Eplontersen

Masri A, et al. Journal of Cardiac Failure, 2024, 30(8), 973-980.

Eplontersen is designed to inhibit transthyretin (TTR) protein production, addressing hereditary transthyretin amyloidosis (ATTRv). The therapeutic potential of eplontersen in stabilizing and improving cardiac function in ATTRv patients was evaluated in the NEURO-TTRansform trial.
This open-label study included 144 patients with ATTRv polyneuropathy, 34% of whom exhibited cardiomyopathy. Outcomes from 65 weeks of eplontersen treatment were compared with a historical placebo group (n=60) from the NEURO-TTR trial. Significant cardiac improvements were observed in the cardiomyopathy subgroup, notably an increase in left ventricular ejection fraction (LVEF) by 4.3% and stroke volume by 10.64 mL relative to placebo. These findings reflect enhanced cardiac output and efficiency, critical for mitigating cardiomyopathy-associated morbidity. Importantly, other echocardiographic parameters remained stable, highlighting the drug's role in halting disease progression.
Eplontersen's mechanism involves silencing the TTR gene, thereby reducing circulating amyloidogenic protein levels and alleviating amyloid deposition in the myocardium. This targeted approach addresses both the root cause and systemic manifestations of ATTRv.
The results of NEURO-TTRansform affirm eplontersen's efficacy in improving cardiac metrics and maintaining structural integrity in ATTRv-related cardiomyopathy.