Lumevoq (GS010)

Lumevoq (GS010) is a gene therapy being developed by GenSight Biologics for the treatment of Leber hereditary optic neuropathy (LHON), a rare type of mitochondrial disease that causes blindness and disability in teens and young adults.

Lumevoq was granted a temporary authorization for use  in December 2019 by the French National Drug Safety Agency to treat a patient affected by LHON in a Paris hospital.

How does Lumevoq work?

LHON is caused by mutations in the mitochondrial genes ND1ND4, or ND6, which provide instructions to make proteins responsible for the production of energy in the mitochondria. About 60% of LHON cases are caused by the so-called G11778A mutation in the ND4 gene. These gene mutations lead to dysfunction in retinal ganglion cells in the retina, resulting in vision loss.

Lumevoq uses a harmless virus called adeno-associated virus 2 (AAV2) to introduce a healthy copy of the ND4 gene into the nucleus of a cell. Since the product of the ND4 gene is a mitochondrial protein, the messenger RNA (mRNA) of the healthy ND4 gene introduced by the AAV2 virus has to be shuttled from the cell nucleus to the mitochondrial membrane. This is achieved using a proprietary mitochondrial targeting sequence. The ND4 mRNA that has been shuttled to the mitochondria can then be used to produce healthy ND4 protein that can take part in energy production, thereby restoring visual acuity.

Lumevoq in clinical trials

The safety, tolerability, and effectiveness of Lumevoq are being evaluated in several clinical trials.

A Phase 1/2 trial (NCT02064569) is evaluating the safety of the treatment in 19 patients with LHON. The preliminary data from the trial, announced by GenSight in a press release, revealed that patients treated with a single injection of Lumevoq showed long-term sustained improvement in visual acuity when examined 2.5 years after treatment. The study is expected to be completed in June 2020.

The effectiveness of Lumevoq is being evaluated in two Phase 3 clinical trials, RESCUE (NCT02652767) and REVERSE (NCT02652780) in patients with a mutation in the ND4 gene.

The main goal of the RESCUE study is to assess the effectiveness of Lumevoq in improving vision in patients who experience vision loss up to six months after the onset of LHON. The REVERSE study is looking at the effectiveness of the treatment in patients who have experienced vision loss from seven months to up to one year after the onset of LHON. REVERSE was completed in December 2018. RESCUE is ongoing but no longer recruiting participants.

Results from week 96 of the REVERSE trial indicated that Lumevoq showed a favorable safety profile and continued to be effective two years after injection with clinically meaningful improvements in best-corrected visual acuity (BCVA), which is a measure of the best distance vision with glasses or contact lenses. A BCVA of 20/20 is considered normal vision, while 20/200 or worse is considered legally blind in the U.S. Similar results were obtained at 96 weeks in the RESCUE trial, with Lumevoq-treated patients recovering more than two-thirds of their initial vision loss.

Two other clinical trials, REFLECT (NCT03293524) and REALITY (NCT03295071), are also underway.

The main objective of the Phase 3 REFLECT study is to evaluate the safety and effectiveness of Lumevoq in treating vision loss for up to one year after the onset of LHON in patients ages 15 and older. The enrollment of the 90 participants in the study was completed ahead of schedule. The study is expected to be completed by June 2021, with top-line, week 52 results expected towards the end of 2020. 

REALITY is a registry study to understand the natural history of visual, functional, and structural changes and other associated symptoms in patients with LHON. REALITY is recruiting an estimated 50 participants across Spain, Italy, France, the U.K., and the U.S. Participants will be followed over a period of three years.

Preliminary analysis of REALITY data revealed an irreversible loss of visual acuity in 15 people, all of whom were at least 15 years old at the time of LHON onset. This pattern was consistent when compared with pooled baseline data from the REVERSE and RESCUE trials.

A long-term follow-up study (NCT03406104) for patients treated in the RESCUE or REVERSE trials is recruiting an estimated 74 participants. The study will assess the safety and efficacy of Lumevoq for up to five years post-treatment. The study is expected to be completed in August 2022.

Other information

Initial top-line data from weeks 48 and 72 of the REVERSE trial indicated an unexpected bilateral improvement in the BCVA of the untreated eye in a manner similar to the Lumevoq-treated eye. This led to the trial’s failing its primary objective, as there was no appreciable difference between the control and treated eyes. It also led to speculation that gene therapy in one eye may affect the other eye as well. The improvements in visual acuity in control eyes were seen even at week 96, but they were not statistically significant from that of Lumevoq-treated eyes.


Last updated: Jan. 8, 2020


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