Vutrisiran Beneficial for hATTR Amyloidosis With Polyneuropathy: HELIOS-A Study

Treatment with vutrisiran improved neurologic function and quality of life (QoL) across all severities of hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy, according to study results presented at the 2024 American Academy of Neurology (AAN) annual meeting, held from April 13 to 18, 2024, in Denver, Colorado.

Researchers conducted a post-hoc analysis of a phase 3 trial (HELIOS-A; ClinicalTrials.gov Identifier: NCT03759379) to determine the effect of RNA interference (RNAi) therapeutic vutrisiran on hATTR amyloidosis with polyneuropathy.

Participants were randomly assigned 3:1 to receive 25 mg subcutaneous vutrisiran every 3 months or 0.3 mg/kg intravenous patisiran every 3 weeks (external placebo group from the APOLLO study [ClinicalTrials.gov Identifier: NCT01960348]).

Primary endpoint was change from baseline in modified Neuropathy Impairment Score+7 (mNIS+7) at 9 months.

Participants were categorized into quartiles of increasing NIS scores: quartile 1 (≥5.0-≤20.5; quartile 2 (>20.5-≤44.1); quartile 3 (>44.1-≤73.1); and quartile 4 (>73.1-≤127). Changes from baseline to month 18 were recorded for each quartile for efficacy endpoints.

Vutrisiran was superior to placebo across all quartiles, as observed in mNIS+7 scores at months 9 and 18.

mos=months

Additionally, vutrisiran vs placebo showed improvements across all quartiles for QoL, disability, gait speed, and nutritional status. However, compared with patients with more severe disease (ie, those in the higher quartiles), those with less severe disease (ie, those in the lower quartiles) better maintained NIS scores at month 18. Meanwhile, compared with both groups, the placebo group had worsening scores in all measures at month 18.

Overall, the researchers concluded, “Vutrisiran demonstrated benefit in neurologic function and other key measures, versus external placebo, across all baseline polyneuropathy severities. Patients who initiated vutrisiran earlier in their disease course retained the highest level of neurologic function after 18 months, highlighting the importance of early diagnosis and treatment.”