Izervay (avacincaptad pegol intravitreal solution) / Astellas - LARVOL DELTA

A Study to Learn How Avacincaptad Pegol (Izervay™) is Used in Clinical Practice in People Who Have Geographic Atrophy (clinicaltrials.gov) - P=N/A | N=489 | Active, not recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Real-world retinal vasculitis events reported with FDA-approved intravitreal anti-VEGF and complement inhibitor agents: an analysis of FAERS data. (PubMed, Retina) - "FAERS reporting identified RVAEs across included intravitreal therapies, but cannot establish incidence, causality, or comparative risk, underscoring the need for vigilant reporting and ongoing post-marketing safety surveillance."

FDA event • Journal • Real-world evidence • Inflammation • Ocular Inflammation • Retinal Vein Occlusion • Vasculitis

Examining Real-World Attrition Among Patients Undergoing Complement Inhibitor Intravitreal Therapy for Geographic Atrophy. (PubMed, J Vitreoretin Dis) - "To identify characteristics of patients with geographic atrophy (GA) who received pegcetacoplan or avacincaptad pegol and discontinued treatment...nAMD treatment intervals of more than 6 weeks (OR, 0.59; 95% CI, 0.39-0.90; P = .014) and GA treatment intervals of 6 to 8 weeks (OR, 0.56; 95% CI, 0.43-0.74; P < .001) contributed to decreased odds of attrition. Poor baseline vision and development of new nAMD are associated with patient attrition, and the combination of nAMD and GA and treatment burden challenges patient retention."

Journal • Real-world evidence • Age-related Macular Degeneration • Diabetic Retinopathy • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Pharmaceutical Applications of Nucleic Acid Aptamers: Recent Advances and Future Perspectives in Therapeutics, Biosensing, Bioanalysis, and Process Analysis. (PubMed, Chem Pharm Bull (Tokyo)) - "In therapeutics, the U.S. Food and Drug Administration (FDA) approval of Izervay (avacincaptad pegol) in 2023 marked a significant milestone, renewing interest in aptamer-based drug development...In process analytical technology, aptamers are being applied to real-time monitoring of cell culture conditions and quality control of antibody drug manufacturing. These advances position nucleic acid aptamers as increasingly important tools in pharmaceutical sciences."

IO biomarker • Journal • Review • CNS Disorders • Infectious Disease • Oncology

Real-World Safety of Intravitreal Complement Inhibitor Avacincaptad Pegol for Geographic Atrophy. (PubMed, J Vitreoretin Dis) - "Persistent ocular hypertension occurred in 8 eyes (1.0%), with no ischemic optic neuropathy or retinal vasculitis observed. In this real-world cohort, a favorable safety profile was found with avacincaptad pegol, with low rates of inflammatory events, endophthalmitis, persistent ocular hypertension, and nAMD conversion, providing clinically relevant data to inform patient counseling and monitoring."

Journal • Real-world evidence • Age-related Macular Degeneration • Cardiovascular • Dry Age-related Macular Degeneration • Glaucoma • Inflammation • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • Retinal Disorders • Vasculitis • Wet Age-related Macular Degeneration

Incomplete Retinal Pigment Epithelium and Outer Retinal Atrophy Characterized Using Fundus Autofluorescence: An 18-Month Post Hoc Analysis of GATHER2. (PubMed, Invest Ophthalmol Vis Sci) - P3 | "In this GATHER2 (NCT04435366) post hoc analysis, pooled eyes from participants assigned to avacincaptad pegol (2 mg) or sham were analyzed for baseline iRORA beyond the borders of geographic atrophy; each iRORA was assessed for progression to cRORA at months 6, 12, and 18 using OCT...iRORA that progressed to cRORA by month 18 was more likely to have more advanced FAF abnormalities, with 44.4% having IAF, 30.2% QDAF, and 27.3% DDAF. Findings from this large study reporting FAF characteristics of iRORA highlight the heterogeneity of these lesions and the association of the multimodal phenotype on progression over time."

Clinical • Journal • Retrospective data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration

Comparative Endophthalmitis Rates of Anti-VEGF, Corticosteroid Implants and Anti-Complement Injections: An IRIS® Registry Analysis. (PubMed, Am J Ophthalmol) - "The incidence of post-injection endophthalmitis is greater with corticosteroid implants and anticomplement therapies. Heightened aseptic vigilance may be warranted with injections that necessitate larger gauge needles, modulate the immune response and/or are prepared from a vial."

