Age-related macular degeneration (AMD), a chronic eye disease characterized by visual distortion and loss of central vision, is the leading global cause of vision loss among older adults. Over 20 million people in the US have AMD. The prevalence increases with age, affecting more than 35% of adults over 80 years. Around 10–15% of patients progress to wet AMD (wAMD), which is also known as neovascular AMD. This is characterized by vascular endothelial growth factor (VEGF)-mediated growth and infiltration of abnormal blood vessels in the retina, and accounts for roughly 90% of severe vision loss. Without treatment, most eyes will lose central vision within 12 months or less.
Current treatments, involving injections of anti-VEGF drugs directly into the eye every 4–16 weeks, have revolutionized the management of wAMD by reducing the levels of fluid in the back of the eye. However, the levels can rise again between injections, which is known as the trampoline effect. This can mean that visual acuity waxes and wanes, even with full compliance, and patients are at risk of fibrosis and atrophy. Undertreatment may also result in declines in vision caused by disease progression.
“In the US, the current standard of care leads to suboptimal outcomes and high healthcare utilization, with 12% of Medicare Part B annually spent on anti-VEGF alone. Around 40% of patients will stop treatment in the first two years and 57% in five years, mostly because of the high treatment burden,” said Laurent Fischer, Adverum’s president and CEO.
Gene therapy offers a potential paradigm shift: a one-time, durable treatment delivering continuous intraocular anti-VEGF. California-based Adverum, based in Redwood City, is developing Ixoberogene soroparvovec (Ixo-vec)—formerly referred to as ADVM-022—as a gene therapy to deliver aflibercept, a clinically validated anti-VEGF biotherapeutic that has already been used in more than 89 million administrations and over 13 million patient-years of use worldwide. Its proprietary ‘One And Done’ approach could offer lifelong freedom from injections for wAMD.
Ocular gene therapy for wAMD
Gene therapy is well-suited for use in the eye, according to Lejla Vajzovic, vitreoretinal surgeon and professor of ophthalmology at Duke University School of Medicine in Durham, North Carolina. “The eye is a small, self-contained organ. Ocular gene therapy provides targeted treatment with little systemic exposure, and results that can be observed directly using imaging,” she stated.
Ixo-vec’s viral vector dose is 1,000 to 10,000-fold lower than the massive doses used in systemic gene therapies. While systemic gene therapies typically aim to replace, silence or edit genes, Ixo-vec delivers genetic instructions to produce a therapeutic protein without altering the genome.
One-time gene therapies for wAMD may offer benefits for both patients and physicians, explained Vajzovic. “While we have effective treatments for wAMD, they require frequent administration, and many patients discontinue therapy due to treatment burden, illness, caregiving responsibilities, or travel challenges. Reducing treatment frequency could also ease the strain on healthcare systems and allow clinicians to focus on other patient needs,” she said.
In a 2025 survey of nearly 1,000 retina specialists, almost half saw gene therapy as the most exciting upcoming treatment, more than the next three categories combined. This aligns with retina specialists’ view that longer-duration therapies remain the largest unmet need in wAMD.
Single-dose interventions
A one-time treatment like Ixo-vec enables a lower-cost, scalable model, which could also be an attractive option for countries with limited healthcare access.
Ixo-vec uses an adeno-associated viral capsid designed for retinal delivery that carries an optimized aflibercept coding sequence. Delivered as a single, in-office intravitreal injection, it enables retina cells to become biofactories that continuously produce aflibercept (Fig. 1).
Fig. 1 | Ixo-vec: Intravitreal gene therapy. An adeno-associated viral capsid delivers an optimized aflibercept coding sequence via an intravitreal injection, enabling transduced retina cells to produce aflibercept continuously. CNV, choroidal neovascularization; ILE, inner limiting membrane; RPE, retinal pigment epithelium.
“Ixo-vec is designed to maximize injection freedom for potential life-long benefit, meaning a potential functional cure for wAMD, and continued anti-VEGF protection for undertreated patients at risk of being lost to follow-up. Its one-time-treatment model may also create cost-effective outcomes for healthcare systems,” said Fischer.
By eliminating the fluid fluctuations associated with undertreatment or intermittent anti-VEGF dosing, Ixo-vec may also offer disease-modifying potential. In the phase 1 OPTIC trial, a multicenter, open-label, dose-ranging study, and the phase 2 LUNA trial, a multicenter, double-masked, randomized, parallel-group study, a single injection of Ixo-vec with a tapered regimen of topical steroid prophylaxis demonstrated durable intraocular expression of aflibercept beyond five years, vision preservation with consistent anatomical and functional stabilization, and >80% reduction in anti-VEGF treatment burden, as well as a favorable safety profile with no serious ocular inflammation. Currently, Ixo-vec is being evaluated in the phase 3 ARTEMIS trial, which has completed screening.
“We believe Ixo-vec, if approved, will provide retina specialists and their wAMD patients with a compelling opportunity to preserve vision and reduce the need for lifelong injections,” said Fischer.