Assessing Clinically Relevant Recovery of Visual Acuity Over Time in Patients with Leber Hereditary Optic Neuropathy Treated with Idebenone: Results from the LEROS Study
Nancy Newman1, Patrick Yu-Wai-Man2, Valerio Carelli3, Xavier Llòria4, Thomas Klopstock5
1Emory University School of Medicine, 2John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, University of Cambridge, 3University of Bologna, 4Chiesi SpA, 5University of Munich, Dept. of Neurology
Objective:
To assess the long-term efficacy of idebenone in the treatment of Leber hereditary optic neuropathy (LHON).
Background:
LHON is a mitochondrial disease resulting in bilateral vision loss. In LEROS, a Phase IV, open-label interventional study (ClinicalTrials.gov NCT02774005), visual acuity (VA) outcomes following 24 months of idebenone treatment were compared to an external, matched, Natural History (NH) cohort. LEROS achieved its primary endpoint. Eyes treated with idebenone had significantly higher rates of clinically relevant recovery (CRR) from baseline at 12 and 24 months compared to the NH control group. Here, we present the cumulative percentage of eyes with a CRR (K-M estimate) from nadir and baseline at 24 months as a function of treatment duration by disease phase.
Design/Methods:
LEROS included patients with LHON aged ≥12 years and with a disease onset ≤5 years prior. Patients were stratified by time since symptom onset in the most recent eye: subacute/dynamic (≤1 year) and chronic (>1 year). CRR was defined as an improvement from “off-chart” VA to at least 1.6 logMAR, or a ≥0.2 logMAR improvement if on-chart.
Results:
The intention-to treat (ITT) population included data from 196 patients. In eyes of subacute/dynamic patients, the K-M estimate of a CRR from baseline increased progressively from 18.4% at Month 6, reaching 47.3% at Month 24. In the chronic phase, CRR from baseline increased progressively from 18.2% at Month 6, reaching 29.1% by Month 24. CRR from nadir also increased progressively from 18.5% at Month 6, reaching 57.0% at Month 24 in subacute/dynamic eyes, and from 18.7% at Month 6, reaching 33.7% at Month 24 in chronic eyes. Increases in CRR over time from baseline or nadir were also observed in sub-analyses by mtDNA mutation.
Conclusions:
Regardless of LHON disease stage, the percentage of eyes with improved VA increased progressively over time during idebenone treatment.