Vutrisiran

Hereditary transthyretin amyloid polyneuropathy (ATTR-PN), also called transthyretin familial amyloid polyneuropathy (TTR-FAP), is a rare multisystem disorder due to pathogenic variants of the TTR gene that encodes transthyretin. ATTRv-PN is inherited in an autosomal dominant pattern and primarily presents as damage to peripheral nerves. Liver transplantation, TTR stabilizers, and gene silencing agents are among the therapies for ATTR-PN.
Vutrisiran is a second-generation GalNAc-conjugated siRNA that binds to hepatic TTR mRNA, leading to degradation of its transcripts through the RNA interference (RNAi) mechanism. Vutrisiran has several advantages over first-generation siRNAs (e.g., patisiran): improved stability with a phosphosuccinimidyl backbone, targeted delivery to hepatocytes through GalNAc conjugation, subcutaneous administration with no pre-treatmen, and low dose, long dosing interva. Vutrisiran is a breakthrough in ATTRv-PN treatment that provides a comprehensive list of advantages for ATTRv-PN treatment, including convenient administration, clinically demonstrated efficacy, and a favorable safety profile.

Fig. 1 Mechanism of action of Vutrisiran (b) in treating ATTRv. (Planté-Bordeneuve V.; et al. 2024)