ИСТИНА

isclosure Block: Tatiana Nevinitsina, FGBNU Naucno-issledovatel'skij institut glaznyh boleznej (E); Natalia Sheremet, None; Natalia Andreeva, None; Nino Zhorzholadze, None; Irina Ronzina, None; Konstantin Lyamzaev, None; Tatiana Krylova, None; Polina Tsygankova, None; Maxim Skulachev, Moskovskij gosudarstvennyj universitet imeni M V Lomonosova Naucno-issledovatel'skij institut fiziko-himiceskoj biologii imeni A N Belozerskogo (E); Elena Karger, Moskovskij gosudarstvennyj universitet imeni M V Lomonosova Naucno-issledovatel'skij institut fiziko-himiceskoj biologii imeni A N Belozerskogo (E); Anton Petrov, Mitotech S.A. (E) Purpose: This observational clinical study was designed to assess the effects of mitochondrial reactive oxygen species (mtROS) scavenger Visomitin (SkQ1 ophthalmic solution) in Leber hereditary optic neuropathy (LHON) patients relative to data demonstrated by prior natural history studies of disease progression and to identify potential primary endpoints for a future double-blind, randomized, placebo-controlled study. Methods: This was an uncontrolled, open-label, observational study, comprising 6 visits over the course of 30 months. 43 subjects diagnosed with mitochondrial optic neuropathy who were prescribed Visomitin (0.155ug/mL SkQ1 Ophthalmic Solution) for Dry Eye Disease were observed. 26 patients (24 men and 2 women) had genetically confirmed LHON-related mutations in mtDNA. There was no designated primary endpoint. Best Corrected Visual Acuity was assessed using Freiburg Vision Test for low vision. Results: All 26 subjects with LHON-related mtDNA mutations completed the initial 12-month observation period. Average BCVA of LHON patients significantly improved by 0.37 logMAR (p=2x10-8) relative to baseline after 12 months. After 30 months of treatment BCVA change from baseline was 0.42 logMAR (p=1x10-10). According to the International Consensus, BCVA improvement of 2 lines (0.2 logMAR) is considered clinically relevant in LHON patients. Studies of natural history of LHON patients carrying the m.11778G>A mutation suggest that over a comparable time frame, BCVA improvement of 0.3 logMAR or more occurs in 18% of patients, and the deterioration of BCVA of the same value (0.3) occurs in 14%. In this study, among patients with m.11778G>A mutation treated with Visomitin an improvement by 0.3 logMAR and more was observed in 56% of patients by the end of the study, while deterioration by 0.3 LogMAR or more was not observed. Conclusions: Visomitin ophthalmic solution, a drug designed for protection of ocular tissue from oxidative stress at mitochondrial level, demonstrated statistically significant improvement of BCVA relative to baseline in LHON patients. These improvements compare favorably when considering the typical natural history of disease progression. These findings warrant design of a double-masked, randomized, placebo-controlled study of Visomitin efficacy in LHON patients.