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Ixoberogene soroparvovec (Ixo-vec) intravitreal gene therapy for neovascular age-related macular degeneration (nAMD): Long-term results from the OPTIC
Quan Dong Nguyen, MD, MSc
Presenter:
Quan Dong Nguyen, MD, MSc1*; Brian C. Joondeph, MD2; James C. Major Jr, MD, PhD.3; Charles C. Wykoff, M.D., PhD4; David S. Boyer, MD5; Carl D. Regillo, MD, FACS6; Carl J. Danzig, MD7; Brandon G. Busbee, MD8; Dante Pieramici, MD9; Arshad M. Khanani, MD, MA10; Pauravi J. Gandhi, PhD11; Dina Akasheh, PhD, MBA11; Joanna Do11; Jennifer Danesh, MD11; Traci Clemons11; Lixin Wang, MD11; Adam Turpcu, PhD11; Rabia G. Ozden, MD11; Star Seyedkazemi, PharmD11
Authors:
Affiliation:
1. Byers Eye Institute at Stanford, Palo Alto, CA, USA
2. Colorado Retina Associates, Lakewood, CO, USA
3. Retina Consultants of Texas, Clinical Assistant Professor Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA
4. Retina Consultants of Texas, Professor of Clinical Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA
5. Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA
6. Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA
7. The Advanced Retina Institute, Bonita Springs, FL, USA
8. Tennessee Retina, Nashville, TN
9. California Retina Consultants, Santa Barbara, CA, USA
10. Sierra Eye Associates, Reno, NV, USA
11. Adverum Biotechnologies, Redwood City, CA, USA
Intravitreal (IVT) injections of vascular endothelial growth factor antagonists (anti-VEGF) stabilize vision in most treatment-compliant nAMD patients. However, the requirement for frequent injections often leads to poor compliance and suboptimal visual outcomes. In addition, fluctuations in retinal thickness caused by oscillating peak–trough anti-VEGF concentrations are associated with an increased risk of fibrosis and macular atrophy. Ixoberogene soroparvovec (ixo-vec) is an IVT gene therapy comprising an evolved AAV vector (AAV.7m8) and a transgene sequence encoding aflibercept, a clinically validated recombinant anti-VEGF protein.
The OPTIC trial (NCT04645212) is a Phase 1 study evaluating Ixo-vec in adults with nAMD who required frequent anti-VEGF injections. Eligible participants received a single IVT injection of Ixo-vec 6×1011(6E11) or 2×1011 (2E11) vg/eye with steroid prophylaxis. We herein report 4-year outcomes in the 2E11 vg/eye group, including safety, best corrected visual acuity (BCVA), central subfield thickness (CST), supplemental anti-VEGF injections, and aqueous aflibercept concentrations.
A total of 30 participants were enrolled; of these, 15 received Ixo-vec 2E11 vg/eye. Mean ±SD BCVA at baseline was 65.4 ±7.4 ETDRS letters and mean CST was 407.1 ±172.5 mm. Participants had received a mean of 9.9 ±1.3 annualized anti-VEGF injections in the prior 12 months, reflecting a high-need population. Assessment of outcomes at 4 years showed an 86% cumulative reduction in the mean annualized injection burden, with 47% of participants remaining injection free through 4 years. The mean changes in BCVA and CST were –2.9 letters and –117.7 µm, respectively. Aqueous aflibercept concentrations were sustained through up to 5 years. Ixo-vec was well tolerated. All participants were inflammation free (<1+ anterior chamber/vitreous cells) at one year and, with the exception of one participant with inflammation at the first scheduled assessment following cataract surgery (2.5 years), all remained inflammation free at 4 years.
Long-term outcomes in the OPTIC trial demonstrated that a single IVT injection of Ixo-vec was well tolerated and resulted in sustained intraocular aflibercept concentrations, preserved visual acuity, and a marked reduction in injection burden in a high-need nAMD population.