Researchers assessed the safety and efficacy of the ranibizumab Port Delivery System (PDS) for neovascular AMD.
Study design
This phase 2, multicenter, randomized, active treatment-controlled clinical trial enrolled 220 patients within 9 months of their original diagnosis who were responsive to previous anti-VEGF injections. Patients were randomized to receive PDS with 10 mg/mL (n=58), 40 mg/mL (n=62) or 100 mg/mL (n=59) of ranibizumab or monthly ranibizumab injections (n=41).
Outcomes
The median time to first implant refill in the 10 mg/mL, 40 mg/mL and 100 mg/mL arms was 8.7, 13.0 and 15.0 months, respectively. The decision to refill was based on prespecified criteria indicating disease activity.
By month 9, the mean BCVA change from baseline was -3.2, -0.5, +5.0, and +3.9 letters in the PDS 10 mg/mL, 40 mg/mL, 100 mg/mL and monthly ranibizumab arms, respectively. Changes in central foveal thickness from baseline was similar between the PDS 100 mg/mL and monthly ranibizumab arms. Overall, the implantation and refill procedures were well tolerated.
Limitations
This was a promising phase 2 study, but a phase 3 trial is necessary to confirm safety and efficacy. Given the surgical nature of this device, there may be an increased risk of ocular adverse events compared with intravitreal injections. For example, vitreous hemorrhage occurred in 10.1% of patients, but the rate dropped to 4.5% after a modification to the surgical procedure. Three eyes had endophthalmitis and 5 had retinal detachment.
Clinical significance
The race is on for long-acting therapies for wet AMD, diabetic retinopathy, diabetic macular edema and retinal vein occlusion. The PDS may transform the clinical landscape from frequent injections to more of a surgical implantation scenario that reduces the frequency of office-based therapies. The phase 3 ARCHWAY clinical trial is currently underway and has recently completed enrollment.