Syfovre (pegcetacoplan intravitreal) / Apellis - LARVOL DELTA

Complement inhibitor use is not a significant predictor of cancer incidence: A real-world study of patients requiring chronic complement blockade. (ASH 2025) - "Sixwere treated with eculizumab and ravulizumab, 4 with eculizumab alone, 1 with ravulizumab alone, and 1with eculizumab, ravulizumab, pegcetacoplan, and iptacopan at various points...Factors such asfamily history, smoking/alcohol use, and past medical history of HPV, hepatitis B, hepatitis C, and HIVremain established predictors for cancer incidence. Further analysis in a larger cohort is needed tovalidate these initial results."

Clinical • Real-world • Real-world evidence • Age-related Macular Degeneration • Atypical Hemolytic Uremic Syndrome • Bladder Cancer • Breast Cancer • CNS Disorders • Complement-mediated Rare Disorders • Endocrine Cancer • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Kaposi Sarcoma • Macular Degeneration • Myasthenia Gravis • Nephrology • Neuromyelitis Optica Spectrum Disorder • Oncology • Ophthalmology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Retinal Disorders • Sarcoma • Solid Tumor

Effect of Pegcetacoplan on Aqueous Humor Proteome in Geographic Atrophy: A Prospective Exploration. (PubMed, Invest Ophthalmol Vis Sci) - "Although no changes in the target protein C3 were detected following treatment, significant changes in proteins tightly connected to complement, inflammation, and coagulation were observed. These findings underscore the need for further investigation into the biological and clinical relevance of the observed molecular shifts."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • C1QB

Geographic Atrophy Progression in Clinical Practice Before and After Pegcetacoplan Treatment. (PubMed, Vision (Basel)) - "This retrospective study evaluated changes in ocular characteristics and retinal pigment epithelium (RPE) and photoreceptor ellipsoid zone (EZ) depletion rates before and after intravitreal pegcetacoplan initiation in clinical practice...These real-world findings align with data from the pegcetacoplan phase 3 trials, showing reduced RPE and EZ depletion rates without changes in rates of BRVA loss. Additional studies are warranted."

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

Real-World Clinical Usage and Safety Profile of Intravitreal Pegcetacoplan in Age-Related Macular Degeneration-Associated Geographic Atrophy. (PubMed, J Vitreoretin Dis) - "Preserved or improved visual acuity while undergoing anti-VEGF therapy was noted in 384 of 396 patients (97%). Real-world data on intravitreal pegcetacoplan treatment identifies clinician practice patterns and demonstrates an acceptable safety profile, with complications leading to long-term vision loss following pegcetacoplan administration being rare in this cohort."

Journal • Real-world evidence • Age-related Macular Degeneration • Cardiovascular • Dry Age-related Macular Degeneration • Glaucoma • Hematological Disorders • Inflammation • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis • Vasculitis

Short-Term Changes in Intraocular Pressure Following Intravitreal Injection of Pegcetacoplan. (PubMed, J Vitreoretin Dis) - "To determine short-term changes in intraocular pressure (IOP) after intravitreal injection of 0.1 mL pegcetacoplan (Syfovre; Apellis Pharmaceuticals) for the treatment of geographic atrophy (GA)...Following pegcetacoplan injections, immediate IOP elevation was observed, which gradually declined within the first 30 minutes. Eyes with higher baseline IOP or a history of glaucoma exhibited higher postinjection IOP."

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

Apellis Announces 5-Year GALE Data Showing SYFOVRE (pegcetacoplan injection) Delayed Progression of Geographic Atrophy by ~1.5 Years (GlobeNewswire) - "The results demonstrate that both every-other-month and monthly SYFOVRE delayed GA lesion growth by approximately 1.5 years in patients with nonsubfoveal GA when compared to sham/projected sham....The safety profile of SYFOVRE through five years remained consistent with previously reported data."

