Written by Peter Liu
Spoon Feed
Vutrisiran demonstrated a significant mortality benefit and improved preservation of functional capacity and quality of life in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) in the HELIOS-B Trial.
Vutrisiran adds to tafamidis for disease-specific treatment of ATTR amyloidosis
ATTR-CM is a common cause of heart failure with high morbidity and mortality. It likely accounts for over 10% of preserved EF heart failure (HFpEF) in patients over 60, and 4-year mortality rates for ATTR cardiomyopathy range from 18-57%. To date, tafamidis, a TTR stabilizer, has been the only disease-specific medication that improved mortality. Now, there appears to be a second medication: vutrisiran, a subcutaneous RNA interference therapeutic administered once every 3 months that inhibits TTR synthesis. In the HELIOS-B RCT of 655 patients, performed in the United Kingdom, vutrisiran significantly reduced all-cause mortality and recurrent cardiovascular events (HR 0.72, 95%CI 0.56–0.93, p=0.01), reduced all-cause mortality alone (HR 0.69, 0.49-0.98, p=0.04) and resulted in better 6-minute walk test and Kansas City Cardiomyopathy Questionnaire results on follow-up. Of these patients, 40% were also on tafamidis. Patient benefits from vutrisiran seemed to be similar both in the vutrisiran monotherapy subgroup and in the total study population.
How does this change my practice?
The combination of positive findings from HELIOS-B as well as HELIOS-A (vutrisiran for patients with neuropathy from hereditary transthyretin amyloidosis) puts vutrisiran on the map as a disease-specific therapy for patients with ATTR amyloidosis. So far, however, patient benefit has only been reported in one country in an industry-funded study. I look forward to more evidence of patient benefit in other patient populations and non-study settings in the future.
Source
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: 39213194
