Lumevoq gene therapy in leber hereditary optic neuropathy

Title : Lumevoq gene therapy in leber hereditary optic neuropathy

Abstract:

Leber Hereditary Optic Neuropathy (LHON) is a rare, maternally inherited mitochondrial genetic disorder characterized by sudden, painless vision loss. The disease has a significant unmet medical need and is primarily caused by three mitochondrial DNA point mutations: G3460A, G11778A, and T14484C, located in the ND1, ND4, and ND6 genes, respectively. Among them, the m.11778G>A mutation in the ND4 gene is the most common (accounting for 75% of cases) and is associated with the most severe clinical phenotype.

Lenadogene nolparvovec (Lumevoq®) is a gene therapy based on a recombinant adeno-associated viral vector (rAAV2/2) encoding the human wild-type ND4 protein. It is designed to address the root cause of LHON in patients harboring the m.11778G>A mutation by restoring ND4 protein expression, thereby improving mitochondrial Complex I function and protecting retinal ganglion cells.

Three multicenter Phase III clinical trials — RESCUE, REVERSE, and REFLECT — demonstrated sustained, bilateral improvement in best-corrected visual acuity (BCVA) after unilateral or bilateral intravitreal injection of lenadogene nolparvovec. Across these trials, 189 patients were treated, showing meaningful restoration of visual function.

Early access programs have been initiated in the United States and Europe, underscoring the therapy’s potential to meet a significant therapeutic gap in mitochondrial optic neuropathies.

Audience Take Away Notes:

• A clear understanding of LHON as a rare genetic disorder with unmet clinical needs
• An overview of the pathophysiological mechanism targeted by the therapy
• Insights into the clinical development and results of lenadogene nolparvovec gene therapy
• Knowledge of next regulatory steps and access pathways
• Key clinical and developmental learnings from Phase III trials

Biography:

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.