Journal • Ocular Infections • Ocular Inflammation • Ophthalmology • Pediatrics

A Study About the Safety of ASP3021 Eye Injections and if They Help People in Japan With Vision Loss From Age-related Macular Degeneration (clinicaltrials.gov) - P4 | N=17 | Active, not recruiting | Sponsor: Astellas Pharma Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Avacincaptad Pegol Slows Progressive Ellipsoid Zone Degradation/Loss in Eyes With Geographic Atrophy. (PubMed, Ophthalmology) - "Greater baseline total and partial EZ attenuation were associated with higher rates of GA lesion growth and progressive EZ loss over time, establishing these EZ measures as important predictors of future GA growth and photoreceptor loss. Treatment with ACP reduced EZ loss and degradation over 12 months vs sham. EZ measures may enhance identification of patients at high risk of disease progression who would benefit from early therapeutic intervention."

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

Complement Inhibition in Geographic Atrophy: Clinical Evidence for Pegcetacoplan and Avacincaptad Pegol. (PubMed, Cureus) - "Despite favorable structural outcomes, functional endpoints like best-corrected visual acuity (BCVA) and low-luminance visual acuity (LLVA) have shown limited improvement, and concerns remain regarding their side effect profile. This narrative review provides an overview of GA, emphasizing its pathophysiology and the role of the complement cascade, and discusses the clinical relevance of complement inhibitors in the current management of the disease."

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

A Study to Learn How Avacincaptad Pegol (Izervay™) is Used in Clinical Practice in People Who Have Geographic Atrophy (clinicaltrials.gov) - P=N/A | N=500 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | N=1000 ➔ 500 | Trial completion date: Jan 2030 ➔ Oct 2030 | Trial primary completion date: Jan 2030 ➔ Oct 2030

Enrollment change • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Geographic atrophy: From slowing lesions to preserving vision. (PubMed, Curr Opin Ophthalmol) - "Structural slowing alone does not fully capture therapeutic value in geographic atrophy. Functional measures provide a more sensitive and patient-centered assessment of disease progression and treatment impact."

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

Real-world outcomes of patients with geographic atrophy developing neovascular age-related macular degeneration after receiving anti-complement therapy (ARVO 2026) - "Purpose Geographic atrophy (GA) treatments targeting complement inhibition, pegcetacoplan and avacincaptad pegol, have demonstrated efficacy in reducing GA lesion size growth but have also been associated with higher rates of conversion to neovascular age-related macular degeneration (nAMD) in clinical trials...We found that patients who received complement-inhibiting injections were more likely to develop nAMD, especially with increasing numbers of injections. These results highlight the importance of careful monitoring for patients receiving GA treatment."

Clinical • Real-world • Real-world evidence • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Two Year Real-World Practice Patterns, Outcomes, and Adverse Events for Pegcetacoplan and Avacincaptad Pegol for Geographic Atrophy: An Analysis of the Retina Consultants of America Database (ARVO 2026) - "Purpose Geographic Atrophy (GA) is a leading cause of vision loss in age-related macular degeneration, with only 2 FDA-approved therapies: pegcetacoplan (PEG, Syfovre) and avacincaptad pegol (ACP, Izervay). All treated eyes had slow loss of vision across cohorts. PEG and ACP were each associated with 2 cases of NAION, and PEG with 3 cases of ORV."

Adverse events • Clinical • Real-world • Real-world evidence • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders

Avacincaptad Pegol for Geographic Atrophy: 3.5-Year Results From the GATHER2 Open-Label Extension Trial (ARVO 2026) - P3 | "This means people may be able to see for longer. Starting ACP earlier in the disease was better at slowing down the damage."

Clinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders

Comparing adverse event profiles of pegcetacoplan and avacincaptad pegol for treatment of geographic atrophy (ARVO 2026) - "Conclusions We identified greater ROR of adverse events in pegcetacoplan when compared to avacincaptad pegol including inflammatory mediated and hemorrhage side effects. This study helps identify the risk of adverse events when using either medication and provides valuable evidence that can aide in clinical decison making for AMD."

Adverse events • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Population pharmacokinetics profile of avacincaptad pegol, a pegylated RNA aptamer approved for the treatment of GA secondary to AMD (ARVO 2026) - P1, P3 | "Importantly, ACP behaved the same way in the body regardless of once a month or every other month dosing. Overall, ACP worked in a stable and safe way, supporting its use in patients with GA."

