A review of Eplontersen use in hereditary transthyretin amyloidosis

Hereditary transthyretin amyloidosis is a progressive life-threatening disease characterized by deposition of abnormally folded amyloid fibrils into tissues leading to polyneuropathy and cardiomyopathy. Eplontersen, an antisense oligonucleotide has been FDA approved for the treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States. Eplontersen inhibits the translation of both variant and wildtype transthyretin in the liver, thereby preventing deposition in tissues. In the pivotal Phase III NEURO-TTRansform trial, Eplontersen significantly lowered serum transthyretin concentrations, improving neuropathic impairment and quality of life. Eplontersen was generally well tolerated in the treatment group, with the primary safety effects not significantly different from the control group. Eplontersen is suitable for long term use in patients with disease related polyneuropathy and is currently being studied for use in patients with cardiomyopathy. In this review, we discuss the clinical efficacy, mechanism of action, pharmacology, tolerability, and social determinants of health affecting the use of Eplontersen.