Abstract
Purpose :
The PDS is an innovative, investigational, intraocular drug delivery system with the potential to reduce treatment burden in patients with retinovascular diseases. The PDS implant is a permanent, indwelling device designed to continuously deliver a customized formulation of ranibizumab. The PDS refill needle consists of a dual cannula system that allows for simultaneous exchange of implant contents with fresh drug. The characterization of ranibizumab release and refill-exchange efficiency of the PDS is reported here.
Methods :
The ranibizumab release rate, active release rate, and retained ranibizumab within the implant over time were measured in vitro with various starting concentrations of ranibizumab. In the ongoing phase 3 Archway trial (NCT03677934) for neovascular AMD, PDS 100 mg/mL with fixed Q24W refill-exchanges was compared with intravitreal ranibizumab 0.5 mg Q4W.
Results :
The PDS includes a surgically placed, permanent implant and ancillary devices for implant insertion, initial fill, and in-clinic refill-exchange procedures. The PDS implant was designed to be biocompatible; durable; transparent to facilitate visualization of ranibizumab within the implant; have a self-sealing, refillable septum; not interfere with the patient’s field of vision; and be implanted in the superotemporal quadrant. In in vitro studies, ~73% of ranibizumab 100 mg/mL was released from the implant over 6 months after initial implant insertion and after ~450 days, levels were below the lower quantification limit. The average active release rate (SD) at 6 months was 3.95 (0.17), 3.99 (0.13), 3.85 (0.15), and 4.00 (0.17) µg/day at initial fill, first, second, and third refills, respectively, demonstrating reproducibility from implant to implant and between multiple refill-exchanges of the same implant. Changing initial ranibizumab concentration from 10 to 100 mg/mL increased starting drug release rates from ~2 to ~17 µg/day and rate of release. During a refill-exchange procedure, ~98% of the previous implant contents get replaced with fresh drug in one 100-µL injection stroke.
Conclusions :
The PDS is an intraocular drug delivery system that continuously and reproducibly delivers ranibizumab over a period of months while maintaining potency. Archway phase 3 trial results support the efficacy of the PDS, as PDS 100 mg/mL Q24W had equivalent vision outcomes to ranibizumab Q4W averaged over weeks 36/40.
This is a 2021 ARVO Annual Meeting abstract.