REVERSE Phase III trial of GS 010 shows improvement in Leber Hereditary Optic Neuropathy

GenSight Biologics reported a first set of results from Week 96 of the REVERSE Phase III clinical trial of GS 010 gene therapy in Leber Hereditary Optic Neuropathy (LHON). The trial evaluated 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 commenced between 6 and 12 months prior to study treatment. Week 96 is the last of the scheduled readouts for the trial and marks the time when the data are unmasked, providing access to individual patient profiles. The results point to continued efficacy of GS 010 two years past injection, with best-corrected visual acuity (BCVA) sustaining a clinically meaningful improvement over baseline.

At Week 96, GS 010-treated eyes showed a mean improvement of -0.308 LogMAR compared to baseline, equivalent to +15.4 ETDRS letters or 3 lines on the ETDRS vision chart. This clinically meaningful level of improvement in visual acuity maintains the gain observed at Week 72 (+14.7 ETDRS letters equivalent). As in previous readouts at Week 48 and Week 72, BCVA in sham-treated eyes evolved on a relatively parallel trajectory, achieving a mean improvement of -0.259 LogMAR over baseline, or a gain of +12.9 ETDRS letters equivalent, at Week 96. Although lower in magnitude, the mean BCVA improvement of sham-treated eyes was not statistically significant from that of GS 010-treated eyes. As in RESCUE and consistent with natural history, subjects experienced an initial point of low visual acuity, or nadir. Eyes of REVERSE subjects recovered impressively. By week 96, GS 010-treated eyes had gained +28 more letters relative to their nadir. At Week 96, a second key visual function – low-contrast visual acuity, as measured on the Pelli-Robson chart – showed a similar trend of improvement for both GS 010-treated eyes and sham-treated eyes. The trajectories, however, did not track each other as closely as with BCVA: mean contrast sensitivity for GS 010-treated eyes show a more robust improvement versus baseline over the course of the trial. Nonetheless, the drop in the mean contrast sensitivity of sham-treated eyes was not enough to yield a statistically significant difference in Week 96 mean contrast sensitivity improvement between the two sets of eyes.

Based on a generalized estimating equations (GEE) model, GS 010-treated eyes were 2.8 times more likely to be at or above 20/200 than sham-treated eyes (p = 0.0094). When only eyes that were strictly above the threshold were considered, the odds ratio rose to 3.6 (p = 0.0032).