Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration

Holekamp, Nancy M.; Campochiaro, Peter A.; Chang, Margaret; Miller, Daniel M.; Pieramici, Dante J.; Adamis, Anthony P.; Brittain, Christopher; Evans, Erica; Kaufman, Derrick; Maass, Katie F.; Patel, Shienal; Ranade, Shrirang; Singh, Natasha; Barteselli, Giulio; Regillo, Carl D.; Investigators, all Archway

doi:10.1016/j.ophtha.2021.09.016

Cited by 133 publications

(161 citation statements)

References 26 publications

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“…Port delivery systems have gone one step further, reporting results of patients requiring office refills every 6 months (or even longer). 48 , 49 …”

Section: Sustained Drug Delivery Platformsmentioning

confidence: 99%

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Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options

Tan¹,

Ngo²,

Chay³

et al. 2022

OPTH

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Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development.

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“…Port delivery systems have gone one step further, reporting results of patients requiring office refills every 6 months (or even longer). 48 , 49 …”

Section: Sustained Drug Delivery Platformsmentioning

confidence: 99%

“…Ocular adverse events in the PDS group included 4 cases of (1.6%) endophthalmitis, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions. 49 …”

Section: Sustained Drug Delivery Platformsmentioning

confidence: 99%

Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options

Tan¹,

Ngo²,

Chay³

et al. 2022

OPTH

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“…These include Susvimo , a surgically fixed permanent refillable implant, for the continuous release of the ranibizumab, a monoclonal antibody against vascular endothelial growth factor (anti-VEGF) to treat neovascular AMD [ 105 ]. The device provides 6 months of sustained drug release, replacing monthly intraocular injections [ 106 ]. Interestingly, it is the first IDDS to deliver monoclonal antibodies.…”

Section: Iddss and Fbr: Current Clinical Landscapementioning

confidence: 99%

Implantable Drug Delivery Systems and Foreign Body Reaction: Traversing the Current Clinical Landscape

et al. 2021

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Precise delivery of therapeutics to the target structures is essential for treatment efficiency and safety. Drug administration via conventional routes requires overcoming multiple transport barriers to achieve and maintain the local drug concentration and commonly results in unwanted off-target effects. Patients’ compliance with the treatment schedule remains another challenge. Implantable drug delivery systems (IDDSs) provide a way to solve these problems. IDDSs are bioengineering devices surgically placed inside the patient’s tissues to avoid first-pass metabolism and reduce the systemic toxicity of the drug by eluting the therapeutic payload in the vicinity of the target tissues. IDDSs present an impressive example of successful translation of the research and engineering findings to the patient’s bedside. It is envisaged that the IDDS technologies will grow exponentially in the coming years. However, to pave the way for this progress, it is essential to learn lessons from the past and present of IDDSs clinical applications. The efficiency and safety of the drug-eluting implants depend on the interactions between the device and the hosting tissues. In this review, we address this need and analyze the clinical landscape of the FDA-approved IDDSs applications in the context of the foreign body reaction, a key aspect of implant–tissue integration.

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“…The requirement for frequent injections of anti-VEGF therapy reflects the short intraocular half-life of these biologic agents, and the development of long-acting ocular drug delivery strategies has proved difficult (reviewed in Kim and Woo ( 2021 )). Despite advances in the field, only a few technologies have been assessed in clinical trials, and only one, the Port Delivery System with ranibizumab (PDS; commercially available as Susvimo, Genentech, Inc., South San Francisco, CA), has progressed to late-stage investigation and subsequent approval from the US Food and Drug Administration (FDA; Kim and Woo, 2021 ; Clinicaltrials.gov, 2021b ; Holekamp et al., 2022 ; Susvimo [package insert], 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Archway (NCT03677934) was a phase 3 randomized open-label trial of the PDS in patients with nAMD (Clinicaltrials.gov, 2021b ). Archway met its primary endpoint, demonstrating that PDS 100 mg/mL with fixed refill-exchanges every 6 months was both clinically equivalent and noninferior to monthly intravitreal ranibizumab 0.5 mg injections in terms of vision at the average of weeks 36 and 40 (Holekamp et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery

Ranade¹,

Wieland

Tam³

et al. 2022

Drug Delivery

Self Cite

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The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. The PDS includes an ocular implant, a customized formulation of ranibizumab, and four dedicated ancillary devices for initial fill, surgical implantation, refill-exchange, and explantation, if clinically indicated. Ranibizumab is an ideal candidate for the PDS on account of its unique physicochemical stability and high solubility. Controlled release is achieved via passive diffusion through the porous release control element, which is tuned to specific drug characteristics to accomplish a therapeutic level of ranibizumab in the vitreous. To characterize drug release from the implant, release rate was measured in vitro with starting concentrations of ranibizumab 10, 40, and 100 mg/mL, with release of ranibizumab 40 and 100 mg/mL found to remain quantifiable after 6 months. Using a starting concentration of 100 mg/mL, active release rate at approximately 6 months was consistent after the initial fill and first, second, and third refills, demonstrating reproducibility between implants and between multiple refill-exchanges of the same implant. A refill-exchange performed with a single 100-µL stroke using the refill needle was shown to replace over 95% of the implant contents with fresh drug. In vitro data support the use of the PDS with fixed refill-exchange intervals of at least 6 months in clinical trials.

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Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration

Cited by 133 publications

References 26 publications

Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options

Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options

Implantable Drug Delivery Systems and Foreign Body Reaction: Traversing the Current Clinical Landscape

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery

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