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

eClinicalMedicine · 11 authors, 12 centres

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TL;DR

The primary outcome was safety; secondary outcomes included vision and treatment burden.

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The primary outcome was safety; secondary outcomes included vision and treatment burden. The most common adverse events were ocular inflammation (anterior chamber and vitreal cells), which were dose-dependent and responsive to topical steroids. No systemic ixo-vec-related adverse events were reported. A key finding was a reduction in mean annualized anti-VEGF injections by 80% in the low-dose group and 98% in the high-dose group. The results suggest ixo-vec has potential as a durable therapy to reduce treatment burden in nAMD.

STUDY TYPE

RCT

SPECIALTY

ophthalmology

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AI pipeline

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ORIGINAL PAPER

PMC10751837

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

eClinicalMedicine

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ABSTRACT

Summary 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 anti-VEGF were assigned to four cohorts differing by ixo-vec dose (2 × 10 11 vs 6 × 10 11 vector genomes (vg/eye)) and prophylactic steroids (oral prednisone vs topical difluprednate). The primary outcome was the type, severity, and incidence of ocular and systemic adverse events (AEs); secondary endpoints included vision, central subfield thickness (CST), and the number of supplemental injections. This study was registered with ClinicalTrials.gov , NCT03748784 . Findings Thirty patients with nAMD were enrolled between November 14, 2018 and June 30, 2020 at nine study sites in the United States. No systemic ixo-vec related AEs were noted. Across both dose groups the most common adverse event was anterior chamber cell, which was reported in 11 participants in the 6 × 10 11 dose group and in 7 participants in the 2 × 10 11 dose group; intraocular inflammation was responsive to topical corticosteroids, with no anterior chamber cells or vitreous cells observed in 2 × 10 11 vg/eye patients at the end of the study. Vision and CST remained stable throughout two years with annualised anti-VEGF injections reduced by 80% (10.0 mean annualised anti-VEGF injections to 1.9) in 2 × 10 11 vg/eye and 98% (9.8 mean annualised anti-VEGF injections to 0.2) in 6 × 10 11 vg/eye cohorts. Interpretation Ixo-vec was generally well-tolerated, maintained vision, and improved anatomical outcomes in nAMD, with a substantial reduction in anti-VEGF injections. A single administration of an in-office gene therapy, with vectorised protein with an already established clinical benefit, has the potential to revolutionise the management of common ocular disorders requiring ongoing, frequent therapeutic interventions. Funding Adverum Biotechnologies.

CITATION EXPORT

Arshad M. Khanani, David S. Boyer, Charles C. Wykoff et al.. 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. eClinicalMedicine. (2024). https://doi.org/10.1016/j.eclinm.2023.102394

AUTHORS

11 · 12 CENTRES

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

aSierra Eye Associates, Reno, NV, USA
bThe University of Nevada, Reno School of Medicine, Reno, NV, USA
cRetina Vitreous Associates Medical Group, Beverly Hills, CA, USA
dRetina Consultants of Texas, Retina Consultants of America, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA
eMid Atlantic Retina, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA
fTennessee Retina, Nashville, TN, USA
gCalifornia Retina Consultants, Bakersfield, CA, USA
hRand Eye Institute, Deerfield Beach, FL, USA
iFlorida Atlantic University, Charles E. Schmidt School of Medicine, Boca Raton, FL, USA
jColorado Retina Associates, Denver, CO, USA
kAdverum Biotechnologies, Redwood City, CA, USA
lDepartment of Ophthalmology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA