RESCUE Phase III trial of GS 010 failed to meet primary endpoint in Leber Hereditary Optic Neuropathy.- GenSight Biologics

GenSight Biologics announced results from the first scheduled readout, at Week 48, of the RESCUE Phase III clinical trial evaluating the safety and efficacy of a single intravitreal injection of GS 010 (rAAV2/2-ND4) in 39 subjects whose visual loss due to 11778-ND4 Leber Hereditary Optic Neuropathy (LHON) occurred up to 6 months prior to study treatment. These subjects received GS 010 in one eye and a sham injection in the other eye, with drug treatment randomized between best- and worst-affected eyes. Visual loss in LHON usually progresses such that vision reaches a nadir in 3 to 5 months, before stabilizing; the duration of this progression to nadir varies from patient to patient.

In RESCUE, mean best-corrected visual acuity (BCVA) of GS 010-treated eyes and sham-treated eyes evolved with similar trajectories, worsening to a low point before showing an improvement at Week 48. At Week 48, change from baseline for GS 010-treated eyes was -19 ETDRS letters equivalent, while that for sham-treated eyes -20 ETDRS letters equivalent. These figures incorporate a recovery from the nadir of vision loss for drug- and sham-treated eyes: mean improvement over the nadir of vision loss was +13 ETDRS letters equivalent in GS 010-treated eyes and +11 ETDRS letters equivalent in sham-treated eyes. The primary efficacy endpoint, defined as a +15-letter difference in visual acuity improvement for GS 010-treated eyes compared to sham-treated eyes at 48 weeks, was not met. Planned analysis of other visual functions and anatomic measures showed results broadly consistent with the direction of BCVA evolution: similar trajectories for GS 010-treated and sham-treated eyes with the difference in change from baseline not being statistically significant at Week 48. The difference between GS 010-treated and sham-treated eyes in change from baseline of temporal retinal nerve fiber layer missed statistical significance.

The changes from baseline in GS 010-treated eyes of papillo-macular bundle thickness and ganglion cell volume were numerically superior to those in sham-treated eyes, though not statistically significant. Even at an early readout at Week 48, some trends point toward GS 010 efficacy. GS 010-treated eyes were significantly more likely than sham-treated eyes to have 20/200 or better vision, the threshold for legal blindness (statistically significant). GS 010 was reported to be safe and well-tolerated.