GenSight’s REFECT Trial Completes Phase 3 Enrollment Early in Pursuing Treatment for LHON to Restore Vision

GenSight’s REFECT Trial Completes Phase 3 Enrollment Early in Pursuing Treatment for LHON to Restore Vision

GenSight launched this clinical trial to assess the safety and efficacy of a gene therapy called GS010 used to improve functional and structural retina outcomes in patients with LHON (due to the G11778A ND4 mitochondrial mutation when vision loss occurs for up to one year). GenSight reported that they have completed Phase 3 enrollment, achieving an important milestone.

What is LHON?

LHON means “Leber hereditary optic neuropathy,” which is an inherited form of vision loss. Although this condition usually beings in a person’s teens or twenties, rare cases may surface in early childhood or later in childhood. Males are affected more often than females. Blurring and clouding of vision typically represents early symptoms of LHON. It is caused by a genetic mutation in the ND4mitochondrial gene.

The Study

Known as REFLECT, the multi-center, randomized, double-blind placebo-controlled trial is designed to evaluate the efficacy and safety of a single injection of GS010 into the eyes of the patients with LHON, which is caused by a genetic mutation in the ND4 mitochondrial gene.

Eligible patients who have reported vision loss up to one year have been recruited to participate in the study at research sites in the United States, Europe and Taiwan.

Study Status

Although GenSight had planned to have 90 patients enrolled before September, it has now reached 98 patients that have been enrolled and treated—meaning the study is ahead of schedule. Principal Investigator for REFLECT, Nancy Newman, MD, with Emory School of Medicine noted, “The recruitment of nearly 100 patients in less than two years is a tribute to the support of the LHON community in this partnership among researchers, clinicians and patients trying to bring therapy and hope to this blinding disease.”

Patients are randomly assigned to receive either one injection of GS010 into both eyes (treatment group) or one injection of GS010 into one eye and one injection of placebo into the other (placebo group).

Based on best corrected visual acuity (BCVA), the study team will assess endpoint from baseline until week 52 (one year after treatment) in the patient’s second affected or not-yet affected eye. BVCA changes from baseline until two years after treatment in their second affected or not-yet affected eye compared to placebo and their first affected eye treated with GS010, contract sensitivity, optical coherence tomography (a non-invasive imaging test that uses light to take pictures of the retina) and quality of life—represents secondary endpoints.

GenSight reported that the first patient received treatment in March 2018 and that topline data from the first year of the study should be available by the end of 2020, reports Joana Carvalho of Mitochondrial Disease News.

GenSight Accelerated Marketing Authorization Plans for Both United States and Europe

The REFECT study has received FDA “special protocol assessment” (SPA) status, meaning that the regulatory agency has agreed that the sponsor’s trial design, clinical endpoints and analyses are sufficient to support future marketing application submission for GS010 in the United States. In Europe, this isn’t necessary, reports Mitochondrial Disease News, as the European Medicines Agency (EMA) is factoring in two other Phase 3 trials including 1) RESCUE and 2) REVERSE as pivotal for filing the marketing authorization application (MAA) for GS010 in Europe.

GenSight Background

Founded in 2011 and based in Paris, France, the venture has raised $102 million including an IPO in 2016. They are dedicated to the development and commercialization of gene-therapy-based treatments of retinal degenerative diseases. Based on recent results obtained by the teams of its scientific founders, the company develops innovative approaches to prevent retinal degeneration in selected pathological conditions and to restore vision in patients suffering from very low vision or blindness.

What is GS010?

GS010 is an AAV2 gene therapy vector that encodes the human wild-type ND4 protein, which GenSight is developing as a treatment of LHON caused by mutation of the ND4 gene. The ND4 gene is normally located in the mitochondria where ND4 proteins are synthesized. GS010 allows efficient allotopic expression of the mitochondrial gene ND4 in the nucleus thanks to proprietary Mitochondrial Targeting Sequence that shuttles the messenger RNA from the nucleus directly to the outer membrane of the mitochondria. There, the ND4 proteins are synthesized and incorporated into the mitochondria. Wild-type ND4 proteins then integrate into Complex I of the respiratory chain and rescue the deficiency.

Lead Research/Investigator

Nancy Newman, MD, with Emory School of Medicine, Principal Investigator

Research Sites Produce Results

Clearly this study has exhibited success, given the sponsor has reported on the key milestone of 100% patient enrollment and treatment ahead of schedule. The LHON community came together on this one for results. Key research sites involved:

United States

Doheny Eye Center UCLA, Pasadena, CA, University of Colorado Health Eye Center, Aurora, CO; Massachusetts Eye and Ear Infirmary, Boston, MA; Icahn School of Medicine at Mount Sinai, New York, NY; Wills Eye Institute—Ocular Oncology Service, Philadelphia, PA; Vanderbilt Eye Institute, Nashville, TN


Universitair Ziekenhuis Gent, Gent Belgium; CHNO Les Quinze Vingts, Paris France; IRCCS Instituto delle Scienze Neurologiche di Bologna UOC Clinica Neurologica, Bologna, Italy; Hospital Universitario Ramon y Cajal, Madrid, Spain; Moorfields Eye Hospital, London, UK


Taipei Veterans General Hospital, Taipei, Taiwan