The HELIOS-B Trial

Summary for Physicians: Vutrisiran Approval and Key Trial Results in ATTR-CM

Vutrisiran approval based on HELIOS-B trial: Vutrisiran, a transthyretin silencer, was recently approved for the treatment of patients with transthyretin amyloid cardiomyopathy (ATTR-CM), based on the positive results from the HELIOS-B trial. Dr Soman discusses the top-line results and their clinical implications:

• Design: The HELIOS-B trial was a phase 3, randomized, placebo-controlled study that assessed the efficacy and safety of vutrisiran in patients with ATTR-CM. It specifically focused on reducing TTR levels and improving clinical outcomes such as cardiac function, quality of life, and hospitalizations.
• End points: The primary end point was a composite measure of all-cause mortality and cardiovascular-related hospitalizations, whereas secondary end points included biomarkers of cardiac function, physical functioning (eg, 6-minute walk test), and quality of life.
• Efficacy: Vutrisiran demonstrated significant efficacy in reducing TTR levels and improving key clinical outcomes. Patients treated with vutrisiran showed a lower rate of cardiovascular-related hospitalizations and improved functional capacity compared with the placebo group.
• Safety: The drug was generally well tolerated, with adverse events similar to those seen in other silencer therapies. There were no new safety signals, supporting its use in this patient population.

Clinical implications: The approval of vutrisiran represents a major advancement in the treatment of ATTR-CM, providing an additional therapeutic option for patients. Given its effectiveness in reducing TTR levels and improving patient outcomes, vutrisiran is expected to become an important treatment choice, especially for those unable to tolerate other therapies.

Summary of results from the 3 trials: Dr Soman also summarized the key findings from 3 pivotal trials:

1. HELIOS-B (vutrisiran): Demonstrated significant efficacy in reducing TTR levels and improving cardiovascular outcomes in patients with ATTR-CM, leading to its approval.
2. ATTR-ACT (tafamidis): Showed that tafamidis improves survival and reduces hospitalizations in patients with ATTR-CM, solidifying its role as a first-line treatment.
3. ATTRibute-CM (acoramidis): Found that acoramidis improves cardiac function and outcomes in ATTR-CM, with a favorable safety profile.

Together, these trials reinforce the growing therapeutic arsenal available for managing ATTR-CM, offering clinicians a range of options to personalize treatment and optimize patient outcomes.