Abstract Details

Title Assessing Clinically Relevant Recovery of Visual Acuity Over Time in Patients with Leber Hereditary Optic Neuropathy Treated with Idebenone: Results from the LEROS Study

Topic Neuro-ophthalmology/Neuro-otology

Presentation(s) S40 - Neuro-ophthalmology/Neuro-otology (1:00 PM-1:12 PM)

Poster/Presentation
Number 001

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.

Objective To assess the long-term efficacy of idebenone in the treatment of Leber hereditary optic neuropathy (LHON).

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.

Authors/Disclosures
Nancy J. Newman, MD, FAAN (Emory University School of Medicine) PRESENTER	Dr. Newman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GenSight. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chiesi. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurophth. The institution of Dr. Newman has received research support from GenSight. The institution of Dr. Newman has received research support from Chiesi/Santhera. The institution of Dr. Newman has received research support from NINDS/NIH. Dr. Newman has received publishing royalties from a publication relating to health care. Dr. Newman has received publishing royalties from a publication relating to health care. Dr. Newman has received publishing royalties from a publication relating to health care.
Patrick Yu-Wai-Man	No disclosure on file
Valerio Carelli, MD, PhD (University of Bologna)	Dr. Carelli has received personal compensation in the range of $0-$499 for serving as a Consultant for Chiesi Farmaceutici. Dr. Carelli has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi Farmaceutici.
Xavier Llòria (Chiesi SpA)	No disclosure on file
Thomas H. Klopstock, MD (University of Munich, Dept. of Neurology)	Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GenSight Biologics. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GenSight Biologics.