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Ladder Phase 2 Trial of the Port Delivery System With Ranibizumab (PDS) for Neovascular AMD: End of Study Results

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Abstract Number: 1155

AuthorBlock: Franco Recchia1, Steven Blotner2, Natasha Singh2, Giulio Barteselli2, Shamika Gune2
1Tennessee Retina, Nashville, Tennessee, United States; 2Genentech, Inc, South San Francisco, California, United States;

DisclosureBlock: Franco Recchia, Adverum Code F (Financial Support), Aerpio Code F (Financial Support), Apellis Code F (Financial Support), Aura Biosciences Code F (Financial Support), Chengdu Kanghong Code F (Financial Support), Mylan Code F (Financial Support), National Eye Institute Code F (Financial Support), Novartis Code F (Financial Support), PanOptica Code F (Financial Support), Regeneron Code F (Financial Support), Roche/Genentech Code F (Financial Support), Syneos Health Code F (Financial Support), Steven Blotner, Genentech, Inc Code E (Employment), Natasha Singh, Genentech, Inc Code E (Employment), Giulio Barteselli, Genentech, Inc Code E (Employment), Shamika Gune, Genentech, Inc Code E (Employment)

Purpose
The PDS is an investigational drug delivery system designed for the continuous intravitreal release of ranibizumab through a permanent indwelling intraocular implant. The safety and efficacy of the PDS for the treatment of neovascular age-related macular degeneration (nAMD) was evaluated in the phase 2 Ladder trial.

Methods
The Ladder trial (NCT02510794) compared the PDS filled with 3 different customized ranibizumab formulations with monthly intravitreal ranibizumab 0.5 mg. The primary endpoint was time to first implant refill according to protocol-defined criteria assessed when the last enrolled patient completed the month (M) 9 visit. Secondary outcomes included mean change from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT). All patients continued on assigned study treatment until they were eligible to roll over into the Portal extension study (NCT03683251).

Results
Ladder evaluated 220 patients, with 58, 62, 59, and 41 patients in the PDS 10, 40, and 100 mg/mL and monthly intravitreal ranibizumab 0.5 mg arms, respectively. The mean time on study was 22.1M (range, 10.8M-37.6M) for all PDS patients. The median time to first required refill was 8.7M, 13.0M, and 15.8M for the PDS 10, 40, and 100 mg/mL arms, respectively. In the PDS 100 mg/mL arm, 59.4% of patients went ≥12M without meeting refill criteria. In PDS 100 mg/mL patients who met implant refill criteria at least once, the median time to first and second refills was consistent: first refill, 8.8M (n=31/59); second refill, 8.8M (n=19/31). At M22 in the PDS 100 mg/mL and monthly ranibizumab 0.5 mg arms, respectively, the mean BCVA change from baseline was +2.9 and +2.7 letters, and 87.5% and 88.9% of patients maintained vision (lost <5 letters from baseline). Mean CFT change from baseline excluding pigment epithelial detachment height was generally similar between the PDS 100 mg/mL and monthly ranibizumab 0.5 mg arms. No dose-related serious AEs were observed.

Conclusions
Ladder end of study efficacy and safety outcomes were consistent with the primary analysis. PDS 100 mg/mL continuously maintained vision and anatomic outcomes through a mean time on study of 22M. The optimized implant insertion procedure and refill procedure were generally well tolerated. The PDS has potential to reduce high intravitreal treatment burden and improve real-world clinical outcomes.

Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details.
The Port Delivery System with ranibizumab (PDS) is an investigational drug delivery system for the treatment of wet age-related macular degeneration (wet AMD) and is intended to reduce the burden of monthly eye injections. The PDS includes a refillable implant inserted into the eye and allows the continuous release a special form of ranibizumab, a medication already FDA-approved for the treatment of wet AMD. The PDS implant can be refilled in the office. The phase 2 Ladder trial compared the PDS pre-filled with 3 different formulations of ranibizumab against monthly ranibizumab 0.5 mg eye injections. In Ladder, patients received implant refills when needed, based on changes in vision or severity of the wet AMD. Almost 60% of patients treated with the PDS filled with the most-concentrated formulation (100 mg/mL) did not need an implant refill for over a year (≥12 months), with the median time to first refill being 15.8 months. In the Ladder trial, the improvements in vision obtained with the PDS were similar to those seen with monthly injections of ranibizumab. The PDS has the potential to reduce or avoid the need for monthly eye injections.