Lumevoq (lenadogene nolparvovec) / GenSight - LARVOL DELTA

Systematic review of Leber's hereditary optic neuropathy - Clinical diagnosis, genetics overview and current concepts of treatment. (PubMed, Indian J Ophthalmol) - "Idebenone, a synthetic CoQ10 analog, is the first pharmacologic agent approved in Europe, demonstrating partial visual recovery in patients treated early by improving mitochondrial electron transport and reducing oxidative stress. Gene therapy using allotopic expression of ND4 via adeno-associated viral vectors (rAAV2/2-ND4) has shown improvement in both eyes even after unilateral injection...High-throughput genetic testing, including whole-genome sequencing and clinical exome analysis, enables precise identification of nuclear modifiers that influence LHON phenotypes, facilitating early diagnosis and intervention. Current clinical trials, including RESTORE and REFLECT, emphasize the importance of prompt treatment to optimize visual outcomes."

Journal • Review • Gene Therapies • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Gene Therapy for Leber Hereditary Optic Neuropathy (LHON): A Systematic Review and Meta-Analysis. (PubMed, Neuroophthalmology) - "Adverse events were mostly mild ocular inflammation, with no treatment-related mortality. rAAV2/2-ND4 is a moderately effective and safe treatment for LHON, though long-term outcomes and predictors of response remain unclear."

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

Diffusion of AAV2-based gene therapy into contralateral optic nerve in Leber hereditary optic neuropathy (ARVO 2026) - "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 variant...The gradient of transgene quantification along the visual pathways in patient 2, as well as its detection in the entorhinal cortex, which is unrelated to the visual pathway, suggest alternative routes besides axonal and trans-synaptic, such as vascular and/or cerebrospinal fluid diffusion. This contralateral diffusion may partially explain the bilateral clinical effect of LN."

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

Efficacy of Lenadogene Nolparvovec Gene Therapy Versus Idebenone: A Matched Adjusted Indirect Comparison (AAN 2026) - "In a post-hoc sensitivity analysis comparing EAP to RESCUE (ESS: 33), CRR was 39.0% for idebenone vs 69.5% for LNGT (OR=3.59, [1.42; 9.06]; p=0.011). Conclusions 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

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. The safety of LNGT was comparable to those of the 189 patients from clinical trial studies, with no difference in the incidence of intraocular inflammation between patients treated bilaterally and unilaterally (51.2% vs 52.4%). Conclusions 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 in Leber hereditary optic neuropathy due to the m.11778G>A MT-ND4 variant: two matching adjusted indirect comparisons. (PubMed, Br J Ophthalmol) - "The two MAICs demonstrated a clinically meaningful higher visual recovery at 24 months with lenadogene nolparvovec than with idebenone in patients with LHON due to the m.11778G>A MT-ND4 variant."

Journal • 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