Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects With Leber's Hereditary Optic Neuropathy: A Randomized Trial

Purpose The purpose of this study was to assess the safety, tolerability, and potential efficacy of topical elamipretide in patients affected with Leber’s Hereditary Optic Neuropathy (LHON). Design This Phase 2, prospective, randomized, vehicle controlled, single-center clinical trial involved administration of elamipretide (MTP-131) topical ophthalmic solution to LHON patients over a 52-week double-masked treatment period (DMTP), followed by an open extension label (OLE) for up to 108 additional weeks of treatment. Subjects Twelve patients affected with LHON were included in this study. Patients between ages 18 and 50 with decreased vision, for at least one year and no more than ten years, and a genetically confirmed diagnosis of m.11778G>A LHON were eligible for this trial. Methods For the first 52 weeks of the study, patients were randomized to one of two arms, elamipretide in both eyes or elamipretide in one eye and vehicle in the other eye, followed by an OLE where both eyes were treated with elamipretide. Main outcome measures The primary outcome measure was the assessment of adverse events from the administration of topical elamipretide 1% and the primary efficacy endpoint was change in best corrected visual acuity (BCVA). Secondary outcome measures included changes in color vision, visual field mean deviation, and electrophysiological outcomes. Results Elamipretide was well tolerated with the majority of treatment-emergent adverse events (TEAEs) being mild to moderate and resolving spontaneously. The change from baseline in BCVA in elamipretide-treated eyes was not significantly different from the vehicle eyes at any time point. Six of 12 subjects met the criteria for clinically relevant benefit (CRB). In the post-hoc analysis, change from baseline in mean deviation in the central visual field was significantly greater in elamipretide treated eyes versus the vehicle eyes. Compared to baseline, both treatment groups showed improvement in color discrimination and contrast sensitivity in the OLE. Conclusions Elamipretide treatment was generally well tolerated with no serious adverse events reported. Although this study did not meet its primary BCVA efficacy endpoint, improvements across assessments on visual function during the OLE, and the post-hoc findings of the HVF central region, were encouraging and require further exploration.