GenSight Biologics Publishes 5-Year Outcomes for Unilateral LUMEVOQ® Gene Therapy

GenSight Biologics, a clinical-stage biopharmaceutical company, has recently published five-year follow-up data on patients treated with LUMEVOQ® in a renowned medical journal, JAMA Ophthalmology. This study focuses on LUMEVOQ®, an investigational gene therapy designed for treating Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease caused by a mutation in the ND4 gene. The patients involved in the study initially participated in two Phase III trials, RESCUE and REVERSE, and subsequently joined the RESTORE long-term follow-up study.

Key findings from the study highlight that patients treated with LUMEVOQ® demonstrated sustained bilateral improvements in Best-Corrected Visual Acuity (BCVA) over five years, coupled with a favorable safety profile. The therapy's persistent benefits suggest a substantial potential for treating MT-ND4-related LHON. Professor Patrick Yu-Wai-Man, an expert in ophthalmology from the University of Cambridge and lead author of the study, emphasized the significance of these findings, especially in light of the typically poor visual prognosis associated with this specific form of LHON.

RESTORE study participants, assessed two years post-treatment, showed significant improvements in BCVA compared to their lowest recorded levels, known as the nadir. Specifically, LUMEVOQ®-treated eyes improved by an average of 22 ETDRS letters, while sham-treated eyes saw an improvement of 20 letters. This improvement was consistent even five years after the initial treatment. In terms of responder analysis, 66.1% of participants experienced at least a +3 lines improvement in BCVA in at least one eye, with this figure rising to 71.0% when using the criterion of Clinically Relevant Recovery (CRR). By the study's conclusion, an impressive 80.6% of participants had functional vision in at least one eye.

The study also reported positive impacts on patients' quality of life (QoL), as evidenced by the NEI VFQ-25 questionnaire scores, which assess vision-related QoL. Seven out of ten subscale scores demonstrated clinically significant improvements, with the composite score showing a meaningful gain of seven points from baseline. Safety assessments over the five-year period confirmed that LUMEVOQ® is well-tolerated, with most ocular adverse events being mild and no severe or serious cases reported.

The RESTORE study is notable for being one of the largest long-term follow-up studies for a rare disease treatment, with 62 participants enrolled. The study involved administering a single intravitreal injection of LUMEVOQ® in one eye and a sham injection in the other.

GenSight Biologics, headquartered in Paris, is committed to developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. Their pipeline is anchored in two core technology platforms, Mitochondrial Targeting Sequence (MTS) and optogenetics, aimed at preserving or restoring vision in patients with blinding retinal conditions. LUMEVOQ® (GS010), their leading product candidate, leverages MTS technology to address mitochondrial defects in LHON, using an AAV vector to deliver the therapeutic gene directly into cells.

Leber Hereditary Optic Neuropathy (LHON), a maternally inherited genetic condition, leads to the degeneration of retinal ganglion cells, causing sudden and severe vision loss, primarily affecting teens and young adults. The disease is characterized by its symmetric nature, with the second eye often becoming impaired shortly after the first, leaving patients with limited options for functional visual recovery. GenSight Biologics’ gene therapy approach offers a single-treatment solution aimed at providing lasting visual recovery for those affected by this debilitating condition.