Santhera Pharmaceuticals announced positive topline results from itslong-term Phase 4 LEROS study with Raxone® (idebenone) in the treatment of Leber’s hereditary optic neuropathy (LHON). The primary endpoint, proportion of eyes with clinically relevant benefit after 12 months treatment with Raxone versus untreated patients from an external control group, was met with high statistical significance (p=0.002). The efficacy data confirm and extend previous findings which demonstrated that Raxone can prevent further vision loss and promote recovery of visionin LHONpatients. Santhera holds the EU marketing authorization for Raxone (idebenone) and out-licensed rights to the product outside North America and France for the treatment of LHON to Chiesi Group. Subject to the achievement of certain commercial milestones for Raxone, Santhera is entitled to contingent variable near- to mid-term milestone payments from Chiesi Group of up to EUR 49 million. LEROS, a Phase 4 externally-controlled open-label intervention study, was designed to confirm the efficacy of Raxone in patients with LHON after 12 months of treatment and to further assess the long-term efficacy and safety of Raxone over 24 months (ClinicalTrials.gov Identifier: NCT02774005). The study, which was designed with guidance and approval from the European Medicines Agency (EMA), together with the natural history data collection used as an external control, were part of a post-authorization commitment. The positive results confirm and extend earlier findings from the double-blind, randomized, placebo-controlled RHODOS trial ([1], ClinicalTrials.gov Identifier: NCT00747487) and data from an Expanded Access Program (also part of the post-authorization commitment), which both showed clinically relevant beneficial responses to Raxone in patients with LHON [2]. Treatment benefit manifests as a clinically relevant stabilization (CRS) or a clinically relevant recovery (CRR) of visual acuity or both [3]. The primary objective of the LEROS study was to assess the efficacy of Raxone (150 mg tablets, daily dose of 900 mg) in the promotion of recovery or stabilization of visual acuity (VA) after 12 months. This was evaluated in patients starting treatment up to one year after the onset of symptoms, compared to an external untreated, matched, natural history (NH) control group. The study, conducted in 199 patients, met its pre-specified and agreed primary endpoint and key secondary objectives, including confirmation of its overall favorable safety profile during long-term treatment. After 12 months of treatment, 43.1% of patients treated with Raxone achieved a clinically relevant benefit (CRB) with high statistical significance compared to 20.7% in the NH group (p=0.002; OR [95% CI]: 2.286 [1.352; 3.884]). The clinically relevant beneficial treatment effect was maintained at 24 months compared to the NH group (p=0.0297; OR [95% CI]: 2.082 [1.074; 4.099]). Positive results were also seen after 12 months of treatment in patients starting Raxone treatment >1 year after the onset of symptoms, one of the secondary endpoints, compared to the NH population (p=0.0058; OR [95% CI]: 1.994 [1.219; 3.296]). Santhera conducted the LEROS trial in 31 study sites across nine European countries and the USA.