Researchers based at the University Hospital of the Ludwig-Maximilians-University, Munich, have reported that the idebenone treatment for LHON indicates a better long-term prognosis than expected from limited natural history data. According to researchers from the study, a treatment duration of at least 18–24 months is needed to maximize the probability of clinically relevant recovery (CRR) “because a certain degree of transient deterioration to a nadir may occur despite therapy initiation and continued treatment after an initial CRR provides further benefit”.
LHON is a rare progressive disease with an estimated European prevalence of between 1 in 30,000 and 1 in 50,000 patients. Over 95% of LHON patients carry one of three pathogenic mutations in their mitochondrial DNA causing a defect in the complex I subunit of the mitochondrial respiratory chain, causing progressive loss of visual acuity and blindness. Although small by population size, the indication may represent an attractive market as it represents one of the most common mitochondrial (mtDNA) disorders. Securing market approval in one such mitochondrial disorder may leverage opportunities in other such disorders. Idebenone (marketed by Raxone) is an oral medication originally authorized at a daily dose of 900 mg (given as 2 tablets three times a day with food), for the treatment of visual impairment in adolescent and adult patients. In the current study, idebenone conducted an open-label, multi-center, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrolment.
Eighty-seven (87) patients were provided an average treatment duration of 25.6 months and the results showed that clinically relevant recovery of BCVA was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. According to the report, the average gain in BCVA for responders was 0.72 logMAR, equivalent to more than 7 lines on the ETDRS chart. In addition, the researchers found that 50% of patients with visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. In concluding the clinical study the investigators stated: “these data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy”