Abstract
Purpose :
Leber’s hereditary optic neuropathy (LHON) is a rare mitochondrial disorder resulting in severe, bilateral vision loss. Idebenone is approved in Europe for the treatment of LHON, but controlled data beyond a 6-month treatment duration is lacking. Here, we report results from LEROS, a Phase 4, externally controlled, open-label interventional study (ClinicalTrials.gov NCT02774005), in which visual acuity (VA) outcomes following 24 months of idebenone treatment were compared to an external, matched, natural history (NH) cohort.
Methods :
LEROS included patients with LHON ≥12 years old and with a disease onset ≤5 years prior. Overall, 199 patients were enrolled, 181 of which formed the mITT population (excluded patients without a confirmed primary causative mtDNA mutation). NH data were available from 372 patients. Patients were divided into 2 groups for analysis based on time since onset in the most recent eye: subacute/dynamic (≤1 year) and chronic (>1 year). Outcomes in the idebenone-treated group were compared to retrospective data from the NH cohort, matched based on time since disease 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 <1.0 logMAR; and clinically relevant benefit (CRB): reaching a CRR, a CRS, or both.
Results :
The primary endpoint, the proportion of subacute/dynamic eyes with a CRB from baseline following 12 months of treatment, compared to the matched external NH cohort, was successfully met. CRB was observed in 42.3% (60/142) of treated eyes versus 20.7% (40/193) from the NH cohort (p=0.002). At 24 months, this significant difference was maintained, at 52.9% (64/121) versus 36.0% (27/75) (p=0.0297). In treated subacute/dynamic patients, the median best VA at baseline was 1.28 logMAR (n=109) and showed an initial worsening at 6 months to 1.41 logMAR (n=90). A recovery was then observed to 1.30 (n= 81), 1.20 (n=75) and 1.07 (n=70) logMAR at 12, 18 and 24 months, respectively. No new safety signals were observed for idebenone.
Conclusions :
LEROS corroborates the outcomes of previous studies, demonstrating that long-term treatment with idebenone results in prolonged clinical benefit in patients with LHON in the subacute/dynamic phase.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.