Long‐term efficacy and safety of idebenone in patients with Leber's hereditary optic neuropathy (LHON) in the subacute/dynamic phase: Results from the prospective, natural history‐controlled LEROS study

Purpose: Idebenone is approved in Europe for the treatment of LHON – a rare mitochondrial disorder resulting in severe, bilateral vision loss. Controlled data beyond a 6‐month treatment duration is lacking. Here, we report primary results from LEROS, a Phase 4, externally controlled interventional study in patients with subacute/dynamic LHON treated with idebenone for up to 24 months. Methods: Patients with LHON onset ≤5 years prior were enrolled and stratified by time since onset: subacute/dynamic (≤1 year) and chronic (>1 year). Visual acuity (VA) outcomes from 181 patients, treated for up to 24 months were compared to retrospective data from an external natural history (NH) cohort (N = 372) matched by time since onset. Outcome measures, from baseline, were clinically relevant recovery (CRR): improvement from ‘off‐chart’ VA to at least 1.6 logMAR, or a ≥0.2 logMAR improvement if already ‘on‐chart’; clinically relevant stabilization (CRS): maintenance of VA