GenSight Biologics announced that a phase 3 study investigating a single injection of the experimental gene therapy GS010 failed to improve vision loss compared to sham treatment in patients with 11778-ND4 Leber hereditary optic neuropathy (LHON).
In the RESCUE study, patients with LHON were assigned to receive a single injection of GS010 in one eye, while the second eye received sham treatment. The trial’s primary endpoint was a 15-letter difference in visual acuity improvement for GS010-treated eyes versus sham-treated eyes.
Topline results showed that GS010 was not associated with improvements in the evolution of mean best-corrected visual acuity versus sham treatment after 48 weeks. Findings also revealed no significant difference between GS010-treated and sham-treated eyes regarding the change versus baseline in the temporal retinal nerve fibre layer. Meanwhile, although the changes from baseline in the papillo-macular bundle thickness and ganglion cell volume were numerically superior for GS010-treated eyes, statistical significance was not achieved.
Commenting on the data, José-Alain Sahel, co-founder of GenSight, remarked “the powerful and rapid degeneration of neurons early in the disease, combined with the time needed for GS010 to cause functioning proteins to be expressed, may be confounding efficacy measurements early in the active progression phase.”
GenSight noted that in the study, GS010-treated eyes were more likely to have at least 20/200 vision, while responder analysis indicated that 24 percent of patients experienced an at least 15-letter improvement in high-contrast visual acuity from baseline in the GS010-treated eye. Additionally, 24 percent of responders also displayed at 15-letter or better improvement in low-contrast acuity from baseline in the GS010-treated eye.
In April last year, GenSight said that the similar phase III REVERSE study of GS010 in patients with LHON failed to meet its primary endpoint, with sham-treated eyes demonstrating similar improvements in vision compared to the gene therapy. Chief medical officer Barrett Katz noted that in the REVERSE trial, improvements were seen “in both anatomic measures and visual functions as the disease entered its chronic phase,” adding the planned readouts of RESCUE data at weeks 72 and 96 should confirm GS010’s efficacy.”