Macugen (pegaptanib) / Bausch Health, Gilead, Pfizer - LARVOL DELTA

Aptamers as therapeutic targets: prospects and progress in the treatment of cancers. (PubMed, Nucleosides Nucleotides Nucleic Acids) - "Pegaptanib and Izervay are the approved aptamers against age-related macular degeneration (AMD) that target vascular endothelial growth factor (VEGF) and block complement component protein C5, respectively...Aptamosomes, encapsulating drugs like doxorubicin, effectively reduce tumour size and are highly advantageous over targeted drug delivery...It also outlines the roles of aptamers and connects their modes of action with specific cancer types. The content is highly detailed, providing a comprehensive understanding of aptamer therapy and its applications."

Journal • Review • Age-related Macular Degeneration • Hematological Malignancies • Leukemia • Macular Degeneration • Oncology • Ophthalmology • Retinal Disorders • AXL • EGFR • MUC1 • SPP1 • VIM

Multifaceted arsenal in SELEX nanomedicine. (PubMed, Adv Colloid Interface Sci) - "This review explores SELEX-derived aptamers in nanomedicine, focusing on their therapeutic and diagnostic roles, particularly in precision cancer therapies. It also addresses challenges such as degradation and clinical translation alongside prospects in vaccines, tissue engineering, and regenerative medicine."

Journal • Review • Diabetes • Immunology • Metabolic Disorders • Oncology

The 20th Anniversary of Pegaptanib (MacugenTM), the First Approved Aptamer Medicine: History, Recent Advances and Future Prospects of Aptamers in Therapy. (PubMed, Pharmaceutics) - "Despite their high potential, only two aptamers have been approved to date, pegaptanib (MacugenTM) and avacincaptad pegol (IzervayTM), both for the treatment of age-related macular degeneration (AMD). We describe its chemistry and track its development from the earliest stages to the preclinical phase, clinical trials, and eventual regulatory approval. Additionally, we evaluate its position among other therapeutic agents and provide a comprehensive overview of pegaptanib's efficacy, safety, and cost-effectiveness, comparing these aspects with those of monoclonal antibodies with similar indications, bevacizumab and ranibizumab."

Journal • Review • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

LYMPHOCYTE, NK CELL AND MITOCHONDRIAL GENE DYSREGULATION PATTERNS SEPARATE PATIENTS WITH NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS INTO DISTINCT SUBGROUPS WITH DIFFERENTIAL ANTICIPATED RESPONSE TO TARGETED THERAPIES (EULAR 2024) - "Drugs annotated to the cytotoxic/NK cell network included pegaptanib, a selective vascular endothelial growth factor (VEGF) antagonist, while many anticonvulsants such as zonisamide, lamotrigine, and oxcarbazepine showed potential for counteracting the transcriptomic signature associated with the B cell module. Druggability analysis for the mitochondrial cluster module revealed potential for the centrally acting angiotensin-converting enzyme inhibitor captopril, the mammalian target of rapamycin (mTOR) inhibitor everolimus, the proteasome inhibitor bortezomib, the toll-like receptor 5 (TLR5) agonist entolimod, and the spleen tyrosine kinase (SYK) inhibitor fostamatinib. In silico prediction algorithms demonstrated a greater anticipated response to anifrolumab and calcineurin inhibitors for the active CNS subgroup with B cell, T cell, cytotoxic/NK cell, and mitochondrial gene downregulation compared with the patient subgroup of mixed dysregulation patterns. In this..."

Clinical • IO biomarker • Immunology • Inflammatory Arthritis • Lupus • Metabolic Disorders • Psychiatry • Systemic Lupus Erythematosus • SYK

Exploring the Therapeutic Potential of Anti-VEGF Drugs for the Management of Diabetic Retinopathy: An Overview. (PubMed, Curr Diabetes Rev) - "Over the past decade, drugs that impede the functions of vascular endothelial growth factors have established themselves as a standard-of-care treatment for a range of ocular ailments and improved patients' clinical results with diabetic retinopathy and Diabetic Macular Edema, and their frequency has grown exponentially with the introduction of these agents Pegaptanib, Ranibizumab, and Aflibercept which are approved for ophthalmic indications, while Bevacizumab is used off-label. However, issues with compounding, counterfeiting, and off-label usage restrict its availability in many nations. The pharmacology, pharmacokinetics, pharmacodynamics, adverse effects, and contraindications of antivascular endothelial growth factor agents are discussed, and the results of clinical trials evaluating their efficacy are summarized."

Journal • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Retinal Disorders

A Comprehensive Analysis of NRP1 in Malignancies Provide Therapeutic Implication for Treating Cancer Patients Infected with SARS-CoV-2. (PubMed, Biochem Genet) - "Overall, NRP1 appears to play a critical role in regulating immunological properties and metabolism in many tumor types. Specific inhibitors of the NRP1 antigen (pegaptanib, EG00229, or MNRP1685A) combined with other anti-SARS-CoV-2 strategies may aid in treating patients with lung and genitourinary cancers following SARS-CoV-2 infection."

Journal • Genito-urinary Cancer • Infectious Disease • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • NRP1

A real-world disproportionality analysis of anti-VEGF drugs from the FDA Adverse Event Reporting System. (PubMed, Expert Opin Drug Saf) - "A disproportionality analysis of reports from the FDA Adverse Event Reporting System from January 2004 to September 2021 was conducted to detect the significant ADR signals with anti-VEGF drugs (including aflibercept, bevacizumab, brolucizumab, pegaptanib, and ranibizumab). Our findings support the associations between anti-VEGF drugs and ocular AEs, cardiac AEs, and central nervous AEs. After intravitreal injection, attention should not only be paid to ocular symptoms, but also to systemic symptoms."

Adverse events • Journal • Real-world • Real-world evidence • Cardiovascular • Ophthalmology

Discovery of Aptamers and the Acceleration of the Development of Targeting Research in Ophthalmology. (PubMed, Int J Nanomedicine) - "Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders."

Journal • Review • Age-related Macular Degeneration • Diabetic Retinopathy • Eye Cancer • Fibrosis • Glaucoma • Immunology • Macular Degeneration • Ocular Melanoma • Oncology • Ophthalmology • Retinal Disorders • CTGF • NCL • TFRC • TGFB1

The population affected by neovascular age-related macular degeneration and treated with anti-Vegf through Italian administrative healthcare data. (PubMed, Recenti Prog Med) - "This analysis suggests that in Italy people with nAmd and new users of anti-Vegf are elderly, affected by many comorbidities, treated with Ivt anti-VEGF less than what is required and authorized to achieve a benefit, undergo very few follow-up outpatient specialist visits and tests and, within the 2nd year, their hospitalizations for causes different from nAmd mainly weighs on the total expenditure charged to the Inhs."

Journal • Age-related Macular Degeneration • Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis. (PubMed, JMIR Res Protoc) - "This review will provide a synthesis of current information and underlying evidence about the off-label use of bevacizumab in neovascular AMD. It will provide a clearer vision of a possible new pharmacological approach, as well as the most suitable treatment designs, for the treatment of neovascular AMD."

Clinical • Journal • Retrospective data • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Modern trends in anti-VEGF therapy for age-related macular degeneration (PubMed, Vestn Oftalmol) - "Subsequently, a molecule with a similar mechanism of action was developed and named ranibizumab, which is a humanized monoclonal Fab fragment; it was specifically designed for ophthalmology...Aflibercept and conbercept are recombinant fusion proteins that act as soluble decoy receptors for VEGF family proteins...Simultaneously with studying brolucizumab, another study was conducted involving Abicipar pegol, but that drug showed a high rate of complications. The latest drug registered for the treatment of neovascular AMD is faricimab. The molecule of this drug is a humanized immunoglobulin G antibody that acts on two key points of angiogenesis: VEGF-A and angiopoietin-2 (Ang-2). Thus, the strategy for advancing anti-VEGF therapy lies in the development of molecules with greater efficiency (better effect on newly formed vessels leading to resorption of exudate in the retina, under the neuroepithelium and under the retinal pigment epithelium), which allows not just to..."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Targeting angiogenesis in oncology, ophthalmology and beyond. (PubMed, Nat Rev Drug Discov) - "The concept of targeting angiogenesis for treating diseases was proposed more than 50 years ago, and the first two drugs targeting vascular endothelial growth factor (VEGF), bevacizumab and pegaptanib, were approved in 2004 for the treatment of cancer and neovascular ophthalmic diseases, respectively. However, there is a need to improve clinical outcomes by enhancing therapeutic efficacy, overcoming drug resistance, defining surrogate markers, combining with other drugs and developing the next generation of therapeutics. In this Review, we examine emerging new targets, the development of new drugs and challenging issues such as the mode of action of AADs and elucidating mechanisms underlying clinical benefits; we also discuss possible future directions of the field."

Journal • Review • Oncology • Ophthalmology

Anti-vascular endothelial growth factor for proliferative diabetic retinopathy. (PubMed, Cochrane Database Syst Rev) - "Anti-VEGFs ± PRP compared with PRP alone probably increase visual acuity, but the degree of improvement is not clinically meaningful. Regarding secondary outcomes, anti-VEGFs ± PRP produce a regression of new vessels, reduce vitreous haemorrhage, and may reduce the need for vitrectomy compared with eyes that received PRP alone. We do not know if anti-VEGFs ± PRP have an impact on the incidence of adverse events and they may have little or no effect on patients' quality of life. Carefully designed and conducted clinical trials are required, assessing the optimal schedule of anti-VEGFs alone compared with PRP, and with a longer follow-up."

Journal • Review • Diabetic Retinopathy • Ophthalmology • Retinal Disorders

Molecular mechanism of binding between a therapeutic RNA aptamer and its protein target VEGF: A molecular dynamics study. (PubMed, J Comput Chem) - "The mechanism of the molecular recognition between HBD and Macugen is investigated here using all-atom molecular dynamics simulations. We find that Macugen recognizes HBD by an induced-fit mechanism with major conformational changes in Macugen and almost no changes in the structure of HBD, whereas HBD recognizes Macugen by a conformational selection mechanism."

Journal • VEGFA

Recent trends in anti-vascular endothelial growth factor intravitreal injections: a large claims database study in Japan. (PubMed, Jpn J Ophthalmol) - "These findings can be used as a benchmark for the clinical practice of anti-VEGF therapy."

Journal • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

Comparison of adverse events between intravitreal anti-VEGF and laser photocoagulation for treatment-requiring retinopathy of prematurity: a systematic review. (PubMed, Int Ophthalmol) - "There is need for future primary studies assessing the adverse events of intravitreal anti-VEGF injections compared with LPC as treatment modalities for infants with TR-ROP."

Adverse events • Clinical • Journal • Review • Ophthalmology • Retinal Disorders • Retinopathy of Prematurity

Angiogenic footprints in diabetic retinopathy: opportunities for drug development. (PubMed, Biotechnol Genet Eng Rev) - "4 widely explored drugs being-Bevacizumab, pegaptanib sodium, ranibizumab, and aflibercept. The review article tries to summarize studies illustrating the efficacy of these drugs in the treatment of diabetic retinopathy along with some of the herbal therapeutic paradigms displaying anti-angiogenic action that is being used to treat this condition."

Journal • Diabetes • Diabetic Retinopathy • Glaucoma • Metabolic Disorders • Ophthalmology • Retinal Disorders

Quantitative pharmacokinetic analyses of anterior and posterior elimination routes of intravitreal anti-VEGF macromolecules using published human and rabbit data. (PubMed, Exp Eye Res) - "The purpose of this study was to evaluate the contribution of the anterior elimination route for four anti-vascular endothelial growth factor (anti-VEGF) macromolecules (aflibercept, bevacizumab, pegaptanib and ranibizumab) after intravitreal injection using published human and rabbit data and three previously described pharmacokinetic (PK) modeling methods. The results suggest that the anterior elimination route dominates after intravitreal injection of anti-VEGF macromolecules. However, the clinical data are sparse and variability is extensive, the latter emphasizing the need of proper experimental design."

Journal • PK/PD data • Preclinical

Rapidly dissolving bilayer microneedles enabling minimally invasive and efficient protein delivery to the posterior segment of the eye. (PubMed, Drug Deliv Transl Res) - "The discovery of proteins that neutralise vascular endothelial growth factors, such as pegaptanib, ranibizumab and aflibercept, can inhibit the process of angiogenesis, thereby restoring eyesight in individuals with retinal vascular disorders. Furthermore, ex vivo permeation studies showed that optimised MNs could permeate 86.99 ± 7.37% of OVA through the sclera, twice that of the needle-free patch (42.16 ± 3.95%), highlighting the capability of MNs to circumvent physical barriers and promote protein delivery to the posterior segment of the eye. In this work, a novel, efficient and safe intraocular protein delivery system was successfully established."

Journal • Ophthalmology • Retinal Disorders

Intravitreal Anti-vascular Endothelial Growth Factor Injection for Retinopathy of Prematurity: A Systematic Review and Meta-Analysis. (PubMed, Front Med (Lausanne)) - "We included randomized controlled trials (RCTs) that compared intravitreal anti-VEGF monotherapy (e.g., bevacizumab, ranibizumab, aflibercept, and pegaptanib) with laser photocoagulation in preterm infants with ROP. Pooled analysis revealed no significant difference between the two arms with respect to the recurrence rate, treatment switching, retreatment, and mortality rate, with quality of evidence ranging from moderate to very low as per the GRADE approach. [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42021270077]."

Retrospective data • Review • Retinal Disorders • Retinopathy of Prematurity

Absorption, Distribution, Metabolism, and Excretion of FDA-approved Antisense Oligonucleotide Drugs. (PubMed, FASEB J) - "To better understand their ADME features, ten FDA-approved ASO drugs were selected, including Fomivirsen, Pegaptanib, Nusinersen, Mipomersen, Inotersen, Defibrotide, Eteplirsen, Golodirsen, Viltolarsen, and Casimersen. The summarized information provides the most updated knowledge of ADME characteristics of these ASO drugs, leading to a better understanding of their therapeutic efficacy and potential ADRs and toxicity. Numerous knowledge gaps, particularly on cellular uptake and subcellular trafficking and distributions are identified and future perspective and directions are discussed."

FDA event • Journal

Efficacy and Safety of Antivascular Endothelial Growth Factor (Anti-VEGF) in Treating Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Meta-analysis. (PubMed, J Immunol Res) - "Bevacizumab was linked with less changes in central macular thickness after 1 year compared to control (WMD: -38.50; P < 0.001), but more changes compared to ranibizumab (WMD: 10.69; P = 0.024). Moreover, ranibizumab was associated with more BCVA changes and an increased incidence of gain of 15 or more letter visual acuity after 2 years compared with control (RR: 5.77; P < 0.001). This study found that most anti-VEGF inhibitors provided better efficacy than non-anti-VEGF intervention, and the treatment effectiveness among various anti-VEGF agents was equally effective."

Journal • Retrospective data • Review • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Translation of aptamers toward clinical diagnosis and commercialization. (PubMed, Biosens Bioelectron) - "Macugen® (pegaptanib) was the first aptamer drug approved by the US Food and Drug Administration (FDA), and various aptamer-based diagnostics show great promise in preclinical research and clinical trials. In this review, we introduce recent literature, ongoing clinical trials, commercial reagents of aptamer-based diagnostics, discuss the FDA regulatory mechanisms, and highlight the prospects and challenges in translating these studies into viable clinical diagnostic tools."

Journal • Review

Retrospective Analysis of the Pharmaco-Utilization of VEGF Inhibitors and Health Care Costs among Patients with Wet Age-Related Macular Degeneration and Other Ocular Diseases in Italy. (PubMed, Int J Environ Res Public Health) - "Across January 2010-December 2017, patients aged ≥50 years with a prescription of intravitreal anti-VEGFs were included as "wAMD" patients [by wAMD hospitalization or intravitreal injections] or as "other ocular diseases" patients [by hospitalization for other ocular disorders or intravitreal injections, with concomitant diabetes diagnosis or dexamethasone treatment]...Overall, 2646 patients were enclosed; 85.9% were treated with Ranibizumab, 13.5% with Aflibercept, and 0.6% with Pegaptanib. During the follow-up, the mean/annual anti-VEGF prescription [3.3 (first-year)-0.5 (third-year)] and the total cost [7196.83 € (first-year)-5162.68 € (third-year)] decreased. This observational study highlighted a decline in anti-VEGF prescriptions over time in both cohorts, suggesting a trend of under-treatment that could worsen the patients' clinical outcomes and increase health care resource consumption."

HEOR • Journal • Retrospective data • Age-related Macular Degeneration • Diabetes • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Absorption, distribution, metabolism, and excretion of FDA-approved antisense oligonucleotide drugs. (PubMed, Drug Metab Dispos) - "In this review, to better understand their ADME, the ten FDA-approved ASO drugs were selected, including Fomivirsen, Pegaptanib, Mipomersen, Nusinersen, Inotersen, Defibrotide, Eteplirsen, Golodirsen, Viltolarsen, and Casimersen. Significance Statement Through a systematic analysis of the existing information of ADME parameters for ten FDA-approved ASO drugs, this review provides an overall view of the unique ADME characteristics of ASO drugs, which are distinct from small chemical drug ADME. This knowledge is useful for discovery and development of new ASO drugs as well as clinical use of current FDA-approved ASO drugs."

FDA event • Journal