GenSight Biologics Announces Publication of 5-Year Outcomes for Patients Treated Unilaterally with LUMEVOQ® Gene Therapy

Paris, France, Wednesday, January 15, 2025, 7:30 am CET – GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced the publication of outcomes data from five years’ follow-up of patients treated unilaterally with LUMEVOQ^®, the company’s investigational gene therapy for Leber Hereditary Optic Neuropathy (LHON) due to a mutated ND4 mitochondrial gene. The patients had all participated in the Phase III trials RESCUE and REVERSE and accepted enrolling into the long-term study RESTORE at the end of the RESCUE and REVERSE studies.

The paper, published online by the leading journal JAMA Ophthalmology in December 2024, found that patients “demonstrated a sustained bilateral improvement in BCVA [Best-Corrected Visual Acuity] and a good safety profile over 5 years after treatment”. The “persistent benefit” continues the durable effect observed at earlier time points and represents a significant addition to the body of evidence on the benefit-risk ratio of LUMEVOQ^® gene therapy in ND4 LHON patients.

“The findings on the persistence of visual improvement show the promise of using LUMEVOQ gene therapy to treat patients with LHON due to the MT-ND4 gene variant,” noted Prof. Patrick Yu-Wai-Man, MD, PhD, Professor of Ophthalmology and Honorary Consultant Neuro-ophthalmologist at the University of Cambridge, Moorfields Eye Hospital, and the UCL Institute of Ophthalmology, United Kingdom, lead author and Principal Investigator in the RESCUE, REVERSE and RESTORE studies. “The results are especially encouraging given the poor visual prognosis of MT-ND4 LHON, which is the most frequent and severe clinical form of this rare mitochondrial genetic disease.”

When RESTORE participants enrolled in the study, 2 years after the one-time injection, they had already experienced clinically meaningful improvement relative to the lowest point (the “nadir”) of their Best-Corrected Visual Acuity (BCVA): +20 ETDRS letters equivalent in their LUMEVOQ^®-treated eyes and +17 ETDRS 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 letters equivalent and sham-treated eyes demonstrating a mean improvement of +20 letters equivalent.

Table 1. Change in BCVA Vs. Nadir^* In LUMEVOQ^® Long-Term Follow-Up (RESTORE)

SD: Standard Deviation. Imputed data in alignment with the statistical analysis plan. Figures in this table were extracted from eTable 2 of the article. The RESTORE sample consists of the RESCUE and REVERSE participants who accepted to be followed in the long-term follow-up study. *Nadir = worst best-corrected visual acuity recorded from baseline to time point of interest. **Assessments of best-corrected visual acuity (BCVA) were recorded in LogMAR. The change from nadir in LogMAR was converted to “letters equivalent” improvement by multiplying the LogMAR by -50 (ref. J.T. Holladay, J Refrac Surgery, 1997;13, 388-391).

Responder analyses at Year 5 indicate that improved BCVA was a benefit for a substantial proportion of the study participants. 66.1% of RESTORE participants achieved clinically meaningful (at least +3 lines’ improvement) from nadir in at least one eye, and the proportion rises to 71.0% if the criterion used is Clinically Relevant Recovery (CRR)¹ against nadir. At the end of the five-year follow-up period, 80.6% of participants had on-chart vision (BCVA ≤ 1.6 LogMAR) in at least one eye.

The impact of such results on patients is demonstrated by increases in the self-reported quality of life (QoL) scores at Year 5 vs. baseline. Clinically significant improvement from baseline was observed in 7 of 10 subscale scores of the NEI VFQ-25 questionnaire used to assess quality of life. The composite score showed a clinically meaningful gain of 7 points from baseline.

Safety findings at 5 years post-injection were consistent with previous readouts, which concluded that LUMEVOQ^® is well-tolerated. The systemic safety was excellent and most ocular events were mild, none were severe or serious, and none led to study discontinuation.

RESTORE is one of the largest long-term follow-up studies for a rare disease treatment, with 62 participants accepting the invitation to enroll. All participants were treated with a single intravitreal injection of LUMEVOQ^® in one eye and with sham injection in the other.

The full article is available online on this link.

Definition:

1. Clinically Relevant Recovery (CRR) corresponds to an improvement of at least 0.2 LogMAR (for on-chart eyes) or a movement from off-chart to on-chart (for off-chart eyes).