Presenting results from the initial Phase I/II mitochondrial gene therapy for ND4 Leber’s hereditary optic nerve (LHON), GenSight’s Barrett Katz, MD, chief medical officer, stressed that LHON is not Leber’s congenital amaurosis, and there are different targets for each.
In LHON, about 75% of those affected in North America and the European Union have a mutation on 11778-ND4. LHON is considered the most common inherited mitochondrial disease. GenSight is using rAAV2/2-ND4 to replace the defective gene. “These patients live with this genetic defect for several decades before waking up blind one day,” Katz said. The blindness is usually unilateral, but within two months the person is bilaterally blind.
Topline results from GenSight’s Phase III study of GS010 are expected in 2018, but there seems to be a “signal of efficacy” and a “high delta” at weeks 26, 48, and 96 between treated and untreated eyes in the dose escalation study. At week 96, there were no adverse events and no vision loss. “There is a window of opportunity to protect the second eye,” Dr. Katz said. To date, the Phase III RESCUE study (evaluating those with <6 months of vision loss) and REVERSE study (vision loss >6 months to <12 months) are fully enrolled (n=76). GenSight expects to file for marketing authorization in 2019.