To evaluate the final efficacy and safety analysis of eplontersen at Week 66 in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, open-label NEURO-TTRansform study (NCT04136184). 

ATTRv-PN is a rare, progressive, and debilitating disease caused by accumulation of amyloid fibrils composed of transthyretin (TTR) protein in multiple organ systems. Eplontersen, a ligand-conjugated antisense oligonucleotide that inhibits TTR protein synthesis, is being assessed in the NEURO-TTRansform study. Previously reported topline statistics established that the coprimary endpoints and key secondary endpoint were met at the prespecified Week 35 interim analysis. Eplontersen treatment resulted in significant reductions in serum TTR concentration and neuropathy impairment (modified Neuropathy Impairment Score +7 [mNIS+7]), and improved quality of life (Norfolk Quality of Life-Diabetic Neuropathy score [Norfolk QoL-DN]), compared with external placebo (from the NEURO-TTR study [NCT01737398]). Eplontersen treatment also demonstrated an acceptable safety and tolerability profile.

NEURO-TTRansform enrolled 168 adults with ATTRv-PN, defined by Coutinho Stage 1?2, a documented TTR sequence variant, and signs/symptoms consistent with polyneuropathy (Neuropathy Impairment Score ≥10 and ≤130). Patients were assigned 6:1 to eplontersen 45 mg subcutaneously every 4 weeks (n=144) or inotersen 300 mg once weekly (n=24) until the prespecified Week 35 interim analysis, after which all patients received eplontersen 45 mg subcutaneously every 4 weeks. All patients who received eplontersen were compared with an external placebo group from the NEURO-TTR study at Week 66. Coprimary efficacy assessments at Week 66 included serum TTR concentration, mNIS+7, and the Norfolk QoL-DN score. Safety and tolerability were also assessed.

Full results from the efficacy and safety analysis at Week 66 and Week 35 will be presented.

Results from the final analysis at Week 66 will provide detailed longer-term data on the efficacy and safety of eplontersen in patients with Stage 1 or 2 ATTRv-PN.