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

Real-world Safety Profile of Avacincaptad Pegol in the Management of Geographic Atrophy. (PubMed, Ophthalmic Surg Lasers Imaging Retina) - "Five patients discontinued treatment, and one eye (0.8%) had reactivation of neovascular AMD. Our study highlights the safety profile of avacincaptad pegol for GA, with a low incidence of conversion to neovascular AMD, few adverse events, and manageable side effects."

Journal • Real-world evidence • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Hematological Disorders • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Novel drug development for geographic atrophy. (PubMed, Asia Pac J Ophthalmol (Phila)) - "A marked important therapeutic milestone with the first FDA approvals of complement inhibitors, Pegcetacoplan and Avacincaptad pegol, demonstrated a modest but statistically significant slowing of lesion growth...Key challenges include treatment burden associated with frequent intravitreal injections, safety considerations, and the persistent disconnect between anatomic endpoints and functional outcomes. These underscore the necessity for future treatments that not only alter disease anatomy but also effectively preserve patients' vision and improve their quality of life."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Inflammation • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders

Safety and tolerability of avacincaptad pegol in combination with ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration: results from a phase 1 and phase 2a study. (PubMed, BMJ Open Ophthalmol) - P1, P2 | "Coadministration of ACP and ranibizumab in treatment-naïve patients with nAMD was well tolerated across different dosing regimens with no new safety issues based on results from two independent studies."

Clinical • Journal • P1 data • P2a data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Ophthalmology : what's new in 2025 (PubMed, Rev Med Suisse) - "Presbyopia, atrophic age-related macular degeneration, and thyroid eye disease are ophthalmic conditions that can significantly affect patients' vision and quality of life. In this article, we present the most recent therapeutic innovations for their management, including the myotic eye drop aceclidine for presbyopia, complement inhibitors (pegcetacoplan, avacincaptad pegol) to slow the progression of atrophic AMD, and teprotumumab, an anti-IGF1-R antibody, to reduce proptosis and diplopia in thyroid eye disease."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Thyroid Eye Disease • IGF1

Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies. (PubMed, Int J Mol Sci) - "Although the recent U.S. Food and Drug Administration (FDA) approvals of pegcetacoplan and avacincaptad pegol represent major milestones, their therapeutic effects remain modest...Finally, we review current and emerging therapeutic strategies-including complement inhibitors, visual cycle modulators, and mitochondrial-protective approaches-and outline future directions for translational research. Collectively, this review synthesizes mechanistic insights, disease models, and therapeutic innovation to support the development of targeted and stage-specific interventions for dry AMD."

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

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

Comparative Efficacy and Safety of Avacincaptad Pegol vs. Pegcetacoplan in Treatment of Geographic Atrophy: Insights From a Multilevel Network Meta-Regression (ISPOR-EU 2025) - "ACP was associated with a significantly lower incidence of new onset CNV compared to PEG while maintaining similar efficacy in slowing GA lesion growth and visual acuity loss. The key strength of this analysis is the use of ML-NMR, which leverages all available data to achieve robust population adjustment across all EMs identified through published evidence and/or clinical opinion. These insights help address a critical evidence gap in the evolving treatment paradigm for GA."

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

Study to Evaluate Efficacy and Safety of ONL1204 in Patients With GA Associated With AMD (clinicaltrials.gov) - P2 | N=324 | Recruiting | Sponsor: ONL Therapeutics | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2027 ➔ Nov 2028 | Trial primary completion date: Nov 2027 ➔ Nov 2028

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

Efficacy of Intravitreal Pegcetacoplan vs Avacincaptad Pegol in Patients With Geographic Atrophy. (PubMed, J Vitreoretin Dis) - P3 | "A numerically greater reduction in GA lesion growth was observed with pegcetacoplan every other month vs avacincaptad pegol monthly (95% CI, -1.130 to -0.300; P = .25). Matching-adjusted indirect comparisons support a greater reduction in GA growth with pegcetacoplan monthly vs avacincaptad pegol monthly and no significant difference between pegcetacoplan every other month and avacincaptad pegol monthly."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration

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=20 | Recruiting | Sponsor: Astellas Pharma Inc | Phase classification: P3 ➔ P4

Phase classification • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Astellas to Present New Data on IZERVAY (avacincaptad pegol intravitreal solution) in Geographic Atrophy at AAO 2025 Annual Meeting (PRNewswire) - "The data feature long-term safety and efficacy results from the GATHER2 open-label extension study, real-world evidence on treatment patterns and safety of IZERVAY in the U.S., and the latest findings on a structure-function link in GA via ellipsoid zone integrity and low-luminance deficit."

P3 data • Age-related Macular Degeneration

Astellas Pharma…announced that the Japanese Ministry of Health, Labor and Welfare (MHLW) has granted Conditional Approval of IZERVAY (avacincaptad pegol intravitreal solution: ACP) for the suppression of geographic atrophy (GA) growth in atrophic age-related macular degeneration (AMD) (Astellas Press Release) - "In the global GATHER1 and GATHER2 clinical trials, ACP met its primary endpoint by significantly reducing the rate of GA lesion growth compared with sham."

