Port Delivery System With Ranibizumab (PDS) in diabetic macular edema (DME): additional primary analysis results of the phase 3 Pagoda trial

Abstract

Purpose : The PDS is an innovative drug delivery system that includes a refillable ocular implant for continuous delivery of a customized formulation of ranibizumab. The Pagoda trial assesses the efficacy, safety, and pharmacokinetics of the PDS with fixed 100 mg/mL refill-exchanges every 24 weeks (Q24W) compared with intravitreal ranibizumab 0.5 mg injections every 4 weeks (RBZ Q4W) in patients with center-involved DME.

Methods : Pagoda (NCT04108156) is an ongoing phase 3, multicenter, randomized, visual assessor–masked, active comparator clinical trial. Patients were randomized 3:2 to PDS Q24W or RBZ Q4W. PDS Q24W patients were assessed for supplemental intravitreal ranibizumab 0.5 mg treatment at the 2 visits before each refill-exchange. Primary endpoint was change in BCVA score (Early Treatment Diabetic Retinopathy Study letters) from baseline averaged over weeks (W) 60 and 64 (noninferiority margin –4.5 letters). Additional efficacy endpoints included assessment of treatment preference for PDS vs intravitreal injections in PDS Q24W patients using the PDS Patient Preference Questionnaire at W64; and evaluation of the proportion of patients with absence of intraretinal fluid (IRF) and subretinal fluid (SRF) over time.

Results : 634 eyes were randomized (PDS Q24W, n=381; RBZ Q4W, n=253). Pagoda met its primary endpoint with PDS Q24W noninferior to RBZ Q4W for BCVA change from baseline averaged over W60/W64 (mean change, letters [95% CI]: PDS Q24W, 9.6 [8.7, 1.5]; RBZ Q4W, 9.4 [8.3, 10.5]; difference [95% CI] 0.2 [–1.2, 1.6]). CST reductions through W64 were comparable between arms. Through 2 refill-exchange intervals, 95.9% and 97.4% of PDS patients assessed did not receive supplemental treatment, respectively. Overall, 80% (241/301) of PDS Q24W patients indicated preference for PDS treatment at W64, with fewer treatments cited as the main reason (Fig 1). Absence of IRF and SRF in the central 1 mm subfield was comparable between arms at W64. PDS was generally well tolerated. No endophthalmitis cases were reported in the PDS arm after implantation through W64.

Conclusions : Pagoda met its primary endpoint – PDS Q24W demonstrated noninferior vision outcomes to RBZ Q4W at W60/64. PDS Q24W resulted in vision and anatomic outcomes comparable to RBZ Q4W with 80% of patients preferring PDS treatment.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Fig 1