Lumevoq (lenadogene nolparvovec) / GenSight - LARVOL DELTA

Lenadogene Nolparvovec Gene Therapy for Leber Hereditary Optic Neuropathy in the Real-life Setting (AAN 2026) - "Most (84.1%) patients were treated with idebenone at or after LNGT injection. Injection of LNGT in the real-life setting was associated with a clinically meaningful improvement in visual acuity from nadir and a favorable safety profile."

Clinical • Gene therapy • Gene Therapies • Inflammation • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Efficacy of Lenadogene Nolparvovec Gene Therapy Versus Idebenone: A Matched Adjusted Indirect Comparison (AAN 2026) - "The two MAICs demonstrated a clinically meaningful higher visual recovery at 24 months with LNGT than with idebenone in ND4 patients."

Clinical • Gene therapy • Gene Therapies • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

REVISE: Efficacy and Safety Study of Bilateral IVT Injection of GS010 at Two Dose Levels in LHON Patients (clinicaltrials.gov) - P2 | N=14 | Recruiting | Sponsor: GenSight Biologics | Not yet recruiting ➔ Recruiting

Enrollment open • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

GS-LHON-CLIN-08: A dose-ranging randomized, open-label study evaluating the effect of bilateral intravitreal injection of GS010 at two dose levels on visual acuity and retinal mitochondrial activity in patients affected with ND4 Leber Hereditary Optic Neuropathy The REVISE Study (clinicaltrialsregister.eu) - P1/2 | N=14 | Recruiting | Sponsor: Gensight Biologics

New P1/2 trial • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

A Phase 3, Multicenter, Randomized, Double-Masked, Sham-Controlled Clinical Trial for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation (clinicaltrials.gov) - P3 | N=95 | Active, not recruiting | Sponsor: Wuhan Neurophth Biotechnology Limited Company

New P3 trial • Gene Therapies • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

REVISE: Efficacy and Safety Study of Bilateral IVT Injection of GS010 at Two Dose Levels in LHON Patients (clinicaltrials.gov) - P2 | N=14 | Not yet recruiting | Sponsor: GenSight Biologics

New P2 trial • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term outcomes of bilateral injection of lenadogene nolparvovec gene therapy for leber hereditary optic neuropathy (EVER 2025) - No abstract available

Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in patients with m.11778G>A MT-ND4 leber hereditary optic neuropathy (EVER 2025) - No abstract available

Clinical • Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Predictive factors of final visual outcome in patients with Leber hereditary optic neuropathy treated with lenadogene nolparvovec gene therapy (EVER 2025) - No abstract available

Biomarker • Clinical • Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in patients with m.11778G>A MT-ND4 leber hereditary optic neuropathy (EVER 2025) - No abstract available

Clinical • Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Lenadogene nolparvovec gene therapy for leber hereditary optic neuropathy in the real-life setting (EVER 2025) - No abstract available

Clinical • Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Lenadogene nolparvovec gene therapy for leber hereditary optic neuropathy in the real-life setting (EVER 2025) - No abstract available

Clinical • Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term outcomes of bilateral injection of lenadogene nolparvovec gene therapy for leber hereditary optic neuropathy (EVER 2025) - No abstract available

Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Efficacy and safety of intravitreal rAAV2-ND4 therapy for Leber's hereditary optic neuropathy. (PubMed, Eye (Lond)) - "This Phase 1/2 trial demonstrated no serious safety concerns among the 12 participants. And dose of 4.5 × 109 vg, 0.05 mL was to be used in future Phase 3 study."

Journal • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • Uveitis

Rasch analysis of the NEI-VFQ-25: vision-related quality of life in Leber hereditary optic neuropathy after lenadogene nolparvovec gene therapy. (PubMed, BMJ Open Ophthalmol) - "The scoring structure of the original NEI-VFQ-25 has limitations that undermine its psychometric validity as a measure of VRQoL. Using the Rasch-revised NEI-VFQ-25, we determined that improvement in VRQoL after treatment with lenadogene nolparvovec was driven predominantly by an improvement in socioemotional functioning."

