HYBRID EVENT: You can participate in person at Rome, Italy or Virtually from your home or work.

2nd International Conference on Orphan Drugs and Rare Diseases

March 17-19, 2025

March 17 -19, 2025 | Rome, Italy
Orphan Drugs 2023

Lumevoq gene therapy in leber hereditary optic neuropathy

Speaker at Orphan Drugs and Rare Diseases 2023 - Magali Taiel
GenSight Biologics, France
Title : Lumevoq gene therapy in leber hereditary optic neuropathy


Leber hereditary optic neuropathy (LHON) is a rare, maternally inherited mitochondrial genetic disease with a continued high unmet medical need. Three primary point mutations in the mtDNA are responsible for LHON in approximately 90% of subjects: G3460A, G11778A and T14484C, located respectively in the ND1, ND4 and ND6 genes. The m.11778G>A ND4 mutation is known to cause the most severe clinical form of LHON,  and is also the most frequent mutation, as it accounts for about 75% of LHON in North America and Europe. Lenadogene nolparvovec (Lumevoq) is a recombinant adeno-associated viral vector, serotype 2 (rAAV2/2), containing a cDNA coding the human wild-type mitochondrial NADH dehydrogenase 4 protein (ND4), which has been specifically developed to treat MT-ND4 LHON subjects, and is targeting the root cause of the disease. Restoring the expression of the ND4 protein could correct the deficiency due to the m.11778G>A ND4 mutation, leading to the improved activity and assembly of Complex I of the mitochondrial respiratory chain, helping to protect RGCs, eventually halting and reversing the disease. The three Phase-3 multi-center clinical trials RESCUE, REVERSE and REFLECT showed sustained bilateral improvement of best-corrected visual acuity (BCVA) following unilateral or bilateral intravitreal injection of lenadogene nolparvovec (rAAV2/2-ND4) gene therapy for the treatment of Leber Hereditary Optic Neuropathy (LHON) caused by the m.11778G>A mitochondrial DNA mutation in the MT-ND4 gene. Overall, 189 MT-ND4 patients were treated with lenadogene nolparvovec in clinical trials. Early expanded access programs have been granted in the US and Europe. Lenadogene nolparvovec brings a novel and efficacious treatment option, fulfilling an ongoing unmet medical need whilst restoring visual function in MT-ND4 LHON patients.

Audience Take Away Notes:

  • LHON, a rare disease, with unmet medical need
  • Insights on clinical development of lenadogene nolparvovec to treat MT-ND4 LHON patients
  • US and Europe regulatory pathways
  • Next steps for lenadogene nolparvovec registration
  • Key learnings



Dr. Taiel completed her doctorate in Medicine with board certified in Ophthalmology from Lariboisiere Saint Louis University, Paris, France, in 1993, and her Associate Professor degree in 1998. Dr Taiel completed her internship at academic Paris hospitals, was an Associate Professor of Ophthalmology, served as an Ophthalmology Department Head, and ran Surgical and Medical Ophthalmology private practice. After 13 years of Ophthalmology public and private practice, Dr Taiel has been engaged in the Pharma Industry for 20 years; she brings extensive experience and expertise in drug clinical development, gene therapy, and medical affairs. She started her carrier at Servier company headquarter, and then worked in Ophthalmology area at Pfizer for several years; she then held international and management positions in various therapeutic areas, including both technical and supervision duties, at Eli Lilly Company for many years. Then, as VP Clinical Development, she led Clinical Development and Operations, to develop antisense oligonucleotides in Inherited Retinal diseases at ProQR Therapeutics. She then moved to GenSight-Biologics in 2018, to supervise the Medical Department and lead Gene Therapy programs in Inherited Retinal and Neuro-Ophthalmology diseases, as the CMO of the company. Dr. Taiel has authored numerous protocols and articles published in peer reviewed journals, and made critical contributions to successful clinical development and launch of many products. She brings extensive years of experience from both academic medicine and pharma industry.