A Phase 1, Open-Label, Dose-Escalation Trial to Investigate Safety and Tolerability of Single Intravitreous Injections of ICON-1 Targeting Tissue Factor in Wet AMD

Wells, John A.; Gonzales, Christine R.; Berger, Brian B.; González, Víctor H.; Sippy, Brian D.; Burian, Gabriela

doi:10.3928/23258160-20180501-07

Cited by 12 publications

(3 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Basically, it consists of two identical chains of proteins: human Factor VII (fVII) as the targeting domain and human immunoglobulin G1 Fc as the effector domain, functioning as binding to pathological vessels overexpressing tissue factor ( Bora et al, 2003 ; Tezel et al, 2007 ). Although intravitreous administration of a single 0.3 mg dose of ICON-1 was safe and well tolerated, its biological activity was evident in a Phase I clinical trial ( Wells et al, 2018 ), and the results reported from a Phase II clinical trial (NCT02358889) with improved BCVA as the primary outcome showed that hl-con1 0.3 mg in combination with ranibizumab 0.5 mg did not surpass ranibizumab 0.5 mg monotherapy. Another phase II trial (NCT03452527) showed that the CNV size assessed by OCT angiography in the ICON-1 0.6 mg maintenance therapy group did not exceed that in the ICON-1 0.6 mg combination therapy group (with aflibercept 2 mg).…”

Section: Clinical Trials Of Therapies For Nvamdmentioning

confidence: 99%

Rethinking the potential and necessity of drug delivery systems in neovascular age-related macular degeneration therapy

Huang

Zhang

et al. 2023

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is the predominant threat to human vision and ultimately results in blindness. With the increase in the aging population, it has become a more crucial issue to human health. AMD is a multifactorial disease with the unique feature of uncontrollable angiogenesis during initiation and progression. Although increasing evidence indicates that AMD is largely hereditary, the predominant efficient treatment is antiangiogenesis, which mainly involves VEGF and HIF-α as therapeutic targets. The repeated administration of this treatment over the long term, generally through intravitreal injection, has called for the introduction of long-term drug delivery systems, which are expected to be achieved by biomaterials. However, the clinical results of the port delivery system indicate that the optimization of medical devices toward prolonging the activities of therapeutic biologics in AMD therapy seems more promising. These results indicate that we should rethink the possibility and potential of biomaterials as drug delivery systems in achieving long-term, sustained inhibition of angiogenesis in AMD therapy. In this review, the etiology, categorization, risk factors, pathogenesis, and current clinical treatments of AMD are briefly introduced. Next, the development status of long-term drug delivery systems is discussed, and the drawbacks and shortages of these systems are emphasized. By comprehensively considering the pathological aspect and the recent application of drug delivery systems in AMD therapy, we hope to find a better solution for the further development of long-term therapeutic strategies for AMD.

show abstract

Section: Clinical Trials Of Therapies For Nvamdmentioning

confidence: 99%

Rethinking the potential and necessity of drug delivery systems in neovascular age-related macular degeneration therapy

Huang

Zhang

et al. 2023

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…A phase 1 multi-center dose escalation trial NCT03452527 evaluated intravitreal injection of ICON-1 in patients with CNV due to nAMD. Primary endpoints of safety and tolerability were met with no reported serious side effects [ 107 ]. EMERGE-2 is a phase 2 trial in which patients were randomized to receive either 0.5 mg ranibizumab and 0.3 mg of ICON-1, 0.5 mg of ranibizumab only, or 0.3 mg of ICON-1 only.…”

Section: Icon-1mentioning

confidence: 99%

Current and Novel Therapeutic Approaches for Treatment of Neovascular Age-Related Macular Degeneration

2022

View full text Add to dashboard Cite

Age-related macular degeneration AMD is one of the leading causes of blindness in the elderly population. An advanced form of AMD known as neovascular AMD (nAMD) is implicated as the main attributor of visual loss among these patients. The hallmark feature of nAMD is the presence of neovascular structures known as choroidal neovascular membranes (CNVs), along with fluid exudation, hemorrhages, and subretinal fibrosis. These pathological changes eventually result in anatomical and visual loss. A type of proangiogenic factor known as vascular endothelial growth factor (VEGF) has been known to mediate the pathological process behind nAMD. Therefore, therapy has transitioned over the years from laser therapy that ablates the lesions to using Anti-VEGF to target the pathology directly. In this work, we provide an overview of current and emerging therapies for the treatment of nAMD. Currently approved Anti-VEGF agents include ranibizumab, aflibercept, and brolucizumab. Bevacizumab, also an Anti-VEGF agent, is used to manage nAMD even though this is an off-label use. While Anti-VEGF agents have provided a favorable prognosis for nAMD, they are associated with a substantial financial burden for patients and the healthcare system, due to their high cost as well as the need for frequent repeat treatments and visits. Emerging therapies and studies aim to extend the intervals between required treatments and introduce new treatment modalities that would improve patients’ compliance and provide superior results.

show abstract

“…Additionally, this therapy can be used in combination with other anti-VEGF medications. ICON-1 has been evaluated in a phase I, open-label trial in 18 patients with neovascular AMD, and met the primary endpoints of safety [ 57 ]. Further investigation of ICON-1 have been undertaken with EMERGE, a phase II, randomized, double-masked study in 88 patients with CNV in neovascular AMD.…”

Section: Drugs In the Pipelinementioning

confidence: 99%

Pipeline therapies for neovascular age related macular degeneration

Arepalli

Kaiser

2021

Int J Retin Vitr

View full text Add to dashboard Cite

Age related macular degeneration (AMD) is the most common cause of vision loss in the elderly population. Neovascular AMD comprises 10% of all cases and can lead to devastating visual loss due to choroidal neovascularization (CNV). There are various cytokine pathways involved in the formation and leakage from CNV. Prior treatments have included focal laser therapy, verteporfin (Visudyne, Bausch and Lomb, Rochester, New York) ocular photodynamic therapy, transpupillary thermotherapy, intravitreal steroids and surgical excision of choroidal neovascular membranes. Currently, the major therapies in AMD focus on the VEGF-A pathway, of which the most common are bevacizumab (Avastin; Genentech, San Francisco, California), ranibizumab (Lucentis; Genentech, South San Francisco, California), and aflibercept (Eylea; Regeneron, Tarrytown, New York). Anti-VEGF agents have revolutionized our treatment of wet AMD; however, real world studies have shown limited visual improvement in patients over time, largely due to the large treatment burden. Cheaper alternatives, including ranibizumab biosimilars, include razumab (Intas Pharmaceuticals Ltd., Ahmedabad, India), FYB 201 (Formycon AG, Munich, Germany and Bioeq Gmbh Holzkirchen, Germany), SB-11 (Samsung Bioepsis, Incheon, South Korea), xlucane (Xbrane Biopharma, Solna, Sweden), PF582 (Pfnex, San Diego, California), CHS3551 (Coherus BioSciences, Redwood City, California). Additionally, aflibercept biosimilars under development include FYB203 (Formycon AG, Munich, Germany and Bioeq Gmbh Holzkirchen, Germany), ALT-L9 (Alteogen, Deajeon, South Korea), MYL1710 (Momenta Pharamaceuticals, Cambridge, MA, and Mylan Pharmacueticals, Canonsburg, PA), CHS-2020 (Coherus BioSciences, Redwood City, California). Those in the pipeline of VEGF targets include abicipar pegol (Abicipar; Allergan, Coolock, Dublin), OPT-302 (Opthea; OPTHEA limited; Victoria, Melbourne), conbercept (Lumitin; Chengdu Kanghong Pharmaceutical Group, Chengdu, Sichuan), and KSI-301 (Kodiak Sciences, Palo Alto, CA). There are also combination medications, which target VEGF and PDGF, VEGF and tissue factor, VEGF and Tie-2, which this paper will also discuss in depth. Furthermore, long lasting depots, such as the ranibizumab port delivery system (PDS) (Genentech, San Francisco, CA), as well as others are under evaluation. Gene therapy present possible longer treatments options as well and are reviewed here. This paper will highlight the past approved medications as well as pipeline therapies for neovascular AMD.

show abstract

A Phase 1, Open-Label, Dose-Escalation Trial to Investigate Safety and Tolerability of Single Intravitreous Injections of ICON-1 Targeting Tissue Factor in Wet AMD

Abstract: Intravitreous administration of ICON-1 in single doses up to 300 μg in eyes with neovascular AMD was safe and well-tolerated. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:336-345.].

Cited by 12 publications

References 12 publications

Rethinking the potential and necessity of drug delivery systems in neovascular age-related macular degeneration therapy

Rethinking the potential and necessity of drug delivery systems in neovascular age-related macular degeneration therapy

Current and Novel Therapeutic Approaches for Treatment of Neovascular Age-Related Macular Degeneration

Pipeline therapies for neovascular age related macular degeneration

Contact Info

Product

Resources

About