Abstract
Purpose :
The PDS is an innovative drug delivery system for continuous delivery of a customized formulation of ranibizumab. In the Pagoda trial for DME and the Pavilion trial for nonproliferative DR without center-involved DME, PDS with ranibizumab 100 mg/mL was investigated with fixed refill-exchanges every 24 weeks (PDS Q24W) and 36 weeks (PDS Q36W), respectively. Retinal nonperfusion and macular leakage are considered important biomarkers driving DME and DR clinical outcomes. Thus, effects of PDS on retinal nonperfusion area (NPA) and macular leakage area were evaluated.
Methods :
Pagoda (NCT04108156) and Pavilion (NCT04503551) are ongoing, phase 3, randomized, visual assessor–masked trials. In Pagoda, patients were randomized 3:2 to PDS Q24W or intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W). In Pavilion, patients were randomized 5:3 to PDS Q36W or control (clinical monitoring plus supplemental intravitreal ranibizumab 0.5 mg as required). Mean change from baseline in macular and 7-field ischemic NPA as well as macular leakage area were measured at week (W) 64 in Pagoda and W52 in Pavilion. NPA and macular leakage area (on fluorescein angiography) were assessed by masked reading centers.
Results :
Pagoda and Pavilion met their primary endpoints: PDS Q24W [n=381] was noninferior to ranibizumab Q4W [n=253] in BCVA change from baseline averaged over W60/W64, and PDS Q36W [n=106] was superior to control [n=68] in ≥2-step DRSS improvement from baseline at W52, respectively.
In Pagoda at W64, mean change from baseline in ischemic NPA was similar with PDS Q24W and ranibizumab Q4W in both macula and 7-field (Table). In Pavilion at W52, ischemic NPA remained unchanged from baseline with PDS Q36W but in the control arm increased from baseline in both macula and 7-field (Table).
In Pagoda at W64, there was a comparable improvement in macular leakage from baseline with PDS Q24W and ranibizumab Q4W (Table and Figure). In Pavilion, macular leakage analysis is currently ongoing.
Conclusions :
Continuous delivery with PDS has the potential to slow progression of macular and peripheral retinal nonperfusion in patients with DME and DR. Based on currently available analysis, PDS can also improve macular leakage in patients with DME.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.