Port Delivery System with ranibizumab (PDS) met primary endpoint and key secondary outcomes with > 75% of patients preferring PDS treatment in phase 3 Pavilion trial for diabetic retinopathy (DR)

Abstract

Purpose : The PDS is an innovative drug delivery system for continuous delivery of a customized formulation of ranibizumab. Pavilion is the first trial to evaluate the efficacy, safety, and pharmacokinetics of PDS 100 mg/mL with fixed refill-exchanges every 36 weeks (Q36W) in patients with DR without center-involved diabetic macular edema (CI-DME).

Methods : Pavilion (NCT04503551) is an ongoing phase 3, multicenter, randomized, visual assessor–masked trial. Patients were randomized (5:3) to receive PDS Q36W or control (clinical monitoring plus supplemental intravitreal ranibizumab 0.5 mg as required), respectively. Patients could receive supplemental intravitreal ranibizumab 0.5 mg at each study visit (control) or any non–refill-exchange visit (PDS Q36W). Primary endpoint: proportion of patients with a ≥2-step ETDRS-DRSS improvement from baseline at week (W) 52. Additional efficacy endpoints: rate of patients developing CI-DME; and assessment of treatment preference for PDS vs intravitreal injections in PDS Q36W patients using the PDS Patient Preference Questionnaire at W52.

Results : 174 patients were randomized (PDS Q36W, n=106; control, n=68). Pavilion met its primary endpoint in superiority of PDS Q36W; a significantly greater proportion of patients achieved a ≥2-step ETDRS-DRSS improvement from baseline with PDS Q36W (80.1%) vs control (9.0%) at W52 (difference=71.1%; 95% CI, 61.0–81.2; P=<0.0001). The rate of patients developing CI-DME was significantly lower with PDS Q36W (7.1%) vs control (47.0%) at W52 (hazard ratio=0.1; 95% CI, = 0.1–0.3; P=<0.0001). Through W52, no PDS Q36W patients received supplemental treatment compared with 39.7% of patients in the control arm. Overall, 76.6% (72/94) of PDS Q36W patients indicated a preference for PDS treatment at W52, with fewer treatments cited as the main reason (Fig 1). PDS was generally well tolerated. No events of endophthalmitis or implant dislocation were reported in the PDS arm through W52.

Conclusions : Pavilion met its primary endpoint; PDS Q36W demonstrated superior disease outcomes vs the control arm. More than 75% of patients preferred PDS treatment over intravitreal injections. No new safety signals were observed. PDS has the potential to provide clinical benefits without the need for frequent intravitreal injections in patients with DR.

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