GenSight Biologics reported results from the REALITY registry study and an analysis of REVERSE and RESCUE phase 3 data, which further highlight the poor prognosis for patients with loss of vision due to Leber Hereditary Optic Neuropathy (LHON) associated with the ND4 mutation. The results confirm LHON experts’ observations from their clinical practice and contrast sharply against the bilateral improvement observed in Lumevoq (GS010)’s phase 3 studies.
“Natural history studies in LHON have been difficult to conduct, so these results add to the body of knowledge and firm up the conventional wisdom that with rare exceptions, LHON is marked by precipitous loss of vision with little chance of improvement in the first few years,” Mark Moster, MD, Neuro-Ophthalmology, Wills Eye Hospital and Professor of Neurology and Ophthalmology at Thomas Jefferson University, Philadelphia, and investigator in the REVERSE and RESCUE trials, said in a company news release. “The lack of improvement in the REALITY subjects is in stark contrast to the improvements seen in our REVERSE and RESCUE patients.”
REALITY is a retrospective and cross-sectional observational study of subjects with LHON, conducted in centers across Spain, Italy, France, United Kingdom, and the United States. The objective is to generate insights about the natural history of the disease based on an approach that would facilitate comparisons with REVERSE and RESCUE. The study seeks to enroll 50 subjects by the second quarter of 2020.
Interim analysis of REALITY, based on the 15 subjects with the ND4 mutation who were at least 15 years old at onset and who had enrolled in the study as of September 2019, shows the dramatic and usually irreversible decline in visual acuity that is the typical outcome for ND4 LHON patients. Unlike in subjects enrolled in REVERSE and RESCUE, who all received a unilateral injection of Lumevoq, mean visual acuity in REALITY subjects did not recover after the initial decline.
“These findings highlight just how remarkable the visual trends in REVERSE and RESCUE are,” said Bernard Gilly, Co-founder and Chief Executive Officer of GenSight. “The findings will support our effort to provide regulatory authorities with the most robust insights about the natural history of the disease, so that we can convincingly demonstrate the therapeutic benefit delivered by Lumevoq.”
A second set of results, derived from a pooled dataset of baseline readings from the REVERSE and RESCUE patient populations, shows that eyes farther along the progression of the disease, as measured by time since onset, had worse visual acuity.
The picture of visual decline is based on cross-sectional data, yet remains consistent with the pattern revealed by the interim analysis for REALITY.