REFLECT Phase III clinical trial with Lumevoq shows efficacy and safety in Leber Hereditary Optic Neuropathy. - GenSight.

The results show sustained efficacy and favorable safety for bilateral intravitreal injection of the gene therapy with a statistically significant visual acuity improvement from baseline in both treated eyes, showing an additional benefit of a bilateral injection compared to a unilateral injection. The findings reinforce the results observed at 2 years post-treatment administration, which were reported in December 20211, and at 1.5 years post-treatment administration, which were reported in June 2021.

Designed under a Special Protocol Assessment with the US FDA, REFLECT is a randomized, double-masked, placebo-controlled Phase III trial involving 98 subjects with vision loss due to Leber Hereditary Optic Neuropathy (LHON) caused by a mutated ND4 mitochondrial gene; enrolled ND4 subjects had vision loss up to one year from onset. Vision typically deteriorates to a nadir and stabilises to a level below the threshold for legal blindness. The ND4 mitochondrial mutation is associated with the most severe clinical form of LHON, with poor overall visual outcomes. All subjects received an intravitreal injection (IVT) of lenadogene nolparvovec in their first affected eye. The second affected eye was randomized to either a second IVT of Lumevoq or a placebo IVT, which was administered on the same day or the following day. 48 subjects were randomized to Lumevoq bilateral treatment, and 50 to lenadogene nolparvovec unilateral treatment (first-affected eye treated with lenadogene nolparvovec, second-affected eye treated with placebo).

The favorable safety profile of lenadogene nolparvovec continued to be confirmed, with the safety profile of the drug being demonstrated as comparable in bilaterally and unilaterally treated subjects. There was no study discontinuation related to systemic or ocular adverse events, and there were no serious ocular adverse events. The main ocular adverse event was intraocular inflammation, which was mostly mild and responsive to conventional treatment. REFLECT patients will be followed up to 5 years post-injection to monitor the efficacy and safety of lenadogene nolparvovec over time.