Ranibizumab port delivery system: a clinical perspective

Abstract

Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. Neovascular AMD (nAMD) is a subtype of AMD most frequently treated with intravitreal anti-vascular endothelial growth factor (aVEGF) injections, which has allowed for patients to maintain vision that would have otherwise been lost. However, the need for frequent intravitreal injections for optimal results poses a risk for undertreatment in nAMD patients due to the high treatment burden associated with current aVEGF therapy. Many novel agents and pathways are being explored and targeted for less burdensome treatment options, one of which is the ranibizumab port delivery system (PDS). The PDS is a surgically implanted, refillable device that allows for the sustained release of ranibizumab, a widely used aVEGF agent, into the vitreous cavity. Positive results non-inferior to monthly ranibizumab injections in both phase II and phase III clinical trials allowed for FDA approval of the device with refill intervals of 6 months, which represents the longest approved treatment interval to date for nAMD therapy. This article reviews the need for a durable nAMD treatment option in real-world practice, the clinical trial and extension study data for the PDS, the risk of adverse events and safety profile of the PDS and the potential clinical role of the PDS in answering the real-world needs of nAMD treatment. In addition, other pipeline sustained-treatment modalities are discussed in the context of ongoing clinical trials.

Injectable Devices for Delivery of Liquid or Solid Protein Formulations

“…Given its recent voluntary recall, there is clearly a need for minimally invasive sustained drug delivery devices. , Ozurdex and its corresponding 22-gauge thin-walled injector provide the current standard for maximum tolerated device size. Ozurdex and Iluvien have lengths of 6 and 3.5 mm, respectively, and the Port Delivery System has an overall length of 8.4 mm. ,, Given these reference points, acceptable device length should be 8 mm or smaller, which is expected to avoid interference with the visual axis.…”

“…Ophthalmology has long been a target for drug delivery technology development given the rapid surface clearance and physical barriers to drug delivery. , With the advent of anti-VEGF therapeutics requiring regular injections for the treatment of retinal disease, the field has pursued delivery solutions to reduce clinician burden while improving patient comfort and compliance. The Port Delivery System (PDS), developed specifically for sustained delivery of ranibizumab, achieved FDA approval in 2021 and represents the first sustained-delivery device for an ocular protein therapeutic . Placed in the vitreous and anchored to the sclera by a surgical procedure, the PDS enables patients to receive a single dose of concentrated ranibizumab (100 mg/mL) with a prescribed refill every 24 weeks, and an external port allows access for refilling upon depletion .…”

“…For any given biologic, physical and chemical stability, tendency for aggregation, or freeze–thaw behavior must all be investigated and may require formulation optimization to mitigate any shortcomings . Processes of denaturing, fragmentation, and aggregation can be impacted by protein concentrations, solution pH or osmolarity, solvent–protein interactions, or even physical pressure. , Whether administered by injection, with a metered pump, or a permanent implant, delivery of biologics commonly relies on aqueous formulations of drug, where preparation of the administered drug is separated from its mode of delivery.…”

“…7 Processes of denaturing, fragmentation, and aggregation can be impacted by protein concentrations, solution pH or osmolarity, solvent−protein interactions, or even physical pressure. 8,9 tered by injection, 10 with a metered pump, 11 or a permanent implant, 12 delivery of biologics commonly relies on aqueous formulations of drug, where preparation of the administered drug is separated from its mode of delivery. Intravenous or subcutaneous administration is well suited for systemic delivery of liquid formulations of biologics as it accommodates the large mass of drug required for systemic therapy.…”

Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration

“…PDS is applied through the surgical insertion of the device into the scleral space through conjunctival peritomy. After implantation, the drug diffuses from the release control element in a sustained manner into the vitreous, which can be filled again once emptied [ 136 ]. A phase 2 trial of PDS of ranibizumab (10 to 100 mg/mL) was conducted for assessing its safety and efficacy.…”