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

Khanani, Arshad M.; Boyer, David S.; Wykoff, Charles C.; Regillo, Carl D.; Busbee, Brandon G.; Pieramici, Dante; Danzig, Carl J.; Joondeph, Brian C.; Major, James C.; Turpcu, Adam; Kiss, Szilárd

doi:10.1016/j.eclinm.2023.102394

Cited by 16 publications

(5 citation statements)

References 28 publications

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“…The Phase I trial enrolled patients previously controlled with frequent anti-VEGF injections who received high or low doses of ADVM-022, which was renamed to ixoberogene soroparvovec (ixo-vec). The high-dose population showed a 98% decrease in the number of anti-VEFGA injections, while the low-dose group -an 80% reduction [60]. Ocular treatment-emergent adverse events (TEAEs) related to ixo-vec were mild to moderate and included anterior chamber cells and vitreal cells.…”

Section: Advm-022mentioning

confidence: 99%

New Generation of Gene Therapies as the Future of Wet AMD Treatment

Blasiak,

Pawlowska,

Ciupinska

et al. 2024

Preprint

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Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms: dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the idea of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the road to the clinic of “one and done” therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.

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Section: Advm-022mentioning

confidence: 99%

New Generation of Gene Therapies as the Future of Wet AMD Treatment

Blasiak,

Pawlowska,

Ciupinska

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The Phase I trial enrolled patients who were previously controlled with frequent anti-VEGF injections and who received high or low doses of ADVM-022, which was renamed as ixoberogene soroparvovec (ixo-vec). The high dose population showed a 98% decrease in the number of anti-VEFGA injections required, while the low dose group showed an 80% reduction [60]. Ocular treatment-emergent adverse events (TEAEs) related to ixo-vec were mild to moderate and included anterior chamber cells and vitreal cells.…”

Section: Rgx-314mentioning

confidence: 99%

A New Generation of Gene Therapies as the Future of Wet AMD Treatment

Blasiak,

Pawlowska,

Ciupińska

et al. 2024

IJMS

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Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms, dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the concept of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the progress to the clinic of “one and done” therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.

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“…Gene therapy offers an exciting potential to have a one-time administration typically utilising an adeno-associated virus (AAV) to deliver a long-term expression of an anti-VEGF-A protein to manage nAMD [ 105 ]. Gene therapies in clinical development include ixoberogene soroparvovec (Adverum Biotechnologies, USA) currently in phase 1/2 trials that utilizes a novel vector capsid, AAV2.7m8 to deliver a gene that codes for an aflibercept-like protein intravitreally, and ABBV-RGX-314 (Abbvie-Regenxbio, USA) an AAV8 vector currently in two phase 2/3 nAMD studies evaluating intraretinal delivery of genes that code for a ranibizumab-like antibody fragment against VEGF-A, and another phase 2 nAMD trial using suprachoroidal delivery of the same gene product [ 106 – 108 ]. Some earlier gene therapy candidates including rAAV.sFLT-1 (Avalanche, USA) and AAV2-sFLT01 (Sanofi Genzyme, USA) did not advance past early clinical evaluation and challenges still remain for those in development regarding the optimal target/mode of administration and potential safety concerns [ 105 , 109 ].…”

Section: Current Treatment Landscape For Namdmentioning

confidence: 99%

Vascular Endothelial Growth Factor C and D Signaling Pathways as Potential Targets for the Treatment of Neovascular Age-Related Macular Degeneration: A Narrative Review

Leitch,

Gerometta,

Eichenbaum

et al. 2024

Ophthalmol Ther

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The development of treatments targeting the vascular endothelial growth factor (VEGF) signaling pathways have traditionally been firstly investigated in oncology and then advanced into retinal disease indications. Members of the VEGF family of endogenous ligands and their respective receptors play a central role in vasculogenesis and angiogenesis during both development and physiological homeostasis. They can also play a pathogenic role in cancer and retinal diseases. Therapeutic approaches have mostly focused on targeting VEGF-A signaling; however, research has shown that VEGF-C and VEGF-D signaling pathways are also important to the disease pathogenesis of tumors and retinal diseases. This review highlights the important therapeutic advances and the remaining unmet need for improved therapies targeting additional mechanisms beyond VEGF-A. Additionally, it provides an overview of alternative VEGF-C and VEGF-D signaling involvement in both health and disease, highlighting their key contributions in the multifactorial pathophysiology of retinal disease including neovascular age-related macular degeneration (nAMD). Strategies for targeting VEGF-C/-D signaling pathways will also be reviewed, with an emphasis on agents currently being developed for the treatment of nAMD.

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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

Cited by 16 publications

References 28 publications

New Generation of Gene Therapies as the Future of Wet AMD Treatment

New Generation of Gene Therapies as the Future of Wet AMD Treatment

A New Generation of Gene Therapies as the Future of Wet AMD Treatment

Vascular Endothelial Growth Factor C and D Signaling Pathways as Potential Targets for the Treatment of Neovascular Age-Related Macular Degeneration: A Narrative Review

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