Why carry out this study?

Hereditary transthyretin amyloidosis (hATTR) is a fatal disease caused by mutations in the transthyretin (TTR) gene that result in the synthesis of unstable TTR tetramers and consequent systemic deposition of insoluble amyloid fibrils, which most often manifest as cardiomyopathy or polyneuropathy (hATTR-PN).

Although existing treatments can slow or halt neurologic impairment associated with hATTR-PN, there remains a need for other disease-modifying agents that offer improved efficacy, safety, and convenience of use.

AKCEA-TTR-LRx is a novel antisense oligonucleotide (ASO) designed for enhanced delivery to hepatocytes, the primary site of TTR protein production, for increased potency and convenience of use to potentially translate into clinical and quality-of-life benefits for patients with hATTR-PN.

This paper describes the design and rationale of the NEURO-TTRansform trial, a multicenter, open-label, randomized, phase 3 study that aims to assess the efficacy and safety of AKCEA-TTR-LRx in approximately 140 adult patients with stage 1 (independent ambulation) or 2 (requiring ambulatory support) hATTR-PN.