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

Understanding anti-vascular endothelial growth factor medications: chemical properties, costs, and side effects. (PubMed, J Med Life) - "This narrative review addressed the fact that the pharmacological properties, safety profiles, and cost-effectiveness of the currently marketed anti-VEGF intravitreal agents (i.e. bevacizumab, ranibizumab, aflibercept, brolucizumab, pegaptanib, and recently faricimab) differ and therefore, each of these agents, have their own unique molecular structure, target specificity, duration of action in the eye, and systemic circulation, each of which will affect the dosing intervals and treatment burden as well as the safety and adverse events associated with each drug. While anti-VEGF therapies are highly effective, the outcomes regarding safety, efficacy, and cost depend heavily on the study design and reflect the actual treatment paradigm and continuum of care within the healthcare system. The various attributes of agents should help personalize a patient's treatment approach while also addressing potential challenges related to the safety, efficacy, and longevity of..."

Adverse events • Journal • Review • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Nanopore-Based Profiling of PEGylation in Nucleic Acid Therapeutics. (PubMed, J Am Chem Soc) - "We further assessed pegaptanib PEGylation and stability in a serum background and demonstrated that nanopore sensing resolves PEG moieties of distinct molecular weights within the oligonucleotide conjugates. Single-molecule profiling of polymer-RNA conjugates enables iterative improvements in oligonucleotide design and provides a direct means to assess their stability in complex biological environments, thereby advancing the development of more effective NATs."

Journal

Signals of drug-related retinal artery occlusion: a multi-country retrospective study from a spontaneous reporting system. (PubMed, Front Med (Lausanne)) - "Strong signals, as indicated by the BCPNN algorithm, were observed for mepivacaine, brolucizumab, and pegaptanib. This study characterizes the reporting patterns and signal strength of RAO across multiple drug classes using pharmacovigilance data. These findings provide real-world evidence to enhance clinical awareness and support safer prescribing practices, while emphasizing the need for further validation in controlled studies."

Journal • Retrospective data • Anesthesia • Oncology

Development and validation of a novel ion-pair hydrophilic interaction liquid chromatography method for the separation and quantification of oligonucleotide therapeutics. (PubMed, SLAS Technol) - "This study provides an systematically optimized and validated analytical platform for the quality control of oligonucleotide medicines, particularly showing significant advantages in the separation of key impurities (e.g., n-1 sequences) for long-chain oligonucleotides (20-30 mer), laying a technical foundation for the precise analysis of hydrophilic biopolymers."

Journal

Peep into anti-vascular endothelial growth factor. (PubMed, Indian J Ophthalmol) - "Beginning with the foundational identification of VEGF as the principal driver of ocular neovascularization, the field has evolved from early agents such as pegaptanib and bevacizumab to more potent molecules including ranibizumab, aflibercept, brolucizumab, and faricimab. In India, the landscape is shaped by unique economic and epidemiological factors, including a high burden of diabetic retinopathy and age-related macular degeneration, limited healthcare reimbursement, and the significant role of biosimilar ranibizumab products in expanding access. This article provides a comprehensive overview of the historical development, pharmacology, regulatory milestones, safety considerations, and current clinical use of anti-VEGF agents in the Indian context, with emphasis on strategies to deliver equitable, high quality retinal care across a diverse population."

Journal • Age-related Macular Degeneration • Cardiovascular • Diabetic Macular Edema • Diabetic Retinopathy • Macular Degeneration • Ophthalmology • Retinal Disorders

RNA therapeutics 2.0: Expanding the landscape from mRNA vaccines to splicing modulators and beyond. (PubMed, Biotechnol Adv) - "RNA therapeutics in combination with gene therapy can be used to produce personalized therapeutics, such as n-of-1 medicines, based on immune regulation and control circuits. This Review describes the development of early oligonucleotide drugs to a diversified arsenal of RNA platforms, the major advancements, obstacles and emerging technology that characterize the next stage of RNA-based precision medicine."

Journal • Review • Gene Therapies • Genetic Disorders • Hepatology • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Oncology • ADAR

Evolution of the Onion Ring Sign in Radiation Retinopathy. (PubMed, Cureus) - "His clinical course included multiple intravitreal injections including triamcinolone acetonide, bevacizumab, pegaptanib, ranibizumab, aflibercept 2 and 8 mg, and dexamethasone implant...The present case demonstrates that the onion ring sign may develop in long-standing radiation retinopathy, likely reflecting the cumulative effects of chronic vascular injury and persistent macular edema. The recognition of this OCT feature may aid in understanding the natural history, chronicity, and metabolic burden of retinal vascular disorders."

Journal • Age-related Macular Degeneration • Cardiovascular • Diabetic Retinopathy • Macular Degeneration • Macular Edema • Ophthalmology • Retinal Disorders

Small RNA or oligonucleotide drugs and challenges in evaluating drug-drug interactions. (PubMed, Front Pharmacol) - "Widespread adoption of these strategies has further enabled the application of oligonucleotides as viable drugs and expanded the class of RNA therapeutics, with thirteen antisense oligonucleotides (ASOs) (fomiversen, mipomersen, nusinersen, inotersen, eteplirsen, golodirsen, casimersen, viltolarsen, tofersen, eplontersen, olezarsen, and donidalorsen), seven small interfering RNAs (siRNAs) (patisiran, givosiran, lumasiran, inclisiran, vutrisiran, nedosiran, and fitusiran), and two aptamers (pegaptanib and avacincaptad pegol) that have been approved by the United States Food and Drug Administration (FDA). This article provides an overview of FDA-approved oligonucleotide therapies, emphasizing chemical modifications, molecular targets for mechanistic actions, and available ADME and PK/PD properties, followed by the discussion of critical needs for risk assessment strategies suited for this unique modality that focuses on possible DDIs with concomitant drugs. The latter may..."

Journal • Review

Cost-Effectiveness of Vascular Endothelial Growth Factor Inhibitors in the Management of Wet Age-Related Macular Degeneration: A Systematic Review. (PubMed, Value Health Reg Issues) - "Decision making in wAMD treatment requires more thorough economic evaluations that incorporate standardized methodologies and lengthy cost assessments."

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

Conbercept Treatment for Heart-Shaped Vascular Intertwined Nets in Macular Neovascularization: Anti-VEGF Drug Therapy Strategy Based on Vascular Geometry Diagnosed by OCTA. (PubMed, Clin Case Rep) - "Anti-VEGF therapies, such as Aflibercept (Eylea), Bevacizumab (Avastin), Brolucizumab (Beovu), Conbercept (Lumitin), Faricimab (Vabysmo), Ranibizumab (Lucentis), and Pegaptanib (Macugen), have significantly transformed MNV management, targeting VEGF to curb this pathological vascular growth. Conbercept, in particular, proved effective against the complex intertwined nets observed in this patient. These findings emphasize the promise of individualized treatment strategies and the potential of OCTA-based vascular geometry classification as a tool for precision medicine."

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

Two-step target recognition for the competitive inhibition activity of an anti-VEGF aptamer. (PubMed, RNA) - "Meanwhile, the tight-complex formation was essential for t44.27 to exert a competitive inhibition of heparin binding to VEGF HBD. These results provide structural insight into how the RNA aptamer specifically interacts with its target molecule to inhibit its activity."

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

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