Clinical • HEOR • Journal • Gene Therapies • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

REFLECT: Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year (clinicaltrials.gov) - P3 | N=98 | Completed | Sponsor: GenSight Biologics | Active, not recruiting ➔ Completed

Trial completion • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Infographic: landmark trials in neuro-ophthalmology - results of the REVERSE trial for unilateral gene therapy rAAV2/2-ND4 in leber hereditary optic neuropathy. (PubMed, Eye (Lond)) - No abstract available

Journal • Gene Therapies • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Predictors of Final Visual Outcome in Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy. (PubMed, Invest Ophthalmol Vis Sci) - "A better baseline BCVA in the dynamic phase of the disease was associated with a better final BCVA (-0.09 logMAR; 95% CI, -0.11 to -0.08; P < 0.0001). Better baseline BCVA values and baseline thicker GCL and RNFL at OCT measurements are key predictive factors of the improved BCVA 1.5 years after treatment in patients with MT-ND4 LHON who received lenadogene nolparvovec at least 6 months after disease onset."

Journal • Gene Therapies • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Efficacy and safety of lenadogene nolparvovec Gene therapy for leber hereditary optic neuropathy in the real-life setting (SOE 2025) - "Preliminary analyses show that injection of LNGT in the real-life setting was associated with a clinically meaningful improvement in visual acuity from nadir and a favorable safety profile similar to that observed in the clinical studies."

Clinical • Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Latest data from lenadogene nolparvovec gene therapy trials for Leber hereditary optic neuropathy (SOE 2025) - "Over 10 years, 252 MT-ND4 LHON patients have received LNGT, with good safety profile and improved BCVA and quality-of-life."

Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

New insights on AAV2-ND4 transfer between eyes: ocular post-mortem analyses in Leber hereditary optic neuropathy following AAV2 gene therapy (SOE 2025) - "Purpose: Lenadogene nolparvovec (LN) is an AAV2-based gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A MT-ND4 mutation... This is the first postmortem study of human eyes injected with AAV2-based gene therapy. AAV2-ND4 transfected various retinal cells and the axons of ON of both eyes despite only unilateral administration. Remarkably, diffusion of AAV2-ND4 seems to lead to concentrations in the nasal and inferior quadrants of the ON cross-sectional profiles."

Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

A viewpoint about Lenadogene nolparvovec failing to meet its primary endpoint even though it permanently corrects the m.11778G>A mutation causative of LHON. (PubMed, Eye (Lond)) - No abstract available

Journal

Idebenone vs. rAAV2-ND4 gene therapy in the treatment of Leber's hereditary optic neuropathy: An indirect comparison meta-analysis. (PubMed, Indian J Ophthalmol) - "rAAV2-ND4 provides better visual acuity results at 6 months, and idebenone provides better visual acuity results at 1 year. Further studies are recommended to formulate a complete idea about the long-term results (>2 years)."

Clinical • Journal • Retrospective data • Review • Gene Therapies • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

GenSight Biologics Reports Cash Position as of March 31, 2025, and Provides Business Update (Businesswire) - "GenSight Biologics’ cash and cash equivalents totaled €0.9 million as of March 31, 2025...With the equity-with-warrants-attached financing announced in March 2025 (approximately €0.9 million) and the anticipated collection of approximately €1.1 million in Research Tax Credit (CIR) in April, and based on current operations, plans, and assumptions, this balance should fund operations until early June 2025...fundraising activities are underway to extend the cash runway and to initiate the RECOVER Phase III clinical trial and UK MHRA marketing application for LUMEVOQ...In parallel, the Company is continuing preparations to refine the RECOVER study design to incorporate feedback from the FDA and the EMA....It has adjusted its fundraising and other activities to minimize any risk to the timely initiation of the trial, which is targeted for H1 2026."

Commercial • New P3 trial • Ophthalmology

Predictive Factors of Final Visual Outcome in Patients with Leber Hereditary Optic Neuropathy Treated with Lenadogene Nolparvovec Gene Therapy (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Biomarker • Clinical • Gene therapy • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis