. doi: 10.1016/j.jacc.2025.09.1512. Epub 2025 Sep 25.
PMID: 41225306DERIVEDJering KS, Fontana M, Lairez O, Longhi S, Azevedo O, Morbach C, Bender S, Jay PY, Vest J, Bulwer BE, Prasad N, Solomon SD, Skali H. Effects of vutrisiran on cardiac structure and function in patients with transthyretin amyloidosis with cardiomyopathy: secondary outcomes of the HELIOS-B trial. Nat Med. 2025 Oct;31(10):3560-3568. doi: 10.1038/s41591-025-03851-z. Epub 2025 Aug 6.
PMID: 40770082DERIVEDMaurer MS, Berk JL, Damy T, Sheikh FH, Gonzalez-Costello J, Morbach C, Delgado D, Bondue A, Azevedo O, Poulsen SH, Jankowska EA, Yang L, Bender S, Eraly SA, Jay PY, Vest J, Fontana M. Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B. J Am Coll Cardiol. 2025 Aug 12;86(6):459-475. doi: 10.1016/j.jacc.2025.04.055.
PMID: 40769675DERIVEDWitteles RM, Garcia-Pavia P, Damy T, Grogan M, Sheikh FH, Morbach C, Bender S, Exter J, Eraly SA, Fontana M. Vutrisiran Improves Survival and Reduces Cardiovascular Events in ATTR Amyloid Cardiomyopathy: HELIOS-B. J Am Coll Cardiol. 2025 Apr 30:S0735-1097(25)06170-4. doi: 10.1016/j.jacc.2025.04.008. Online ahead of print.
PMID: 40380962DERIVEDMaurer MS, Witteles RM, Garcia-Pavia P, Sheikh FH, Morbach C, Rodriguez Duque D, Aldinc E, Eraly SA, Gillmore JD. Impact of Heart Failure Severity on Vutrisiran Efficacy in Transthyretin Amyloidosis With Cardiomyopathy. J Am Coll Cardiol. 2025 May 27;85(20):1927-1939. doi: 10.1016/j.jacc.2025.03.477. Epub 2025 Mar 17.
PMID: 40099776DERIVEDFontana M, Maurer MS, Gillmore JD, Bender S, Aldinc E, Eraly SA, Jay PY, Solomon SD. Outpatient Worsening Heart Failure in Patients With Transthyretin Amyloidosis With Cardiomyopathy in the HELIOS-B Trial. J Am Coll Cardiol. 2025 Feb 25;85(7):753-761. doi: 10.1016/j.jacc.2024.11.015. Epub 2024 Nov 18.
PMID: 39566871DERIVEDFontana M, Berk JL, Gillmore JD, Witteles RM, Grogan M, Drachman B, Damy T, Garcia-Pavia P, Taubel J, Solomon SD, Sheikh FH, Tahara N, Gonzalez-Costello J, Tsujita K, Morbach C, Pozsonyi Z, Petrie MC, Delgado D, Van der Meer P, Jabbour A, Bondue A, Kim D, Azevedo O, Hvitfeldt Poulsen S, Yilmaz A, Jankowska EA, Algalarrondo V, Slugg A, Garg PP, Boyle KL, Yureneva E, Silliman N, Yang L, Chen J, Eraly SA, Vest J, Maurer MS; HELIOS-B Trial Investigators. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. N Engl J Med. 2025 Jan 2;392(1):33-44. doi: 10.1056/NEJMoa2409134. Epub 2024 Aug 30.
PMID: 39213194DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Alnylam Pharmaceuticals Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Alnylam Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 4, 2019
First Posted
November 6, 2019
Study Start
November 26, 2019
Primary Completion
May 8, 2024
Study Completion (Estimated)
December 2, 2026
Last Updated
January 12, 2026
Results First Posted
October 21, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more. Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.