GenSight Biologics announced publication of detailed results from the phase 1/2 clinical trial and long-term follow-up of GS010 in Leber Hereditary Optic Neuropathy (LHON) patients in Ophthalmology. The study demonstrated that GS010 (rAAV2/2-ND4) is safe and well tolerated 2 years after a single unilateral intravitreal administration.
“This first-ever scientific publication of clinical data with GS010 is a major step forward for patients afflicted with LHON – a blinding disease affecting those in the prime of their life,” Dr. Catherine Vignal, investigator of the study and Chief of the Department of Ophthalmology at the Rothschild Foundation Hospital in Paris, said in a company news release. “If these promising results are confirmed in the ongoing phase 3 studies, GS010 would offer a meaningful and life changing therapy for those so afflicted and become the standard of care for LHON.”
The study was an open-label single-center phase 1/2 clinical trial that included 4 dose-escalation cohorts and an extension cohort. Fifteen subjects with LHON carrying the ND4-G11778A mutation were prospectively enrolled. Each subject received a single intravitreal injection of rAAV2/2-ND4 in the worse-seeing eye. The study design included an initial follow-up period of 48 weeks, followed by longer-term follow-up for an additional 4 years. The primary objective was the safety and tolerability of escalating doses of rAAV2/2-ND4. Secondary objectives included bio-dissemination and immunogenicity of rAAV2/2-ND4 and evaluation of visual functions.
At week 96, there were no unexpected TEAEs, no serious adverse events related to the treatment or procedure, and no suspected unexpected serious adverse reactions. No deaths and no TEAEs leading to study discontinuation were reported. 94% of TEAEs were mild in intensity. The most frequent ocular TEAEs were intraocular inflammation and IOP elevation. All ocular events resolved spontaneously or after appropriate therapy with IOP-lowering or anti-inflammatory therapy, except for 1 subject with ongoing mild vitritis (0.5+ vitreous cell, no vitreous haze, no treatment required at last visit), subsequently lost to follow-up but without documented worsening of vision. At week 96, no related TEAEs required ongoing treatment.
GenSight Biologics is currently conducting two phase 3 clinical studies (RESCUE and REVERSE) in Europe and the United States to assess the efficacy of GS010 in subjects affected with LHON due to the ND4 mutation, with vision loss up to 1 year at the time of treatment. Topline results at 48 weeks for REVERSE and RESCUE are expected in April 2018 and the third quarter of 2018, respectively.
The publication entitled “Safety of rAAV2/2-ND4 Gene Therapy for Leber Hereditary Optic Neuropathy” is available online (www.aaojournal.org/article/S0161-6420(17)33673-4/fulltext) and is in press for Ophthalmology.
Part of this data will also be presented at the North American Neuro-Ophthalmology Society (NANOS) conference in Big Island, Hawaii, March 3–8, 2018 and the Association for Research in Vision and Ophthalmology (ARVO) conference to be held in Honolulu, Hawaii, April 29 to May 3, 2018.