• Bilateral treatment effect following unilateral injection of gene therapy for ND4-LHON was independently reported by three research groups
  • LUMEVOQ® is the first gene therapy treating a mitochondrial disease for which marketing approval has been requested from the European Medicines Agency

Paris, France, October 6, 2021, 7:30 am CET – GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that the peer-reviewed journal International Ophthalmology Clinics has published a review of current and past gene therapy clinical trials for the treatment of Leber hereditary optic neuropathy (LHON).

The paper*, published in the October issue of the International Ophthalmology Clinics under the title “Gene Therapies for the Treatment of Leber Hereditary Optic Neuropathy”, discusses the trials and the outcomes available to date.

Three research groups have developed gene therapies for ND4-LHON, the most prevalent and severe genotype of LHONa,b: GenSight Biologics (one Phase I/II trial and three Phase III trials)c,d,e, the Huazhong University of Science and Technology (one Phase I and one open-label trial) and the Bascom Palmer Eye Institute of the University of Miami (one Phase I/II trial). Only GenSight’s gene therapy, LUMEVOQ®, has completed Phase III trials and reached the registration phase.

“The active research on gene therapies to treat LHON answers the acute need for a safe and effective treatment for patients confronting this blinding disease,” said Magali Taiel, MD, Chief Medical Officer of GenSight Biologics. “We at GenSight Biologics are excited to be at the forefront of these efforts, particularly in Europe where we are already in the registration phase, aiming to bring a therapeutic solution to these patients in 2022.”

Across these clinical trials and different clinical development programs, a sustained and clinically meaningful bilateral benefit was reported in a substantial proportion of ND4 patients who were unilaterally treated, at rates that surpass the expected natural history of the disease.

“This invited review provides a global perspective on the current gene-based approaches developed to tackle this devastating disease and discusses the positive outcomes observed with LUMEVOQ during the recent trials, bringing hope to our patients”, commented lead author José-Alain Sahel, MD,  Distinguished Professor and Chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and UPMC (University of Pittsburgh Medical Center), USA; Co-founder of GenSight Biologics; and Founder of the Institut de la Vision (Sorbonne-Université/Inserm/CNRS), Paris, France, which developed and patented the Mitochondrial Targeted Sequence (MTS) technology used in LUMEVOQ®.

Safety data from all the trials so far indicate that intravitreal injection constitutes a safe and easy route of administration, avoiding the complications of sub-retinal surgery. All gene therapies investigated provide excellent systemic tolerability and mostly mild ocular side effects, responsive to conventional ophthalmologic treatments.

LUMEVOQ® is the first gene therapy treating a mitochondrial disease for which marketing approval has been requested from the European Medicines Agency; the application was submitted in September 2020.

The paper is available at https://pubmed.ncbi.nlm.nih.gov/34584057/.


*About the paper:

 Gene Therapies for the Treatment of Leber Hereditary Optic Neuropathy

 Authors: José-Alain Sahel,1,2,3,4 Nancy J Newman,5 Patrick Yu-Wai-Man,6,7,8,9 Catherine Vignal Clermont,10,11 Valerio Carelli,12,13 Valérie Biousse,5 Mark L Moster,14 Robert Sergott,14 Thomas Klopstock,15,16,17 Alfredo A. Sadun,18 Laure Blouin,19 Barrett Katz,20 Magali Taiel.19


1 Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

2 Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France

3 Fondation Ophtalmologique A. de Rothschild, Paris, France

4 CHNO des Quinze-Vingts, Institut Hospitalo-Universitaire FOReSIGHT, INSERM-DGOS CIC 1423, Paris, France

5 Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA

6 Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

7 Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK

8 Moorfields Eye Hospital, London, UK

9 UCL Institute of Ophthalmology, University College London, London, UK

10 Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France

11 Centre Hospitalier National d’Ophtalmologie des Quinze Vingts, Paris, France

12 IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica , Bologna, Italy

13 Unit of Neurology, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy

14 Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA

15 Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University Munich, Germany

16 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany

17 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

18 Doheny Eye Institute / UCLA School of Medicine, Los Angeles, CA, USA

19 GenSight Biologics, Paris, France

20 Consultant for GenSight Biologics



a. Newman NJ, Carelli V, Taiel M, Yu-Wai-Man P. Visual Outcomes in Leber Hereditary Optic Neuropathy Patients With the m.11778G>A (MTND4) Mitochondrial DNA Mutation. J Neuroophthalmol. 2020 Dec;40(4):547-557.

b. Yu-Wai-Man P, Newman NJ, Carelli V, et al. LHON REALITY Study Group. Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study. Eye (Lond). 2021 Apr 28. Epub ahead of print.

c. Vignal-Clermont C, Girmens JF, Audo I, Said SM, Errera MH, Plaine L, O’Shaughnessy D, Taiel M, Sahel JA. Safety of Intravitreal Gene Therapy for Treatment of Subjects with Leber Hereditary Optic Neuropathy due to Mutations in the Mitochondrial ND4 Gene: The REVEAL Study. BioDrugs. 2021 Mar;35(2):201-214.

d. Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Sadun AA, Klopstock T, Vignal-Clermont C, Sergott RC, Rudolph G, La Morgia C, Karanjia R, Taiel M, Blouin L, Burguière P, Smits G, Chevalier C, Masonson H, Salermo Y, Katz B, Picaud S, Calkins DJ, Sahel JA. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Sci Transl Med. 2020 Dec 9;12(573):eaaz7423.

e. Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Barboni P, DeBusk AA, Girmens JF, Rudolph G, Karanjia R, Taiel M, Blouin L, Smits G, Katz B, Sahel JA; LHON Study Group. Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset. Ophthalmology. 2021 May;128(5):649-660.


About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics’ pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics’ lead product candidate, LUMEVOQ® (GS010; lenadogene nolparvovec), has been submitted for marketing approval in Europe for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. Using its gene therapy-based approach, GenSight Biologics’ product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery.

About Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of patients have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. The estimated incidence of LHON is approximately 800-1,200 new patients who lose their sight every year in the United States and the European Union.

About LUMEVOQ® (GS010; lenadogene nolparvovec)

LUMEVOQ® (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. “LUMEVOQ” was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018.