Vutrisiran (ALN-TTRsc02) is an investigational, liver-directed small interfering ribonucleic acid (siRNA) compound designed for research on transthyretin (TTR)-mediated amyloidosis.

Vutrisiran (formerly ALN-TTRSC02) is being developed as a second-generation RNAi therapeutic for treating ATTR amyloidosis. It features an siRNA designed to target a common sequence in the TTR mRNA, relevant to both wild-type and all known TTR variants. Incorporating enhanced stabilization chemistry (ESC), and attached to a triantennary GalNAc ligand, Vutrisiran aims to facilitate less frequent, subcutaneous (SC) administration[1].

In non-human primates, single subcutaneous (SC) doses of Vutrisiran at 0.3 and 1 mg/kg resulted in mean maximum transthyretin (TTR) reductions (nadirs) of 55% and 96% respectively, with the latter dose maintaining serum TTR reductions for over four months. Monthly administrations of 1 and 3 mg/kg consistently upheld TTR level reductions at 96% compared to baseline[1].