Continuous Ranibizumab via Port Delivery System vs Monthly Ranibizumab for Treatment of Diabetic Macular Edema: The Pagoda Randomized Clinical Trial.

Abstract

Importance: Frequent visits and intravitreal anti-vascular endothelial growth factor (VEGF) injections are often required to manage diabetic macular edema (DME), burdening patients and their health care networks. The Port Delivery System (PDS) with ranibizumab is the first continuous anti-VEGF therapy that has the potential to reduce visit and treatment burden without sacrificing vision outcomes for patients with DME.

Objective: To evaluate the efficacy and safety through 64 weeks of ranibizumab, 100 mg/mL, via PDS with refill exchanges every 24 weeks (PDS Q24W) in patients with DME vs intravitreal injections of ranibizumab, 0.5 mg, every 4 weeks (monthly ranibizumab).

Design, setting, and participants: This randomized clinical trial was a phase 3, multicenter, noninferiority trial conducted across 87 sites in the US. Treatment-naïve patients at least 18 years old with center-involved DME were eligible for study participation. Enrollment was from September 30, 2019, to June 25, 2021; data were analyzed from September 30, 2019, to September 19, 2022.

Intervention: Participants were randomized 3:2 to receive 4 monthly doses of ranibizumab, 0.5 mg, followed by ranibizumab, 100 mg/mL, via PDS Q24W or monthly ranibizumab.

Main outcome and measure: The primary end point was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 60 and 64.

Results: A total of 634 participants were randomized (PDS Q24W group, n = 381; monthly ranibizumab, n = 253). The mean (SD) age at baseline was 60.7 (9.6) years; 363 (57.3%) participants were male and 271 (42.7%) female. Adjusted mean BCVA change from baseline averaged over weeks 60 and 64 was an increase of 9.6 letters for PDS Q24W and 9.4 letters for monthly ranibizumab (difference, 0.2; 95% CI, -1.2 to 1.6), meeting the primary end point of PDS noninferiority (margin, -4.5 letters). PDS Q24W participants had a mean (SD) decrease of 6.7 (12.0) letters 4 weeks after PDS insertion; mean BCVA was similar to monthly ranibizumab 16 weeks after implantation. Adverse events of special interest were more common in the PDS Q24W group (88 participants; 27.5%) than the monthly ranibizumab group (28 participants; 8.9%). No cases of endophthalmitis or retinal detachment were reported with PDS Q24W.

Conclusions and relevance: This trial found that changes in BCVA from baseline averaged over weeks 60/64 in the PDS Q24W group were comparable to the monthly ranibizumab group. While AESIs were more common with PDS Q24W, there were no instances of endophthalmitis or retinal detachment. Continuous ranibizumab, 100 mg/mL, via PDS was approved in the US for patients with DME in February 2025 and provides effective, durable, and generally well-tolerated treatment for DME with retreatment every 6 months through at least 64 weeks.

Trial registration: ClinicalTrials.gov Identifier: NCT04108156.