Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients

INTRODUCTION/AIMS: Eplontersen is approved in multiple regions for adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This exploratory analysis was conducted to evaluate the treatment effect of eplontersen by sex in patients with ATTRv-PN from the NEURO-TTRansform trial (NCT04136184). METHODS: Participants in NEURO-TTRansform who received ≥ 1 dose of eplontersen were included in this analysis; participants in the inotersen reference group who switched to eplontersen were excluded. Eplontersen was evaluated in the overall patient population and in a subgroup with cardiomyopathy. Change from baseline in the NEURO-TTRansform primary endpoints of serum transthyretin (TTR) levels to Week 65, modified Neuropathy Impairment Score +7 (mNIS+7) composite score to Week 66, and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) total score to Week 66 were evaluated. A historical placebo group from the NEURO-TTR trial (NCT01737398) was included as a control. RESULTS: The eplontersen group comprised 100 (69.4%) male and 44 (30.6%) female patients. The placebo group comprised 41 (68.3%) male and 19 (31.7%) female patients. For both sexes, treatment with eplontersen decreased serum TTR levels by > 80% (vs. reductions of 3%-13% with placebo), maintained mNIS+7 scores, and improved Norfolk QoL-DN scores (vs. deterioration with placebo). The treatment effect of eplontersen was similar in male and female patients with cardiomyopathy. DISCUSSION: Eplontersen halted neuropathy impairment and improved quality of life versus placebo to a similar degree in both male and female patients with ATTRv-PN, including those with cardiomyopathy. These findings support the use of eplontersen as an effective treatment for ATTRv-PN regardless of sex.