Port Delivery System with Ranibizumab in Diabetic Macular Edema: Primary Analysis of the Phase 3 Pagoda Trial

Theme: Retina*
What: Retina
Part of: Retina II: Stamping out Blindness and Restoring Sight / Rétine II: Lutter contre la cécité et redonner la vue
When: 6/1/2024, 04:15 PM - 05:45 PM
Where: Room | Salle 713 AB

Abstract

Title:

Port Delivery System with Ranibizumab in Diabetic Macular Edema: Primary Analysis of the Phase 3 Pagoda Trial

Purpose:

The Port Delivery System with ranibizumab (PDS) is an innovative drug delivery system with a refillable ocular implant for continuous delivery of a customised formulation of ranibizumab into the vitreous. The phase 3 Pagoda trial is assessing the efficacy, safety and pharmacokinetics of the PDS with fixed 100 mg/mL refill-exchange procedures every 24 weeks (PDS) compared with intravitreal ranibizumab 0.5 mg injections every 4 weeks (RBZ) in patients with centre-involved diabetic macular edema (CI-DME). 

Methods:

Pagoda enrolled patients ≥18 years with CI-DME who were treatment-naïve or who had not received treatment for diabetic retinopathy or DME in the past 6 months. Inclusion criteria included best-corrected visual acuity (BCVA) of 25–78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/32 to 20/320 approximate Snellen equivalent), and central subfield thickness (CST) ≥325 µm. Eligible patients were randomised 3:2 to treatment with PDS or RBZ. Patients receiving PDS were assessed for the need for supplemental treatment with RBZ 0.5 mg at 2 visits before each refill-exchange. The prespecified primary endpoint was change in BCVA score (ETDRS letters) from baseline averaged over weeks (W) 60 and 64 using a non-inferiority margin of 4.5 letters. Additional efficacy endpoints included change from baseline CST and proportion of patients with ≥2-step improvement on the ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS). 

 

Results:

634 eyes were randomised (PDS, n=381; RBZ, n=253). Baseline demographics were balanced between arms. Primary endpoint of noninferiority met for mean change in BCVA from baseline averaged over W60 and W64 (in ETDRS letters [95% CI]: PDS, 9.6 [8.7, 1.5]; RBZ, 9.4 [8.3, 10.5]; difference [95% CI] 0.2 [–1.2, 1.6]). PDS resulted in CST reductions comparable to RBZ through W64 with change of –203.5 µm with PDS and –199.7 µm with RBZ. A clinically meaningful improvement in DRSS at W64 was also observed with 39% of PDS patients achieving ≥2-step improvement from baseline on ETDRS-DRSS compared with 41.9% in the RBZ arm, although noninferiority was not met (difference (95% CI): –2.9 (–10.7%, 4.9%); Noninferiority margin: –10.0%). Through 2 refill-exchange intervals, 95.9% and 97.4% of PDS patients assessed did not receive supplemental treatment, respectively. Additional secondary efficacy results will be presented. The PDS was well tolerated with no endophthalmitis cases and comparable systemic safety findings reported in the PDS arm through W64. 

Conclusion:

The PDS phase 3 Pagoda trial met its primary endpoint and demonstrated PDS Q24W resulted in vision outcomes at W60/64 that were noninferior to RBZ Q4W. PDS resulted in vision, anatomic and DRSS outcomes that were comparable to RBZ. The PDS was well tolerated, with no new safety signals.

Presenter(s)

Presenting Author: Shaheer Aboobaker

Additional Author(s):

Jordan Graff, Barnet Dulaney Perkins Eye Center at American Vision Partners, Phoenix, AZ; University of Arizona, Phoenix; Creighton University, Phoenix, AZ; American Vision Partners, Phoenix, AZ

Dennis Marcus, Southeast Retina Center and Medical College of Georgia, Augusta, GA

Peter Campochiaro, The Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Arshad Khanani, Sierra Eye Associates, Reno, NV, USA

---