Ophthalmology Commons^™

Safety And Efficacy Of Ixoberogene Soroparvovec In Neovascular Age-Related Macular Degeneration In The United States (Optic): A Prospective, Two-Year, Multicentre Phase 1 Study, Arshad M. Khanani, David S. Boyer, Charles C. Wykoff, Carl D. Regillo, Brandon G. Busbee, Dante Pieramici, Carl J. Danzig, Brian C. Joondeph, James C. Major, Adam Turpcu, Szilárd Kiss

Wills Eye Hospital Papers

Background

Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD.

Methods

In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to …

Indirect Comparison Of Lenadogene Nolparvovec Gene Therapy Versus Natural History In Patients With Leber Hereditary Optic Neuropathy Carrying The M.11778g>A Mt-Nd4 Mutation, Valerio Carelli, Nancy J. Newman, Patrick Yu-Wai-Man, Valerie Biousse, Mark L. Moster, Prem S. Subramanian, Catherine Vignal-Clermont, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Gema Rebolleda Fernández, Bart K. Chwalisz, Rudrani Banik, Jean François Girmens, Chiara La Morgia, Adam A. Debusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, François Montestruc, Michel Roux, Magali Taiel, José-Alain Sahel

Wills Eye Hospital Papers

INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174.

METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 …

Narrative Review-Drug Delivery In Age-Related Macular Degeneration, Rachel Israilevich, Raziyeh Mahmoudzadeh, Mirataollah Salabati, David Xu

Wills Eye Hospital Papers

This narrative review highlights routes of ocular drug delivery for age-related macular degeneration (AMD). AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7% of blindness worldwide. Advanced AMD can be classified into two subtypes: late-stage dry AMD [known as geographic atrophy (GA)] and neovascular AMD (nAMD). GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium. Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium (RPE) or retina, a process known as choroidal neovascularization …

Assessing The Accuracy, Quality, And Readability Of Patient Accessible Online Resources Regarding Ocular Gene Therapy And Voretigene Neparvovec., Swetha Davuluri, Nicolas A. Yannuzzi, Amy Kloosterboer, Ajay E. Kuriyan, Jayanth Sridhar

Wills Eye Hospital Papers

Purpose: To evaluate the accuracy, quality, and readability of online information regarding the Food and Drug Administration (FDA) approved ocular gene therapy voretigene neparvovec (Luxturna, Spark Therapeutics, Philadelphia, PA, USA).

Methods: Ten online resources about voretigene neparvovec were assessed in this cross-sectional study. A novel 25-question assessment was created to evaluate the information most relevant to patients. Each article was assessed by independent graders using the assessment and the DISCERN instrument. An online readability tool, Readable, was used to assess readability. Accountability was evaluated using the Journal of the American Medical Association (JAMA) benchmarks.

Results: The average questionnaire score for …

Intravitreal Gene Therapy Vs. Natural History In Patients With Leber Hereditary Optic Neuropathy Carrying The M.11778g>A Nd4 Mutation: Systematic Review And Indirect Comparison, Nancy J. Newman, Patrick Yu-Wai-Man, Valerio Carelli, Valerie Biousse, Mark Moster, Catherine Vignal-Clermont, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Jean-François Girmens, Chiara La Morgia, Adam A. Debusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, François Montestruc, Michel Roux, Magali Taiel, José-Alain Sahel

Wills Eye Hospital Papers

Objective: This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies.

Design: A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2-ND4 vs. 11 pooled NH studies used as an external control.

Subjects: The LHON subjects carried the m.11778G>A ND4 mutation and were aged ≥15 years at onset of vision loss.

Methods: A total of 76 subjects received a single …

Patients And Animal Models Of Cngβ1-Deficient Retinitis Pigmentosa Support Gene Augmentation Approach., Simon M Petersen-Jones, Laurence M. Occelli, Paige A. Winkler, Winston Lee, Janet R Sparrow, Mai Tsukikawa, Sanford L. Boye, Vince Chiodo, Jenina E. Capasso, Elvir Becirovic, Christian Schön, Mathias W. Seeliger, Alex V. Levin, Stylianos Michalakis, William W. Hauswirth, Stephen H. Tsang

Wills Eye Hospital Papers

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation …