Long-term Efficacy and Safety of Bilateral LUMEVOQ® Injections Confirmed

GenSight Biologics, a biopharmaceutical firm dedicated to advancing gene therapies for retinal and central nervous system disorders, has announced the 4-year efficacy and safety outcomes from the REFLECT Phase III clinical trial of LUMEVOQ® (GS010; lenadogene nolparvovec). The data reveals that the gene therapy's visual acuity benefits have been maintained over the long term, with a favorable safety profile.

The REFLECT trial, which included patients with Leber Hereditary Optic Neuropathy (LHON), demonstrated that LUMEVOQ®'s one-time administration resulted in sustained visual improvement. Notably, patients who received bilateral injections experienced an additional benefit over those who had unilateral treatment. The visual acuity of bilaterally treated patients remained superior to those with unilateral injections, a difference that has been consistent since the first year and a half post-treatment.

Dr. Patrick Yu-Wai-Man, a key opinion leader in ophthalmology and the International Principal Investigator of the REFLECT trial, emphasized the sustained benefits of lenadogene nolparvovec 4 years post-treatment. He highlighted that the safety profile for patients receiving bilateral injections was comparable to those treated unilaterally.

The data from the trial showed that the average visual acuity for all LUMEVOQ®-treated eyes improved by more than the +15 letter threshold, which is considered a clinically meaningful improvement. The placebo eyes also showed an improvement, indicating a consistent contralateral treatment effect observed across all clinical trials.

Laurence Rodriguez, CEO of GenSight Biologics, commented on the significance of the sustained effect on vision, stating that the long-lasting impact from a single administration sets gene therapy apart from other treatment options. This durability can enhance patient adherence and improve the quality of life.

Furthermore, 73% of patients who received bilateral injections experienced a clinically meaningful level of improvement. The likelihood of achieving on-chart vision was twice as high with bilateral treatment compared to unilateral treatment.

The safety profile of LUMEVOQ® was confirmed to be favorable, with no study discontinuations related to systemic or ocular adverse events and no serious ocular adverse events reported. The primary ocular adverse event was intraocular inflammation, which was mostly mild and treatable with conventional methods.

The REFLECT trial is a randomized, double-masked, placebo-controlled study involving 98 subjects with vision loss due to LHON caused by a mutated ND4 mitochondrial gene. The subjects received an intravitreal injection of lenadogene nolparvovec in their first affected eye, with the second affected eye randomized to receive either a second injection of LUMEVOQ® or a placebo. The patients will be followed up to 5 years post-injection to monitor the efficacy and safety of LUMEVOQ® over time.

LHON is a rare maternally inherited mitochondrial genetic disease that leads to severe and irreversible vision loss, primarily affecting adolescents and young adults. GenSight Biologics' LUMEVOQ® targets LHON by using a mitochondrial targeting sequence proprietary technology platform, aiming to restore the missing or deficient mitochondrial function.

The REFLECT trial's primary endpoint is the best-corrected visual acuity (BCVA) reported in LogMAR at 1.5 years post-treatment in the second-affected or not-yet-affected eye. Secondary efficacy endpoints include changes from baseline in BCVA, OCT, contrast sensitivity, and quality of life scales.

The trial was conducted across Europe/UK, the US, and Taiwan, with 98 subjects successfully screened and treated. Long-term follow-up is ongoing to further assess the safety and efficacy of LUMEVOQ®.