Japan approval • Age-related Macular Degeneration

Real-World Experience of Geographic Atrophy Treatment With Avacincaptad Pegol. (PubMed, J Vitreoretin Dis) - "One eye (0.2%) developed a vitreous hemorrhage. This study describes the real-world safety profile of avacincaptad pegol that may aid clinicians in understanding the risk of adverse events associated with this relatively new treatment for GA."

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

Financial Results of Astellas for the First Three Months of FY2025 (Astellas Press Release) - "Sales of PADCEV for the treatment of urothelial cancer, IZERVAY for the treatment for geographic atrophy secondary to age-related macular degeneration, VEOZAH for the treatment of vasomotor symptoms due to menopause and XTANDI for the treatment of prostate cancer showed solid growth. - Furthermore, sales of VYLOY for the treatment of gastric and gastroesophageal junction adenocarcinoma which was launched in the previous fiscal year contributed to increased revenue. As a result of the above, revenue in the first three months of FY2025 increased by 6.9% compared to that in the previous fiscal year (“year-on-year”) to ¥505.8 billion"

Commercial • Age-related Macular Degeneration • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Prostate Cancer • Urothelial Cancer

Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy. (PubMed, Int J Mol Sci) - "Recently, marketing authorizations were granted by the Federal Drug Administration (FDA) for pegcetacoplan and avacincaptad pegol, which inhibit C3 and C5 complement components, respectively...Tecfidera®, whose active principle is dimethyl fumarate, is already commercialized for the treatment of autoimmune diseases such as multiple sclerosis and psoriasis. The aim of this review is to present the rationale and the design of the clinical trial we initiated to test the effectiveness and safety of repurposing Tecfidera®, which could represent a new therapeutic alternative in patients with the dry form of AMD."

Journal • Review • Age-related Macular Degeneration • CNS Disorders • Dermatology • Dry Age-related Macular Degeneration • Immunology • Inflammation • Macular Degeneration • Multiple Sclerosis • Ophthalmology • Psoriasis • Retinal Disorders

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) - P3 | N=20 | Recruiting | Sponsor: Astellas Pharma Inc | Not yet recruiting ➔ Recruiting

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

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

Zimura Compared to Sham in Patients With Autosomal Recessive Stargardt Disease (STGD1) (clinicaltrials.gov) - P2 | N=121 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Active, not recruiting ➔ Completed

Trial completion • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study to Investigate Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD), and Immunogenicity of RO7669330 in Participants With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P1 | N=132 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

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

Silicone oil microdroplets from syringes with intravitreal anti-vascular endothelial growth factor and complement inhibitor injections. (PubMed, Retina) - "Commonly used BD polycarbonate syringes for intravitreal injections caused significantly higher levels of silicone oil to be injected into the eye than prefilled or silicone free syringes. Repeated injections with more viscous intravitreal drugs increase the amount of silicone oil in the vitreous, leading to symptomatic floaters."

Journal

A Study to Investigate Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD), and Immunogenicity of RO7669330 in Participants With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD) (clinicaltrials.gov) - P1 | N=132 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1 trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Avacincaptad Pegol Open-Label Extension for Patients With Geographic Atrophy (clinicaltrials.gov) - P3 | N=278 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Active, not recruiting ➔ Completed

Trial completion • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Innovative technologies for the treatment of dry age-related macular degeneration (AMD) - modern therapeutic perspectives and their future. (PubMed, Rom J Ophthalmol) - "Advances include molecularly targeted therapies (Pegcetacoplan, Avacincaptad Pegol) that reduce inflammation, gene therapy (HMR59) protecting RPE cells, and mitochondria-targeted drugs (SS-31) mitigating oxidative stress...However, further clinical trials are needed to optimize these strategies, assess long-term outcomes, and expand patient access to effective treatments. These advancements have the potential to significantly improve the quality of life for individuals affected by dry AMD."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Infectious Disease • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Transplantation

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) - P3 | N=20 | Not yet recruiting | Sponsor: Astellas Pharma Inc

New P3 trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Astellas to Present New Data in Geographic Atrophy at Upcoming Ophthalmology Annual Congresses (PRNewswire) - "Research highlights include: An oral presentation on the structure-function relationship between baseline central subfield ellipsoid zone (EZ) integrity and visual acuity at baseline and future vision loss; An oral presentation on baseline EZ integrity features linked to GA progression in eyes with differential shifts in GA growth rate; Multiple posters evaluating imaging data from the GATHER1 and GATHER2 studies, which link structure and function in GA; Two preclinical posters with structural insights refining the mechanism of action, as well as pharmacokinetics and pharmacodynamics, of avacincaptad pegol (ACP); Data from qualitative studies assessing the experience of patients with GA in the U.S., Spain, Germany and France, including the impact of disease symptoms on health-related quality of life (HRQoL) and coping mechanisms used to manage symptoms of GA."

Clinical data • Preclinical • Age-related Macular Degeneration • Ophthalmology