FDA Approves Eplontersen Injection to Treat Polyneuropathy of Hereditary ATTR

The FDA approved eplontersen injection for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.

Transthyretin amyloidosis is caused by a mutation in the TTR gene, which provides instructions for making the protein transthyretin, according to the National Library of Medicine. The condition is progressive and is characterized by the buildup of abnormal protein deposits called amyloids in the body’s organs and tissues, most frequently in the peripheral nervous system.

The incidence of transthyretin amyloidosis is unknown and varies considerably across various populations for which estimates are available, also according to the NLM.

The efficacy of eplontersen, a transthyretin-directed antisense oligonucleotide, was evaluated in the randomized, open-label, multicenter NEURO-TTRansform trial in adults with polyneuropathy caused by hATTR amyloidosis (NCT04136184). Participants were randomized 6:1 to receive either 45 mg of eplontersen once every four weeks (n=144), or 284 mg of inotersen once per week (n=24) as subcutaneous injections. Ninety-seven percent of eplontersen-treated patients and 83% of inotersen-treated patients completed at least 35 weeks of the assigned treatment.

Efficacy assessments were based on a comparison of the eplontersen arm of this study with an external placebo group (n=60) in another study (NCT01737398) composed of a comparable population of adults with polyneuropathy caused by hATTR amyloidosis.

Treatment with eplontersen resulted in statistically significant improvements at week 35 in both the (objective) modified Neuropathy Impairment Scale+7 (mNIS+7) composite score and the (patient-reported) Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) total score, compared with the external placebo control (P<0.001).

The most common adverse reactions (seen in at least 9% of patients treated with eplontersen) were decreased vitamin A and vomiting.

Full prescribing information is available here.

Eplontersen is marketed by Ionis Pharmaceuticals as Wainua.