Necessary Disruption: Novel Anti-VEGF Delivery System Aims to Reshape AMD Treatment

In multiple clinical studies over the past two decades, anti–vascular endothelial growth factor (VEGF) therapy has led to dramatic improvements in the vision of patients with neovascular age-related macular degeneration (nAMD). However, it hasn't always been so easy for ophthalmologists to obtain such positive results in their own practices. Getting real-world patients to adhere to a set schedule of anti-VEGF injections can be a challenge that, if not surmounted, can eventually contribute to indolent visual decline. This has led to the search for alternative, less burdensome means of delivering anti-VEGF therapy.

A Novel System Shows Encouraging Results

Results from the randomized phase 2 Ladder trial evaluated the safety and efficacy of one such option, a surgically implanted port delivery system (PDS) with ranibizumab. The PDS features a permanent implant that can be refilled as needed, without the need to remove it from the eye.

Investigators recruited patients with nAMD who had demonstrated response to at least two prior anti-VEGF intravitreal injections, and had a best corrected visual acuity of 20/20 to 20/200. The 220 eligible patients were then randomly assigned to one of three PDS treatment arms with ranibizumab—10 mg/mL, 40 mg/mL, or 100 mg/mL—or monthly intravitreal injections of ranibizumab 0.5 mg.

All patients in the PDS treatment arms were evaluated monthly for increased nAMD activity that met preestablished criteria for implant refill, including an increase in central foveal thickness (CFT) ≥ 75 μm on spectral-domain optical coherence tomography or a decrease of five or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters.

The median time to first implant refill was 8.7, 13.0, and 15.0 months in the PDS 10 mg/mL, 40 mg/mL, and 100 mg/mL arms, respectively. At month 9, the adjusted mean best corrected visual acuity change from baseline in the PDS 10 mg/mL, 40 mg/mL, and 100 mg/mL arms and the monthly intravitreal injection arm was -3.2, -0.5, 5.0, and 3.9 ETDRS letters, respectively. Adjusted mean CFT change from baseline to 9 months (excluding pigment epithelial detachment height) was 54.4 μm, -0.5 μm, -1.7 μm in the PDS 10 mg/mL, 40 mg/mL, and 100 mg/mL arms, respectively, and -6.3 μm in the monthly intravitreal injection arm.

Overall, the PDS 100 mg/mL arm demonstrated vision and anatomical outcomes similar to those in the monthly intravitreal ranibizumab injection arm, while decreasing the number of ranibizumab treatments by roughly 80%.

The overall rate of ocular adverse effects in the PDS groups was 8.9% and did not result in severe vision loss. At the beginning of the study, 11 of the first 22 (50%) PDS-treated patients experienced vitreous hemorrhage, which led to the development of an optimized surgical procedure that incorporated pars plana laser ablation before making the incision. After implementation of this modified implant insertion procedure, 7 of 157 (4.5%) PDS-treated patients experienced vitreous hemorrhage, of which only one event was considered serious.

What Lies Ahead for PDS?

If approved, sustained VEGF suppression with a PDS has the potential to drastically change the current treatment paradigm of pulsatile VEGF suppression. We eagerly await results from Archway, the pivotal phase 3 clinical trial of PDS in nAMD. This trial will provide further evidence of whether visual outcomes are indeed improved over what is often observed in real-world settings, where many patients are noncompliant with frequent injections.

Any safe and effective means of lessening the treatment and follow-up burden on patients and their families, while maintaining vision outcomes, would certainly be welcomed.

Sophie J. Bakri, MD, a long-time contributor to Medscape, specializes in diseases and surgery of the retina and vitreous, including age-related macular degeneration. She also undertakes both clinical and translational research in the pathogenesis and treatment of retinal diseases.

Blake H. Fortes, MD, is currently a resident physician in the department of ophthalmology at the Mayo Clinic in Rochester, Minnesota.

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