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Vutrisiran offers a new lifeline to patients with progressive heart condition

Cardiovascular Pharmacotherapy


Key take-aways 

  • Transthyretin amyloidosis (ATTR) is a progressive disease in which amyloid deposits accumulate in organs, such as the heart, causing cardiomyopathy.  
  • In the HELIOS-B trial, vutrisiran significantly reduced mortality and cardiovascular events compared with placebo in patients with ATTR with cardiomyopathy. 
  • Vutrisiran significantly reduced markers of disease progression compared with placebo, with an acceptable safety profile.  

 

London, United Kingdom – 30 August 2024: Vutrisiran significantly improved mortality, cardiovascular events and markers of disease progression in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), according to late-breaking research presented in a Hot Line session today at ESC Congress 2024.1 

“ATTR is a progressive, fatal disease in which misfolded transthyretin protein accumulates as amyloid deposits in various parts of the body, often damaging the heart. We investigated whether a novel RNA interference (RNAi) therapeutic, vutrisiran, which targets transthyretin production, could improve clinical outcomes in patients with ATTR-CM and the results were very promising,” explained Principal Investigator, Professor Marianna Fontana from University College London, Royal Free Hospital, London, UK. 

HELIOS-B was a randomised, double-blind trial in patients with ATTR-CM (hereditary or wild-type) who had evidence of cardiac amyloidosis by echocardiography and confirmed ATTR amyloid deposition. Patients were randomised in a 1:1 ratio to vutrisiran 25 mg or placebo administered subcutaneously once every 3 months for up to 36 months. If the patient was already receiving treatment with the disease stabiliser, tafamidis, this was continued.  

The two primary endpoints were a composite of all-cause mortality and recurrent cardiovascular events when the last patient reached month 33, assessed in the overall population and in patients taking vutrisiran monotherapy (i.e. those not taking tafamidis at baseline). Secondary endpoints (assessed in the overall population and in those on vutrisiran monotherapy) were all-cause mortality up to 42 months, change from baseline to 30 months in functional capacity (6-minute walk test), quality of life (Kansas City Cardiomyopathy Questionnaire Overall Summary) and New York Heart Association (NYHA) class. 

In total, 655 patients were recruited from 87 centres in 26 countries. The median age was 76.5 years and 92.5% were male. More than three-quarters (77.6%) had heart failure of NYHA class 2 and 40% were taking tafamidis at baseline. 

The trial met the primary endpoints. Vutrisiran significantly reduced the risk of all-cause mortality and recurrent cardiovascular events by 28% in the overall population (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.56–0.93; p=0.01) and by 33% in the monotherapy population (HR 0.67; 95% CI 0.49–0.93; p=0.016). In a prespecified subgroup analysis, the composite of all-cause mortality and recurrent cardiovascular events was reduced by more than 20% in patients on background tafamidis (HR 0.79; 95% CI 0.51–1.21). 

Vutrisiran reduced all-cause mortality over 42 months by 36% in the overall population (HR 0.64; 95% CI 0.46–0.90; p=0.01) and by 35% in the monotherapy population (HR 0.65; 95% CI 0.44–0.97; p=0.045) vs. placebo. Other secondary endpoints related to functional capacity, health status and quality of life were significantly improved with vutrisiran vs. placebo. 

The majority of adverse events were mild or moderate with vutrisiran. Adverse events leading to study drug discontinuation were similar in the vutrisiran (3.1%) and placebo (4.0%) groups. 

Professor Fontana concluded: “Vutrisiran was highly effective and well tolerated in this contemporary population representative of patients that we see in our clinics, with consistent benefits regardless of background tafamidis therapy. Our findings indicate that vutrisiran has the potential to become the new standard of care. This trial is also important as it is the first to show the benefit of gene silencers in any type of cardiomyopathy.”  

ENDS 

Notes to editor

This press release accompanies both a presentation and an ESC press conference at ESC Congress 2024. It does not necessarily reflect the opinion of the European Society of Cardiology. 

 

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Funding: The study was funded by Alnylam.  

Disclosures: Marianna Fontana reports being on consultancy/advisory boards for Alnylam, Alexion/Caelum Biosciences, AstraZeneca, Bridgbio/Eidos, Prothena, Attralus, Intellia Therapeutics, Ionis Pharmaceuticals, Cardior, Lexeo Therapeutics, Janssen Pharmaceuticals, Prothena, Pfizer and Novo Nordisk. Research grants from: Alnylam, Bridgbio, AstraZeneca and Pfizer. Salary from British Heart Foundation Intermediate Fellowship. Share options in LexeoTherapeutics and shares in Mycardium 

 

References and notes 

1‘HELIOS-B - Primary results from phase 3 study of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy’ will be discussed during Hot Line 1 on Friday 30 August in room London. 

 

About ESC Congress 2024 

It is the world’s largest gathering of cardiovascular professionals, disseminating ground-breaking science both onsite in London and online – from 30 August to 2 September. Explore the scientific programme. More information is available from the ESC Press Office at press@escardio.org. 

About the European Society of Cardiology

The ESC brings together health care professionals from more than 150 countries, working to advance cardiovascular medicine and help people to live longer, healthier lives.