Idebenone in Leber’s Hereditary Optic Neuropathy: A Review of Therapeutic Benefits

Source
Drugs Today, 2016 March, DOI: 10.1358/dot.2016.52.3.2463564

Leber’s hereditary optic neuropathy (LHON) is a rare mitochondrial genetic disorder that causes rapid, progressive, and often permanent bilateral vision loss. Idebenone is currently the only clinically proven treatment option for Leber’s hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, Idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data. Idebenone is a rapidly absorbed, safe and well-tolerated.

Idebenone acts through its antioxidant properties and ability to function as a mitochondrial electron carrier. In patients with LHON, who typically have a deficiency in mitochondrial complex I of the respiratory chain, idebenone bypasses this defect by transferring electrons directly to complex III. This restores cellular energy (ATP) production and reactivates inactive but viable retinal ganglion cells, helping to prevent further vision loss and support vision recovery.

Approval of idebenone for LHON was based on data from a randomized clinical trial, a follow-up study, and real-world evidence. Collectively, these studies demonstrate that oral idebenone at 900 mg/day for 24 weeks provides persistent benefits in preventing additional vision impairment and promoting recovery compared with the natural course of the disease. Benefits have been observed to continue after treatment discontinuation in some cases.

The recommended dosage for adolescents and adults is 900 mg/day (two 150 mg tablets three times daily), taken with food to improve bioavailability. Treatment should be supervised by physicians experienced in managing LHON. Longer-term data beyond 6 months from controlled trials are limited, though real-world experience supports extended use..

Idebenone remains the first and only approved disease-specific treatment for LHON in the European Union and several other countries. No other therapies with comparable neuroprotective or energy-restoring effects have reached the market for this indication. Its favorable safety profile and demonstrated visual benefits make it a cornerstone of current LHON management.