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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

GenSight Biologics’ retinal gene therapy fails to meet primary endpoint

GenSight Biologics has announced interim results of its RESCUE study, a Phase 3 clinical trial designed to evaluate a single intravitreal injection of GS010 in the treatment of Leber’s Hereditary Optic Neuropathy (LHON). Although the treatment was safe and tolerable, the study did not meet the primary end point at 48 weeks.

LHON is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent and severe bilateral loss of visual acuity within weeks or months. The disease is caused by the G11778A mutation in the mitochondrial ND4 gene. GenSight’s GS010 uses a mitochondrial targeting sequence proprietary technology platform which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an adeno-associated vector.

RESCUE trial is designed to evaluate the safety and efficacy of a single intravitreal injection of GS010 in subjects affected by LHON with < 6 months of onset of vision loss. Latest results from the trial showed a favourable safety and tolerability profile for GS010 at 48 weeks and there were no serious ocular adverse events or discontinuations due to ocular issues. Mean best-corrected visual acuity (BCVA) among GS010-treated eyes and sham-treated eyes evolved with similar trajectories, worsening to a low point, before beginning to improve by week 48. However, the study did not meet the primary end point like as in the REVERSE trial, which was defined as +15-letter difference in visual acuity improvement for GS010-treated eyes compared to sham-treated eyes at 48 weeks. Clinically meaningful improvement of +13 ETDRS letters was observed in GS010-treated eyes and +11 ETDRS letters in sham-treated eyes at 48 weeks compared to baseline in all subjects.

GenSight Biologics is a Paris-based clinical-stage biotechnology company focusing on developing gene therapies for retinal diseases and diseases of the central nervous system. Other than the RESCUE trial, GS010 is currently being investigated in two additional Phase 3 trials: REVERSE and REFLECT. REVERSE is a randomized, double-masked, sham-controlled, multi-center trial conducted in 37 patients with an onset of vision loss of 6-12 months. REFLECT is evaluating the safety and efficacy of bilateral injections of GS010 in patients with < 1 year of onset of vision loss in LHON.

The result has come as a surprise for GenSight and they think that the rapid degeneration of neurons early in the disease combined with the time needed for GS010 to start functioning might be the reason for not seeing a positive effect at 48 weeks. The subjects will be evaluated again at later time points, 72 and 96 weeks and results are expected to be available later this year.

Dr. Barrett Katz, GenSight’s CMO commented: “In our REVERSE trial, which included patients with vision loss between 6 and 12 months prior to treatment, we saw more improvement in both anatomic measures and visual functions as the disease entered its chronic phase. The planned readouts of RESCUE data at Weeks 72 and 96 should confirm GS010’s efficacy.”

Source: GenSight Biologics reports topline results at Week 48 of the RESCUE Phase III clinical trial of GS010 in subjects within six months of visual loss onset due to Leber Hereditary Optic Neuropathy (LHON)