Port Delivery System offers new paradigm for longer-acting retinal therapies
The Port Delivery System continuously and reproducibly delivers ranibizumab over a period of at least 6 months, as shown in studies presented at the virtual Association for Research in Vision and Ophthalmology meeting.
“In vitro results support the fixed 24-week refill-exchange intervals in the Archway trial, where PDS Q24W showed to deliver vision and anatomic outcomes comparable to Q4W intravitreal ranibizumab injections,” Jay Stewart, MD, said.
The Port Delivery System (PDS, Genentech) contains a customized formulation of ranibizumab 100 mg/mL, a 10 times higher concentration than that used in intravitreal injections. It is intentionally designed to remain in the eye after implantation and to be refilled through a self-sealing septum, using a proprietary refill needle.
“Ranibizumab release from the PDS implant is mediated by passive diffusion. Ranibizumab molecules move from the area of high concentration in the implant to low concentration in the vitreous cavity along a concentration gradient. The rate of diffusion is dependent on the ranibizumab concentration in the implant and decreases over time,” Stewart said.
In vitro studies showed that the release rate changes gradually from about 17 µg per day to 4 µg per day due to continuously decreasing ranibizumab concentration inside the implant. These release rates ensure that the drug concentration in the vitreous is maintained within therapeutic levels.
The same studies demonstrated that, following the initial fill, 50% of the drug is released after 100 days and 70% is released over 6 months. Release rates after refill-exchange are consistent with the initial fill, ensuring that the drug concentration in the vitreous is maintained within therapeutic levels across 24-week treatment cycles.
The refill procedure is performed in-office, Stewart said.
“The proprietary needle allows any residual implant content to be extracted simultaneously as the implant is refilled with fresh ranibizumab in a single stroke,” he said.
In the Archway phase 3 clinical trial, the safety and efficacy of PDS with fixed refill-exchange every 24 weeks were compared with monthly ranibizumab injections for neovascular AMD. Continuous ranibizumab release resulted in consistent clinical outcomes across treatment cycles.
“At the primary endpoint, the PDS Q24W was noninferior and equivalent for BCVA change at average of weeks 36 to 40. The BCVA change at average of weeks 44 to 48 remained noninferior thorough two refill-exchange intervals. Central point thickness outcomes were comparable across arms,” Stewart said.
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Stewart J, et al. The Port Delivery System with ranibizumab (PDS) — a new paradigm for long-acting retinal drug delivery. Presented at: Association for Research in Vision and Ophthalmology annual meeting; May 1-7, 2021 (virtual meeting).
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