HELIOS-A is an ongoing, 18-month, Phase 3 study in patients with ATTRv amyloidosis with polyneuropathy (NCT03759379). Patients were randomized (3:1) to vutrisiran (25 mg subcutaneous injection, every 3 months) or patisiran (0.3 mg/kg intravenous infusion, every 3 weeks), a reference comparator RNAi therapeutic approved for hATTR amyloidosis with polyneuropathy based on the APOLLO study. The APOLLO placebo group (n=77) is an external control. Primary endpoint: change from baseline in neuropathy impairment (modified Neuropathy Impairment Score +7 [mNIS+7]), vs. external placebo at Month 9. Primary analysis population: modified intention-to-treat (randomized patients receiving ≥1 dose of vutrisiran or placebo [mITT]).

HELIOS-A enrolled 164 patients (vutrisiran, n=122; patisiran, n=42), whose characteristics widely overlapped those of the external placebo group. At 9 months, vutrisiran achieved rapid, sustained reduction in serum TTR levels, similar to patisiran. Vutrisiran significantly improved mNIS+7 vs. external placebo (LS mean [±SE] change from baseline: −2.2±1.4 [vutrisiran]; +14.8±2.0 [placebo]; difference, −17.0; p=3.5×10⁻¹²). Vutrisiran also significantly improved quality of life (Norfolk QOL-DN), gait speed (10-meter walk test), nutritional status (modified body mass index), and disability (Rasch-built Overall Disability Scale [R-ODS]) vs. external placebo at Month 9. NT-proBNP levels improved vs. external placebo in the mITT population (adjusted geometric fold change ratio: 0.6; p=9.2×10⁻⁷) and a prespecified cardiac subpopulation. Most adverse events with vutrisiran were mild or moderate. There were no drug-related discontinuations or deaths.

At 9 months, vutrisiran significantly improved multiple disease-relevant endpoints vs. external placebo, with an acceptable safety profile, indicating benefit across numerous important disease manifestations. Efficacy and safety results from the 18-month analysis will be presented at the meeting.