Archway phase 3 trial of the Port Delivery System with ranibizumab (PDS) for neovascular AMD: end-of-study results

Abstract

Purpose : The PDS is an innovative drug delivery system approved for neovascular age-related macular degeneration (nAMD) in the United States that includes an ocular implant for continuous delivery of a customized formulation of ranibizumab (RBZ) into the vitreous. The Archway trial (NCT03677934) evaluated safety and efficacy of the PDS for nAMD through 96 weeks (W).

Methods : Archway was a phase 3, randomized, active treatment–controlled trial. Patients (pts) with nAMD previously treated with and responsive to a mean of 5 anti–vascular endothelial growth factor injections were randomized 3:2 to PDS with RBZ 100 mg/mL with fixed 24W refill-exchanges (PDS Q24W), or intravitreal RBZ 0.5 mg injections every 4W (monthly RBZ) through W96. The trial evaluated noninferiority (NI) and equivalence of PDS Q24W versus monthly RBZ on a primary endpoint of best-corrected visual acuity (BCVA) change from baseline (BL) averaged over W36/40 (NI margin, –4.5 letters; equivalence margin, ±4.5 letters; previously presented) and key secondary endpoints of BCVA change from BL averaged over W60/64 and W88/92 (NI margin, –3.9 letters).

Results : PDS Q24W was noninferior to monthly RBZ at W60/64 and W88/92, with differences in adjusted mean (95% CI) BCVA change from BL of 0.4 (–1.4, +2.1) and –0.6 (–2.5, +1.3) letters between arms, respectively. Change in adjusted mean BCVA from BL averaged over W60/64 and W88/92, respectively, was –0.4 and –1.1 letters in the PDS Q24W arm and –0.8 and –0.5 letters in the monthly RBZ arm. Adjusted mean center point thickness change from BL was generally similar between arms through W96. During each of the 4 Q24W PDS treatment intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS pts assessed did not receive supplemental RBZ treatment, respectively. The ocular safety profile of the PDS was generally unchanged from the primary analysis, with no new safety signals.

Conclusions : Archway end-of-study results support the continued efficacy of the PDS over 2 years. Archway BCVA results averaged over W60/64 and W88/92 were consistent with the primary analysis, with PDS Q24W noninferior to monthly RBZ. Through each of the 4 Q24W PDS treatment intervals, ~95% of PDS pts assessed did not receive supplemental RBZ. Adverse events related to PDS procedures were well understood and manageable, with learnings continually implemented to optimize pt outcomes.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.