Port delivery system release is predictable and adaptable for nAMD processing

The recently approved new port delivery system (PDS) for ranibizumab (Lucentis) has been shown to provide consistent, predictable and even tunable delivery of anti-VEGF therapy into the retina of patients with neovascular macular degeneration related at age (nAMD), according to new research.

In a new trial presented at the Association for Research in Vision and Ophthalmology (ARVO) 2022 meeting over the weekend, a team of Genentech researchers showed data suggesting that PDS could be a flexible method and even patient-tailored for standard-of-care anti-VEGF treatment delivery to patients, even beyond ranibizumab.

The United States Food and Drug Administration (FDA) initially approved PDS with ranibizumab for the treatment of adults with nAMD in October 2021. The device is a surgically implanted permanent treatment port that directly and continuously provides treatment to the affected eyes of patients. It requires six-monthly “filler” administrations, but eventually ends the need for continuous intravitreal injection administrations.

A Genentech-sponsored team of researchers, led by Principal Scientist Judit Horvath, PhD, conducted a in vitro evaluation to verify the modeled drug release kinetics of a PDS implant, which is controlled by the porous release control element (RCE) via passive diffusion. The team reported the effects of various PDS drug and implant parameters in patients at ARVO 2022.

Horvath and colleagues determined release rate profiles of PDS implants as a function of implant loading parameters and device half-life. Implant loading was defined by drug concentration and implant volume, while SDP half-life depended on the porosity and dimensions of the NCE, the drug diffusion coefficient, and the volume of the implant. ‘implant. The team mimicked ocular drug clearance and sought to maintain similar PDS release kinetics by regularly transferring drug-filled implants to new vials containing buffer.

Released drug concentrations were measured via concentration assays, and release rate data were fitted by an exponential model that mimicked the expected release kinetics of diffusion. The team compared the data with predicted release rate kinetics.

Investigators observed a decrease in PDS release rate over time, while changing the initial ranibizumab concentration from 10 mg/mL to 150 mg/mL increased baseline drug release rates by 1.75 at 25.2 mcg per day, respectively; the observed release of ranibizumab closely tracked the team’s model predictions over a 6-month period, demonstrating its predictability.

Although the current volume of the PDS implant is set at 20 mcL, the team evaluated a range of volumes from 10 to 100 mcL. “In model predictions for ranibizumab 100 mg/mL, initial drug release is consistent at 13.9-14.5 mcg/day across different implant volumes, with drug release at 6 months ranging from 1 mcg /day (10 mcL implant) to 11 mcg/day (100 mcL implant),” they reported.

While the PDS implant is optimized for ranibizumab release – with an RCE Release Rate Index (RRI) of 0.024 mm – the researchers observed that the RCE pore size modification of the drug diffusion coefficient had a significant impact on implant half-life; decreasing the IRR from 0.024 to 0.008 mm increased the half-life from 14 to 42 weeks in evaluations with ranibizumab 100 mg/mL.

“Drug release from the PDS implant was found to be highly predictable and tunable based on a simple diffusion model,” the researchers concluded. “The port delivery system offers flexible platform technology, with the ability to tailor implant release kinetics by carefully selecting drug molecule, drug concentration, and specific implant parameters. “

The study, “Drug release kinetics of the Port Delivery System with ranibizumab (PDS): technology platform for continuous retinal drug delivery,” was presented at ARVO 2022.

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