GenSight Biologics Announces Groundbreaking 5-Year Outcomes for Unilateral LUMEVOQ® Gene Therapy
GenSight Biologics (Euronext: SIGHT) has announced the publication of five-year follow-up data for patients treated with its investigational gene therapy, LUMEVOQ® (lenadogene nolparvovec), for Leber Hereditary Optic Neuropathy (LHON). The study focused on participants from the Phase III RESCUE and REVERSE trials who later enrolled in the long-term RESTORE study. The results, published online in JAMA Ophthalmology in December 2024, show that patients who received a single intravitreal injection of LUMEVOQ® experienced sustained visual improvements over the five-year period, while maintaining a favorable safety profile.
LUMEVOQ® targets LHON caused by mutations in the ND4 mitochondrial gene, a rare, progressive disease that leads to irreversible blindness, primarily affecting young adults. The five-year data confirms that LUMEVOQ® continues to provide durable improvements in visual acuity, preserving the benefits seen in earlier follow-ups. This ongoing positive impact reinforces the growing body of evidence supporting LUMEVOQ® as a promising treatment for ND4 LHON.
Professor Patrick Yu-Wai-Man, the lead author of the study and a key investigator in the RESCUE, REVERSE, and RESTORE trials, emphasized the importance of the findings. “The continued visual improvement highlights the potential of LUMEVOQ® gene therapy for treating LHON caused by the MT-ND4 gene variant,” said Prof. Yu-Wai-Man, who also holds positions as a Professor of Ophthalmology at the University of Cambridge and a Consultant Neuro-ophthalmologist at Moorfields Eye Hospital. “Given the poor prognosis for MT-ND4 LHON, the most common and severe form of this disease, these results are particularly encouraging.”
The RESTORE study, which followed participants for two years after their initial treatment, found that those who received LUMEVOQ® showed a meaningful improvement in Best-Corrected Visual Acuity (BCVA) compared to their lowest recorded visual acuity (nadir). Two years post-treatment, LUMEVOQ®-treated eyes saw an improvement of +20 ETDRS letters, while sham-treated eyes improved by +17 letters. At five years, the improvement remained consistent, with LUMEVOQ®-treated eyes showing a +22 letter improvement and sham-treated eyes showing a +20 letter improvement from nadir.
The study also evaluated the proportion of patients who achieved clinically meaningful improvements. At five years, 66.1% of participants showed at least a +3 lines improvement in BCVA in one eye, and 71.0% met the criteria for Clinically Relevant Recovery (CRR). Notably, 80.6% of patients had on-chart vision (BCVA ≤ 1.6 LogMAR) in at least one eye at the five-year mark.
Patients also reported improvements in their quality of life, with 7 out of 10 subscale scores on the NEI VFQ-25 questionnaire showing clinically significant improvements compared to baseline. The overall composite score increased by 7 points, indicating enhanced daily functioning and vision-related quality of life.
Safety data from the five-year follow-up showed that LUMEVOQ® was well tolerated by participants. Most ocular adverse events were mild, and none were severe or led to discontinuation of the study. The systemic safety profile was also excellent, further supporting the treatment’s overall safety.
The RESTORE study is one of the largest long-term follow-up studies for a rare disease treatment, enrolling 62 participants who received a single intravitreal injection of LUMEVOQ® in one eye and a sham injection in the other. This study has provided valuable insights into the long-term effects and safety of LUMEVOQ® for treating ND4 LHON.
About GenSight Biologics
GenSight Biologics is a clinical-stage biopharmaceutical company focused on developing innovative gene therapies for retinal diseases and central nervous system disorders. The company’s pipeline includes GS010 (LUMEVOQ®), a gene therapy targeting LHON, currently in Phase III trials. GenSight’s gene therapy-based treatments are designed to offer sustainable vision restoration with a single injection.
About Leber Hereditary Optic Neuropathy (LHON)
LHON is a rare, maternally inherited mitochondrial disease that causes rapid and irreversible loss of central vision, primarily affecting adolescents and young adults. It leads to degeneration of retinal ganglion cells, resulting in blindness. The disease typically progresses symmetrically, affecting both eyes within a year of the initial vision loss.
About LUMEVOQ® (GS010)
LUMEVOQ® (GS010) is a gene therapy designed to treat LHON by delivering a corrected version of the ND4 gene directly to retinal cells using a mitochondrial-targeted adeno-associated virus (AAV) vector. Administered via a single injection in each eye, it offers a potential solution for restoring vision in patients with this devastating condition.
About the RESCUE, REVERSE, and RESTORE Trials
RESCUE and REVERSE were Phase III, randomized, double-masked, sham-controlled trials assessing the efficacy of GS010 in LHON patients with the G11778A mutation in the ND4 gene. Both trials demonstrated the therapy’s ability to significantly improve BCVA compared to sham treatment. After completing these trials, participants were invited to join the RESTORE study, a long-term follow-up study designed to assess the safety, efficacy, and quality of life for up to five years post-treatment. GenSight’s dedication to advancing research for LHON treatment is evident in the ongoing progress of these trials.
