medwireNews: The Port Delivery System (PDS) with ranibizumab has the potential to reduce the burden of treatment for patients with neovascular age-related macular degeneration (nAMD), suggest findings from the phase II Ladder trial.
When compared with monthly intravitreal administration of ranibizumab 0.5 mg, PDS administration of ranibizumab 100 mg/mL was as effective in maintaining vision outcomes at 9 months but resulted in patients receiving around 80% fewer ranibizumab treatments.
“[T]hese results suggest that the PDS is a good candidate to change the treatment paradigm in nAMD and respond to the current unmet need to reduce treatment burden while maintaining or improving patient outcomes”, say Peter Campochiaro (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) and co-researchers.
The system involves a permanent, refillable implant that is surgically inserted through a small incision in the sclera and pars plana and has a self-sealing septum to allow drug replenishment. This technique means passive diffusion can occur, resulting in controlled continuous drug release into the vitreous over time.
In all, 220 patients were randomly assigned and treated with PDS ranibizumab, at doses of 10 mg/mL, 40 mg/mL and 100 mg/mL, or monthly intravitreal ranibizumab 0.5 mg injections.
The median time to the first PDS implant refill was 8.7 months for patients in the 10 mg/mL group, 13.0 months in the 40 mg/mL group and 15.0 months in the 100 mg/mL group.
Indeed, most of the patients did not need an implant refill for at least 6 months, at a respective 63.5%, 71.3% and 79.8%.
Over a mean treatment time of about 16 months, the patients in the PDS ranibizumab 10, 40 and 100 mg/mL groups had received an average of 3.7, 2.6 and 2.4 treatments, respectively, compared with 16.8 in the intravitreal ranibizumab group.
The researchers point out that this reduction in treatment burden did not come at the cost of clinical efficacy, however. The patients, who were already receiving and responsive to treatment prior to the analysis, maintained a good baseline best-corrected visual acuity (BCVA) at 9 months irrespective of treatment delivery.
There was a dose-dependent change in BCVA in the PDS ranibizumab arms, of –3.2 ETDRS letters with 10 mg/mL, –0.5 with 40 mg/mL and +0.5 with 100 mg/mL. And this change was comparable to the +3.9 ETDRS letter change seen with intravitreal administration of ranibizumab 0.5 mg.
Similarly, central foveal thickness was maintained in all ranibizumab treatment groups and to a comparable degree in the PDS 100 mg/mL and monthly intravitreal arms.
The systemic safety profile of the PDS system was generally comparable to that of intravitreal injection, but serious ocular adverse events were more frequent, affecting 8.9% of patients.
The most commonly occurring event was vitreous haemorrhage, occurring in 4.5% of 157 evaluable PDS patients. The team explains that the PDS surgical technique did have to be revised early in the trial to include laser ablation of the pars plana at the incision site after finding that this was a major cause of bleeding.
They conclude in Ophthalmology: “The results from the phase 2 Ladder trial provide a glimpse of how treatments for nAMD and other retinal vascular diseases, including diabetic eye disease and retinal vein occlusion, may evolve in the future. The next step in this evolution of PDS for nAMD is the pivotal Archway phase 3 trial.”
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