Phase III trial of GS 010 for treatment of Leber Hereditary Optic Neuropathy. - GenSight.

GenSight Biologics announced topline results from the REVERSE Phase III clinical trial evaluating the safety and efficacy of a single intravitreal injection of GS 010 (rAAV2/2-ND4) in 37 subjects whose visual loss due to 11778-ND4 Leber Hereditary Optic Neuropathy (LHON) commenced between 6 and 12 months prior to study treatment. Topline results further highlight the favorable safety and tolerability profile of GS 010, and demonstrate a clinically meaningful improvement of +11 ETDRS letters (-0.218 LogMAR) in treated eyes at 48 weeks as compared to baseline in all 37 patients.

Unexpectedly, untreated contralateral eyes (treated with a sham injection) show a similar improvement of +11 ETDRS letters (-0.211 LogMAR). Due to this improvement in untreated eyes, the trial did not meet its primary endpoint, defined as a difference of improvement in visual acuity in GS010-treated eyes compared to sham-treated eyes at 48 weeks. The improvement of visual acuity in sham-treated eyes was unexpected based on the natural history of LHON, for which partial spontaneous recovery is reported in only 8 to 22% of patients with the G11778 ND4 mutation (Lam et al. 2014, Riordan-Eva et al. 1995). �This meaningful improvement of untreated eyes observed at week 48 was totally unexpected given what is known and has been published about the natural history of this devastating disease. We will continue to analyze the data to better understand our results, but they suggest that GS 010 benefits both eyes in a way that is still to be understood,� commented Bernard Gilly, Chief Executive Officer of GenSight.

The objectively measured endpoints were the effects of GS 010 on parameters measured with high resolution Spectral-Domain Optical Coherence Tomography (SD-OCT). The critical secondary endpoint of the change in retinal ganglion cell macular volume measured from baseline to week 48 demonstrated a statistically significant difference (p = 0.0189) between all GS 010-treated eyes and all sham-treated eyes, with untreated eyes losing 0.038 cubic mm of macular ganglion cell volume while treated eyes preserved their ganglion cell volume (-0.003 cubic mm). The secondary endpoint of change in thickness of the temporal quadrant and papillomacular bundle of the retinal nerve fiber layer from baseline to week 48 demonstrated a large statistically significant difference (p = 0.0359) between all GS 010-treated eyes and all sham-treated eyes, with untreated eyes showing a loss of 3.4 um while treated eyes showed a limited loss of 0.6 um.