GenSight Biologics

Key Opinion Leaders Highlight GS010 Efficacy and Patient Benefits in Discussion of Findings from REVERSE Phase III Clinical Trial - Seite 2

For Dr. Sergott, REVERSE results combined for the first time “evidence on preserved retinal anatomy with evidence on improved visual function”:

• At week 48, there was a statistically significant difference (p = 0.0189) between the change in retinal ganglion cell macular volume measured from baseline compared to 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).
• In terms of the change in thickness of the temporal quadrant of the retinal nerve fiber layer from baseline to week 48, the trial demonstrated a large statistically significant difference (p = 0.0359) between all GS010-treated eyes and all sham-treated eyes, with untreated eyes showing a loss of 3.4 μm while treated eyes showed a limited loss of 0.6 μm.
• At week 48, GS010 treated eyes gained on average +0.20 LogCS, while the contrast sensitivity in sham-treated eyes remained stable (+0.08 LogCS on average). This difference was statistically significant, with a p-value of p = 0.0220.

Dr. Sergott acknowledged the topline finding that, at 48 weeks, there was no statistical difference between GS010-treated and sham-treated eyes in terms of improvement in high-contrast visual acuity, as measured by logMAR acuity. However, he pointed out that the timing and magnitude of the observed improvement in each eye were at odds with known facts of LHON natural history.

Dr. Moster, after reviewing published literature on the disease’s natural history, had remarked, “Spontaneous recovery can occur, but only in a small subset of patients. And among the mutations that cause LHON, this phenomenon is rarest among patients with the 11778 mutation, which is the one targeted by GS010.” He further highlighted that the instances of recovery tended to occur more than 20 months after vision is lost.

Dr. Sergott further asserted, “It is a fallacy to consider the bilateral improvement a placebo effect.” In his discussion, Dr. Sahel explained that while a definitive explanation for the bilateral effect is still lacking, a number of hypotheses can be advanced based on observations in other disease areas and on animal models of ocular injury. Improvement in the contralateral eye is not without scientific precedent.

Dr. Sergott shared trends from post hoc analyses that, consistent with the progressive nature of LHON, support the notion that earlier intervention resulted in better clinical outcomes: