Chiesi Global Rare Diseases, a business unit of the Chiesi Group, announced that the US Food and Drug Administration (FDA) is reviewing its regulatory submission for idebenone as a treatment for Leber hereditary optic neuropathy (LHON). The FDA’s target action date is February 28, 2026. If approved, idebenone would become the first clinically proven therapy for LHON in the United States, the company said.
The drug, marketed as Raxone, is already approved in several regions, including the European Union, United Kingdom, Israel, South Korea, Serbia, Switzerland, Chile, Bahrain, and Taiwan.
Chiesi noted that the new drug application accepted by the FDA includes data from randomized, placebo-controlled trials, as well as open-label interventional and observational studies. These studies demonstrated efficacy across the 3 most common mitochondrial DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C) and rarer variants, supporting idebenone’s therapeutic potential in both adult and adolescent patients with LHON.
In the phase 3 RHODOS study, 85 patients with LHON (ages 14–65, disease duration ≤5 years) carrying one of the 3 primary mitochondrial DNA mutations were enrolled in a 24-week, randomized, double-blind, placebo-controlled trial. The primary endpoint was the best recovery of visual acuity (VA), defined as the change from baseline to week 24 in the eye with the most improvement or least deterioration. Patients treated with idebenone (n=53) showed a gain of approximately 6 ETDRS letters, while those receiving placebo (n=28) gained about 1 ETDRS letter (P=.0862).
Statistically significant improvements were also observed in other measures of VA. For overall change in VA, patients in the idebenone group had a mean improvement of –0.037 logMAR (about one ETDRS letter) compared with a worsening of +0.123 logMAR (approximately a 6-letter loss) in the placebo group (P=.0152). Similarly, for change in the best eye, idebenone-treated patients experienced a mean gain of –0.030 logMAR (about one letter), whereas placebo patients worsened by +0.098 logMAR (around 6 letters; P=.0126).
A post hoc responder analysis showed that a greater proportion of idebenone-treated patients achieved clinically meaningful improvements in VA compared with placebo. Findings were consistent across response definitions and supported by propensity score–weighted analyses.
In the phase 4 LEROS study, the primary endpoint was the proportion of eyes achieving a clinically relevant benefit (CRB) at 12 months, defined as either clinically relevant recovery (CRR) or clinically relevant stabilization (CRS) of VA. At 12 months, 42.3% of eyes in the idebenone group achieved CRB compared with 20.7% in the natural history (NH) control group. This benefit was sustained at 24 months, with 52.9% of eyes in the idebenone group achieving CRB versus 36.0% in the NH group (P=.0297). Patients who began treatment more than a year after symptom onset also experienced a significant benefit at 12 months, with 50.3% of eyes in the idebenone group achieving CRB compared with 38.6% in the NH control group (P=.0087).
A post hoc responder analysis further reinforced the clinical relevance of idebenone treatment. The odds of achieving an overall benefit—defined as either achieving CRR or no clinically relevant worsening (meaning visual acuity remained stable without deterioration >0.2 logMAR or transition to off-chart)—were 3.4 times higher in the idebenone group compared with the NH control group.
The most common adverse reactions (incidence ≥3%) included elevated alanine aminotransferase, diarrhea, and elevated aspartate aminotransferase. According to the company, these events were generally mild to moderate, reversible, and rarely led to treatment discontinuation.