Comparison of efficacy outcomes with Vutrisiran vs. Patisiran in hATTR amyloidosis with polyneuropathy: post-hoc analysis of the HELIOS-A study

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Introduction: Vutrisiran and patisiran are approved RNAi therapeutics that reduce TTR protein production to treat hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy (PN). Objectives: Assess the relative efficacy of RNAi therapeutics for hATTR amyloidosis with PN. Methods: In the Phase 3 HELIOS-A study (NCT03759379), patients with hATTR amyloidosis with PN were randomized to vutrisiran (25 mg SC, Q3M) or patisiran (0.3 mg/kg IV, Q3W). Comparison of TTR reduction between vutrisiran and patisiran was included as a secondary endpoint. Here, post-hoc analyses comparing vutrisiran and patisiran arms on clinical outcomes are reported: neuropathy (mNIS+7), quality of life (Norfolk-QOL-DN), gait speed (10-MWT), nutritional status (mBMI), and disability (R-ODS). Results: TTR reduction with vutrisiran was non-inferior to that observed with patisiran (median difference [95% confidence interval], 5.28% [1.17, 9.25]). Leastsquares mean (±SE) changes from baseline to Month 18 for vutrisiran and patisiran, respectively, showed similar effects: mNIS+7 (0.06 ± 1.48 versus 1.53 ± 2.59; P = 0.6248), Norfolk-QOL-DN (−2.5 ± 1.8 versus −0.8 ± 3.0; P = 0.6472), 10-MWT (-0.019 ± 0.025 versus −0.053 ± 0.043 m/s; P = 0.4936), mBMI (21.8 ± 9.2 versus 7.6 ± 15.8; P = 0.4378), and R-ODS (−1.2 ± 0.5 versus −1.3 ± 0.9; P = 0.9266). Conclusion: Vutrisiran and patisiran showed numerically and statistically similar efficacy for treating the polyneuropathy manifestations of hATTR amyloidosis and have similar pharmacodynamic effects in terms of TTR lowering.