Vutrisiran-mediated knockdown of TTR in patients with transthyretin amyloidosis

ESC Heart Failure 2026 – In HELIOS-A and HELIOS-B, treatment with vutrisiran led to rapid and sustained reductions in serum TTR levels in patients with ATTRv-PN and ATTR-CM.

This summary is based on the presentation of Vincent Algalarrondo, MD, PhD (Paris, France) at the ESC Heart Failure Congress 2026 - Vutrisiran-mediated knockdown of transthyretin in patients with transthyretin amyloidosis.

Introduction and methods

Transthyretin amyloidosis (ATTR) is a progressive, fatal disease caused by misfolded TTR protein accumulating as amyloid fibrils in multiple organs, including in the peripheral nervous system and in the heart. Vutrisiran is an RNAi therapeutic that inhibits the hepatic production of TTR, resulting in rapid knockdown of amyloidogenic TTR protein. The effects of vutrisiran in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN) and transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) were evaluated in the HELIOS-A and HELIOS-B trials, respectively.

The aim of this analysis was to assess the consistency of serum TTR knockdown with vutrisiran across patients with ATTRv-PN in HELIOS-A and ATTR-CM in HELIOS-B.

HELIOS-A was a randomized, open-label, phase 3 study in which 164 patients with ATTRv-PN were randomized in a 3:1 ratio to vutrisiran 25 mg SC Q3M or patisiran 0.3 mg/kg IV Q3W for 18 months. Data were compared to the placebo group (n=77) from the APOLLO trial.

HELIOS-B was a randomized, placebo-controlled, double-blind, phase 3 study in which 654 patients with ATTR-CM were randomized in a 1:1 ratio to vutrisiran 25 mg SC Q3M or placebo up to 36 months.

Main results

• There was a rapid and sustained reduction in serum TTR with vutrisiran in both the HELIOS-A and HELIOS-B trials.
• In HELIOS-A, the median reduction in TTR with vutrisiran was 91% at month 18.
• In HELIOS-B, the median reduction in TTR with vutrisiran was 87% at month 30.
• In HELIOS-B, the effects on serum TTR knockdown at month 30 were generally consistent across subgroups, including baseline characteristics, tafamidis use, and measures of baseline disease severity.
• In HELIOS-A, the effects on serum TTR knockdown at month 18 were also generally consistent across subgroups.

Conclusion

Treatment with vutrisiran led to rapid and sustained TTR knockdown across HELIOS-A and HELIOS-B in patients with ATTRv-PN and ATTR-CM.

- Our reporting is based on the information provided at the ESC Heart Failure Congress 2026 -