Clinical • PK/PD data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Time-to-event analysis of driving eligibility maintenance following treatment with avacincaptad pegol in patients with geographic atrophy (ARVO 2026) - "Also, people who got ACP were more likely to keep driving than those that did not get ACP. That means ACP may be able to protect the ability to see well enough to keep a driver's license for longer."

Clinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Real-World Comparative 2-Monthly Treatment Outcomes of Syfovre and Izervay in Geographic Atrophy: A Multimodal Imaging Biomarker Analysis with External Sham-Arm Contextualization (ARVO 2026) - "Conclusions Real-world 2-monthly Syfovre and Izervay show broadly similar effects on GA enlargement, VA change, and foveal involvement, and both demonstrate slower GA progression than sham benchmarks. Structural OCT biomarkers—particularly EZ loss and foveal status—were the strongest predictors of rapid progression and major VA decline, supporting an anatomy-centered risk framework for GA."

Biomarker • Clinical • Real-world • Real-world evidence • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Anti-C5 therapy for the treament of Geographic Atrophy affects retinal function. (ARVO 2026) - "Methods Light adapted full-field ERG studies were obtained in 10 patients receiving anti C5 therapy with avacincaptad pegol, before and after therapy commenced, using Diopsys NOVA from September 2020 to present...Our data shows an increase in photoreceptor amplitudes with a decrease in bipolar cell function over time in patients with GA, that is accelerated with anti-C5 therapy. This is an important consideration in patients receiving long-term therapy for this condition."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Long-Term Impact of Higher-Volume Intravitreal Injections on Intraocular Pressure and Glaucoma Outcomes (ARVO 2026) - "Methods Eyes diagnosed with nAMD, GA, or diabetic macular edema between 01-01-2015 and 08-31-2025 and treated with aflibercept 8 mg (AFL8), pegcetacoplan (PEG), or avacincaptad pegol (ACP) were accrued from a de-identified database of patients seen by American private practice retina specialists...Conclusions This matched cohort study isolated the volumetric influence of intravitreal injections on long-term IOP and glaucoma/OHTN outcomes. Compared to controls, treatment with higher-volume injections was not associated with an increased risk of developing >5 mmHg or ≥25 mmHg IOP elevations, glaucoma/OHTN, or requiring new pressure control drops."

Diabetic Macular Edema • Glaucoma • Ophthalmology

Evaluation of Inter-grader Reproducibility of Geographic Atrophy Grading Using Infrared Optical Coherence Tomography and Fundus Autofluorescence Images (ARVO 2026) - "Methods A retrospective review was conducted of patients with advanced AMD receiving intravitreal Avacincaptad pegol at the Duke Eye Center since 2023...Conclusions Inter-grader reproducibility was excellent for both IR-OCT and FAF modalities. GA area measured on NIR-OCT closely matched FAF, supporting the use of NIR-OCT for GA assessment in routine clinical care."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Avacincaptad Pegol for Geographic Atrophy: Pharmacokinetics and Immunogenicity From the GATHER2 Open-Label Extension (ARVO 2026) - P3 | "Activating the immune system did not change ACP levels in the blood. Results show that ACP can be used long term at levels that keep ACP working and that do not cause serious side effects."

Clinical • PK/PD data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Real-world rates of neovascular age-related macular degeneration in eyes treated with pegcetacoplan or avacincaptad pegol for geographic atrophy (ARVO 2026) - "In this study, the percentage converting to nAMD was higher for pegcetacoplan than ACP, although this interpretation should be tempered by the substantially larger sample of pegcetacoplan-treated eyes. Further investigation with a larger sample size and detailed historical baseline optical coherence tomography (OCT) image analysis will be necessary for more conclusive results."

Clinical • Real-world • Real-world evidence • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Predictors of Attrition among Patients Receiving Complement Inhibitor Intravitreal Therapy for Geographic Atrophy (ARVO 2026) - "Purpose We performed two retrospective cohort studies using a large geographically and demographically diverse database to identify baseline and follow-up characteristics of patients with geographic atrophy (GA) receiving pegcetacoplan (PEG) or avacincaptad pegol (ACP), who discontinue treatment...Even after starting GA treatment, poor baseline VA increases the odds of discontinuation. Additionally, losses in VA and the burden of nAMD and GA treatments contribute to GA treatment discontinuation."

Clinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders