Mitochondrial gene therapy to restore lost vision

GenSight Biologics is developing LUMEVOQ (GS010), a therapy that causes ND4, a mitochondrial protein, to be expressed in the nucleus and shuttled to the mitochondria. This concept of moving mitochondrial DNA into the nucleus, where it is better protected, is a key approach for combating mitochondrial dysfunction, one of the hallmarks of aging. The company has taken LUMEVOQ into multiple Phase 3 clinical trials for the treatment of Leber Hereditary Optic Neuropathy (LHON), a disease that causes blindness.

This company has had some issues with clinical trials in the past, as each patient had a single treated eye to test the efficacy of GS010 and the other eye was left untreated to serve as the control group. The problem was that administering this therapy seemed to affect the untreated eye along with the treated eye, leading to a lack of difference between the experimental group and the control group – thus possibly making an effective therapy seem ineffective.

In December 2020, the Phase 3 REVERSE clinical trial was a success, representing the moment when mitochondrial gene therapy became a reality in humans. The researchers report that by week 96 of the study, 25 participants showed a significant improvement of best-corrected visual acuity (BCVA) in at least one eye compared to the baseline taken before treatment. 29 of the 37 participants showed an improvement of vision in both eyes. They discovered that eyes were about three times more likely to regain 20/200 vision or better following treatment.

In June 2021, Gensight reported key efficacy and safety results at 78 weeks post-treatment in the REFLECT Phase 3 clinical trial for LUMEVOQ. The results show better BCVA improvements from bilateral intravitreal injections of the gene therapy compared to a unilateral injection.

In September 2021, results from the long-term follow up of the RESCUE & REVERSE Phase 3 clinical trials were published, which showed continued improvement in BCVA between 2 to 3 years post treatment.

LUMEVOQ has received a Cohort Temporary Authorization for Use in France, and EU marketing authorization is expected in H1 2022.

The researchers are also interested in using the same approach to treat other mitochondrial diseases.

GenSight is also developing GS030, a gene therapy that allows retinal cells to detect the presence of light, which is currently in a Phase 1/2 dose-escalation study.

Website: https://www.gensight-biologics.com/