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David Callanan, Elizabeth Morgenthien, Natasha Singh, Giulio Barteselli; Port Delivery System with ranibizumab (PDS): Using Ladder phase 2 results to inform phase 3 Archway design. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5192.
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To address the need for a reduced treatment burden for the management of neovascular age-related macular degeneration (nAMD), the Port Delivery System with ranibizumab (PDS) was designed as a refillable, indwelling implant providing diffusion-mediated continuous intravitreal delivery of ranibizumab (RBZ).
The Ladder trial (NCT02510794) is evaluating the efficacy and safety of the PDS with 3 RBZ formulations compared with monthly intravitreal RBZ 0.5 mg injections for the treatment of nAMD. The primary study endpoint, defined as time to first required implant refill assessed when the last enrolled patient completed the month 9 visit, has been reached. The phase 3 Archway (NCT03677934) is an ongoing randomized clinical trial directly comparing PDS 100 mg/mL with fixed 24-week refills with intravitreal RBZ 0.5 mg monthly.
The Ladder primary analysis population was 220 patients: 59, 62, and 58 patients in the PDS 100, 40, and 10 mg/mL arms, respectively, and 41 patients in the monthly intravitreal RBZ arm. The median time to first refill was 15.0, 13.0, and 8.7 months with 79.8%, 71.3%, and 63.5% patients not meeting implant refill criteria until ≥ 6 months for the PDS 100, 40, and 10 mg/mL arms, respectively. At month 9, mean change in BCVA from baseline was +4.3, –0.5, –3.2, and +3.3 letters for PDS 100, 40, and 10 mg/mL, and monthly intravitreal RBZ arms, respectively. At the time of primary analysis, patients in the PDS 100, 40, and 10 mg/mL arms had received a mean total of 2.4, 2.6, and 3.7 RBZ treatments during a mean time on study of 16.4, 17.0, and 16.9 months, respectively, compared to a mean total of 16.8 RBZ treatments received by patients in the monthly intravitreal RBZ arm during 16.4 month mean time on study. The optimized PDS implant insertion surgery and refill procedures were well tolerated. Case examples from the Ladder study and mechanism of action of continuous delivery will be presented at the meeting.
With 80% of patients not needing an implant refill until ≥ 6 months in the PDS 100 mg/mL arm and comparable efficacy outcomes between PDS 100 mg/mL and monthly intravitreal RBZ treatment, Ladder results support the Archway design of PDS 100 mg/mL with fixed 24-week refills. PDS has the potential to reduce high intravitreal treatment burden and improve patient outcomes in clinical practice.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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