Therapeutic Benefit of Idebenone in Leber Hereditary Optic Neuropathy: Insights from the LEROS Trial

Cell Rep Med 2024 Mar 19, DOI: 10.1016/j.xcrm.2024.101437

Leber hereditary optic neuropathy (LHON) is a rare mitochondrial disease that causes rapid and severe bilateral vision loss. Idebenone, a synthetic analogue of coenzyme Q10, has previously shown benefits in stabilizing or restoring vision when started within one year of symptom onset. The LEROS study provides important new evidence on its longer-term use.

The LEROS trial (ClinicalTrials.gov NCT02774005) was an open-label, international, multicenter, natural history-controlled study. It evaluated idebenone at 900 mg/day in 199 patients with LHON who were up to five years after symptom onset. Treatment lasted 24 months and results were compared with an external natural history cohort of 372 patients matched by time since symptom onset.

LEROS met its primary endpoint. Idebenone demonstrated clinically relevant benefits at 12 months that continued favorably through 24 months. Benefits were observed in both the subacute/dynamic and chronic phases of the disease. The magnitude of the treatment effect varied according to disease phase, the specific causative mitochondrial DNA (mtDNA) mutation, age, and gender.

The study confirmed a favorable safety profile for idebenone in patients with LHON, consistent with prior clinical experience.

These results support the use of idebenone beyond the first year after symptom onset and help refine clinical management decisions for patients with LHON. The findings highlight the importance of considering disease phase and genetic factors when evaluating expected response.