GenSight Biologics S.A. announced topline results on the safety and efficacy for its 3-year follow-up to the REFLECT phase 3 trial assessing the use of lenadogene nolparvovec (Lumevoq) as bilateral intravitreal injections for Leber Hereditary Optic Neuropathy (LHON).
Talk about LHON.
Leber Hereditary Optic Neuropathy (LHON) is a mitochondrial disease caused by genetic mutations to ND1, ND4, ND6—the most common being ND4 found within the mitochondrial DNA—that is primarily limited to retinal ganglion cells (RGCs). Extensive cell damage can occur due to the presence of ND4, resulting in a rapid loss of vision in both eyes.
Tell me more about Lumevoq.
Previously referred to as GS010, Lumevoq is a adenosine-associated virus (AAV) vector consisting of ND4. Lumoveq is delivered by intravitreal injection into retinal cells to mitigate the cellular damage whereby it can be replaced and restored, thus potentially leading to vision improvement.
How about the REFLECT trial?
The randomized, double-masked, placebo-controlled phase 3 trial (NCT03293524) was designed under a special protocol assessment through the FDA. A total of 98 participants were enrolled, all with vision loss due to LHON up to 1 year from onset.
Each participant received an intravitreal injection of Lumevoq into one affected eye; the second affected eye was randomized to receive either a second injection of Lumevoq (n = 48) or a placebo (n = 50) on the same day as the first or the day after.
What did previous data find?
Data from 1.5 years post-treatment reported a statistically significant improvement in mean best-corrected visual acuity (BCVA) for the bilateral Lumevoq-treated eyes compared to baseline (+12 ETRS letters in the first eye; +8 ETDRS letters in the second eye), whereas the unilateral (placebo-treated) eyes showed no statistically significant improvement (+8 ETDRS letters in first eye; +4 ETDRS letters in second eye).
Two-year post-treatment data also showed a statistically significant improvement in VA for bilateral Lumevoq-treated eyes, with 73% of participants experiencing at least +15 ETDRS letters.
Now tell me about this new data.
The latest three-year, post-treatment data found continued sustained efficacy and statistically significant VA improvements. Bilaterally-treated patients showed +17 to +10 ETDRS letters improvement compared to placebo.
Further, the dose effect noted at Year 1.5 and Year 2 was confirmed, with an absolute difference for the mean VA between arms of +6,5 ETDRS letters in favor of bilaterally-treated patients at Year 3.
What else?
According to GenSight, 62% of patients who were unable to read any letters on a screen at baseline (off-chart values for both eyes) are now able to read letters.
Any adverse events?
The main ocular adverse event (AE) was mild intraocular inflammation; however, there were no serious AEs reported as well as no study discontinuation related to any systemic or ocular AEs.
What’s next?
Study participants will continue to be monitored for a follow-up of 5-year post-injection assessment.