GenSight Biologics Reveals Five-Year LUMEVOQ® Gene Therapy Results from REFLECT Study

GenSight Biologics, a biopharmaceutical company specializing in innovative gene therapies for retinal diseases and central nervous system disorders, recently unveiled the final results from the REFLECT Phase III clinical trial concerning their gene therapy product, LUMEVOQ® (GS010; lenadogene nolparvovec). These results, presented in February 2025, highlight a sustainable improvement in visual acuity among patients suffering from Leber Hereditary Optic Neuropathy (LHON) five years post-treatment, with the therapy maintaining a favorable safety profile.

The REFLECT trial aimed to assess the long-term efficacy and safety of LUMEVOQ®, focusing on patients who received either bilateral or unilateral injections. The findings confirmed that visual acuity improvements were consistent over five years, with bilateral injections providing an added benefit over unilateral treatment. In particular, patients who received treatment in both eyes exhibited a higher rate of clinically meaningful recovery compared to those treated in just one eye. This was significant, given that LHON typically results in severe vision impairment with minimal chance of spontaneous recovery.

One of the primary measures used in the study was Best-Corrected Visual Acuity (BCVA), which highlighted that all LUMEVOQ®-treated eyes demonstrated improvement beyond the clinically meaningful threshold of a +15-letter increase. This improvement was evident despite the severe acute phase of LHON, where vision often deteriorates significantly early in the disease's progression. Bilaterally treated patients saw a higher percentage (79%) achieving on-chart vision, compared to 72% for those treated unilaterally.

Safety assessments revealed a favorable profile for LUMEVOQ®, with no discontinuations due to systemic or ocular adverse events. The most common ocular adverse event was mild intraocular inflammation, which responded well to conventional treatments. These findings were consistent across both bilaterally and unilaterally treated groups, reinforcing the safety of LUMEVOQ® over an extended period.

The REFLECT trial was a robust, multi-center, randomized, double-masked, placebo-controlled study involving 98 subjects with LHON caused by mutations in the ND4 mitochondrial gene. Participants received an intravitreal injection of lenadogene nolparvovec in their first affected eye. Subsequently, the second affected eye was either treated with another dose of LUMEVOQ® or a placebo, with the choice being randomized. Of the 98 subjects, 48 received bilateral treatment, while 50 underwent unilateral treatment. The trial’s efficacy endpoints centered around changes in BCVA and other vision-related measures at various intervals post-treatment. The study spanned several international centers and concluded with long-term follow-up in July 2024.

In summary, the REFLECT trial's results underscore the potential of LUMEVOQ® as a significant therapeutic option for those afflicted by LHON. The sustained improvement in visual outcomes and the therapy's solid safety profile offer hope for individuals grappling with this rare and debilitating condition. GenSight Biologics continues to advance its pipeline of gene therapies, leveraging cutting-edge technologies to address unmet needs in retinal and central nervous system disorders.