22 July 2022 - - French biopharma company GenSight Biologics (PAR: SIGHT) (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible) has reported that after five years of follow-up, Leber Hereditary Optical Neuropathy subjects treated with Lumevoq (GS010) continued to experience significantly improved vision as a result of a one-time injection of the gene therapy treatment.

Compared to the trend in vision observed among untreated patients1, the findings are a significant divergence from the natural outcomes of LHON.

The data from RESTORE (CLIN06)2, the long-term follow-up study to which all participants in the RESCUE3 and REVERSE4 Phase III pivotal trials were invited, also continue to show that the treatment is well-tolerated over the five-year follow-up period.

5 years' data on efficacy and safety shows substantial durability evidence and is more extensive than what is typically submitted in a data package for a gene therapy.

When RESTORE subjects enrolled in the study two years after the one-time injection, they had already experienced clinically meaningful improvements relative to the lowest point of their best-corrected visual acuity : +18.8 ETDRS letters equivalent in their Lumevoq -treated eyes and +17.3 letters equivalent in their sham-treated eyes.

Five years after treatment, the bilateral improvement from nadir was sustained, with Lumevoq-treated eyes achieving a mean improvement against nadir of +22.0 letters equivalent and sham-treated eyes demonstrating a mean improvement of +19.5 letters equivalent.

The impact of such results on patients is demonstrated by increases in the self-reported quality of life scores at Year 5 vs. baseline.

Mean overall QoL increased by a clinically meaningful magnitude relative to baseline, driven by increases in the sub-scores corresponding to mental health and the ability to carry out activities autonomously (e.g., composite score, mental health, role difficulties, dependency, near and distance activities, general vision, social functioning).

RESTORE is a large long-term follow-up study for a rare disease treatment, with 62 subjects accepting the invitation to enroll and 55 completing the study.

All subjects, who were affected by LHON caused by a mutated ND4 mitochondrial gene, were treated with an intravitreal injection of LUMEVOQ in one eye and with sham injection in the other.

Responder analyses at Year 5 indicate that improved BCVA was a benefit for a substantial proportion of the study participants. 71.0% of RESTORE subjects achieved Clinically Relevant Recovery 5 against nadir 5 years after treatment, and 80.7% of them had on-chart vision (BCVA ≤ 1.6 LogMAR) in one or both eyes.

Safety findings at five years post-injection were consistent with previous readouts, which concluded that Lumevoq is well-tolerated: no serious adverse events were recorded among Lumevoq-treated eyes, and no discontinuations occurred due to ocular events.

There were no systemic serious adverse events or discontinuations related to study treatment or study procedure.

The review of the European Marketing Authorisation Application for Lumevoq is ongoing, with the decision from the CHMP expected in 3Q23 as a result of an extension granted by the EMA for GenSight's responses to its Day 120 questions. Commercial launch will follow approval by the end of 2023.

GenSight Biologics S.A. is a clinical-stage biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders.

The company's pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases.

GenSight Biologics' lead product candidate, GS010, is in Phase III trials in Leber Hereditary Optic Neuropathy, a rare mitochondrial disease that leads to irreversible blindness in teens and young adults.