EPI-743 (Quinone) therapy for Leber’s Hereditary Optic Neuropathy: the Brazil experience.

Abstract

Purpose : To determine the degree of visual improvement, using markers of visual function, in a homogeneous Brazilian cohort of Leber’s Hereditary Optic Neuropathy (LHON) 11778 receiving up to 52 months of therapy with a novel quinone.

Methods : As part of an open label trial, six Brazilian, LHON patients experiencing significant visual loss were offered an experimental therapeutic, alpha-tocotrienol quinone (EPI-743). Two acute patients receiving EPI-743 during acute visual decline and four patients had chronic disease (>5 years) at the start of therapy. Snellen visual acuity (VA) in logMAR represented best correct vision. We utilized an algorithm developed by the University of Iowa Visual Field Reading Center that derives mean deviations (MD) from raw numerical data of STIM III and STIM V Humphrey Visual Fields (HVFs) to obtain participants’ visual field MDs. A change of +5 db was considered an improved HVF. Retinal nerve fiber layer (RNFL) thickness was measured using time (2007-2009) or spectral (2010-2015) domain Optical Coherence Tomography (OCT).

Results : The two patients who were treated at time of conversion showed continued bilateral progressive loss of vision for the first 6 months, consistent with the natural history of LHON. VA declined or stabilized in the first year of therapy in all patients. Due to issues with agent access, one acute and two chronic patients chose to withdraw from the study. The observed improvement in VA was stable for up to 52 months of EPI-743, though there was a small VA decline after the withdrawal of therapy in those patients who discontinued therapy. HVF improved (>5 dB) in one chronic and both acute patients, while three chronic patients remained stable. HVF remained stable after the withdrawal of therapy in those patients who chose to withdraw from the study. As expected, all eyes showed reductions in RNFL on OCT that eventually stabilized on therapy, not inconsistent from the natural history of the disease.

Conclusions : The visual acuity improvements begun in the first 12 months of EPI-743 described in our previous ARVO abstract, continued for 36-52 months of treatment; remarkably this included even in subjects who had converted over 5 years prior to the initiation of treatment.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.