EPLONTERSEN: A NEW HOPE FOR CARDIAC COMPLICATIONS IN ATTR POLYNEUROPATHY

Transthyretin is essential for transporting retinol and thyroxine, produced mainly in the liver. TTR amyloidosis occurs when misfolded TTR aggregates form amyloid fibrils, leading to organ dysfunction. FAP (Familial amyloid polyneuropathy linked to mutations like the V30M variant, causes progressive sensory and autonomic neuropathy with a poor prognosis if untreated. TTR-related cardiomyopathy involves amyloid deposition in the heart, resulting in heart failure. The NEURO-TTRansform trial methodology provides a robust framework for evaluating the efficacy and safety of Eplontersen in patients with ATTRv-PN and ATTR-CM. The detailed assessment of both clinical outcomes and pharmacokinetics contributes to understanding Eplontersen’s potential as a transformative therapy for this patient population. Recent treatment advancements include eplontersen that reduces TTR production by targeting TTR mRNA, effectively preventing amyloid fibril formation. Clinical trials, such as the NEURO-TTRansform study, demonstrated significant efficacy: eplontersen led to an adjusted mean reduction in serum TTR levels of -81.7% compared to placebo, along with improvements in neuropathy impairment (mNIS+7 score change of -24.8, P < 0.001) and quality of life (Norfolk QoL-DN score change of -19.7, P < 0.001). Eplontersen also showed a 4.3% improvement in left ventricular ejection fraction among hATTR-CM patients. Adverse events were manageable, with two deaths linked to disease complications. Ongoing research is focused on eplontersen’s long-term effects and its potential in treating ATTR-CM. These findings highlight eplontersen’s promise as a transformative therapy for hATTR, improving both neuropathy and cardiac outcomes while enhancing patient quality of life.