P3 data • Age-related Macular Degeneration

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

A Prospective, Multicenter, Open-Label, Observational Phase 4 Study to Evaluate Real-World Safety, Tolerability, and Treatment Patterns of Pegcetacoplan (Syfovre) in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P=N/A | N=300 | Active, not recruiting | Sponsor: Apellis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

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

Plain language summary of disease activity and therapeutic response to pegcetacoplan for geographic atrophy identified by deep learning-based analysis of OCT. (PubMed, Immunotherapy) - No abstract available

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

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

GALE: An Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan (APL-2) in Subjects With Geographic Atrophy Secondary to AMD (clinicaltrials.gov) - P3 | N=792 | Completed | Sponsor: Apellis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | N=1200 ➔ 792 | Trial completion date: Sep 2026 ➔ Sep 2025

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

A Phase 2, Randomized, Placebo Controlled, Multicenter, Masked Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Multidose APL 3007 in Combination With Syfovre/Pegcetacoplan (APL-2) in Patients Diagnosed With Geographic Atrophy Secondary to Age Related Macular Degeneratio (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Apellis Pharmaceuticals, Inc.

New P2 trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Study to Evaluate a Pegcetacoplan (Syfovre®) Prefilled Syringe (clinicaltrials.gov) - P3 | N=36 | Not yet recruiting | Sponsor: Apellis Pharmaceuticals, Inc.

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

VERDANT: A Study to Test Whether BI 771716 Helps People With an Advanced Form of Age-related Macular Degeneration (AMD) Called Geographic Atrophy (clinicaltrials.gov) - P2 | N=188 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

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

VERDANT: A Study to Test Whether BI 771716 Helps People With an Advanced Form of Age-related Macular Degeneration (AMD) Called Geographic Atrophy (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Feb 2027 ➔ Oct 2026

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

Study to Assess the Adverse Events and How Intravitreal ABBV-6628 Moves Through the Body of Adult Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P1/2 | N=66 | Recruiting | Sponsor: AbbVie

Adverse events • New P1/2 trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Real-World Experience with Intravitreal Pegcetacoplan for the Treatment of Geographic Atrophy in Age-Related Macular Degeneration. (PubMed, Am J Ophthalmol) - "Eyes treated with pegcetacoplan after 1 year had a 37% reduction in GA growth rate compared with their prior annual growth rate. Pegcetacoplan slowed the growth for foveal and non-foveal GA at a similar rate. Most of the pegcetacoplan-associated exudation was not due to detectable MNV."

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

Dynamics of the EZ/RPE Loss Ratio on OCT Over Time During Geographic Atrophy Progression and Treatment With Pegcetacoplan. (PubMed, Invest Ophthalmol Vis Sci) - P3 | "OCT volumes of patients from the OAKS (NCT03525613) and DERBY (NCT03525600) trials, two phase III prospective randomized trials of GA treated with sham, intravitreal pegcetacoplan monthly (PM) and every other month (PEOM) were included...The change in EZ/RPE loss ratios at month 12 remained to be predictive for disease activity and therapeutic response, providing insights into disease mechanisms and relevant guidance for GA management in clinical practice. The EZ/RPE loss ratio decreased either due to advanced GA or induced by therapy in treated patients versus sham."

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

Apellis Pharmaceuticals Reports Second Quarter 2025 Financial Results (The Manila Times) - "Announced capped royalty purchase agreement with Sobi under which Apellis receives up to $300 million for 90% of ex-U.S. royalties of Aspaveli (pegcetacoplan); Generated $178 million in 2Q 2025 revenues, including $171 million in U.S. net product sales; SYFOVRE (pegcetacoplan injection) injection demand grew 6% quarter-over-quarter, with U.S. net product revenue of $151 million...Sobi, the Company’s exclusive ex-U.S. commercialization partner, expects an opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) for its indication extension application for Aspaveli (the brand name for EMPAVELI outside the U.S.) before year-end 2025"

CHMP • Commercial • CNS Disorders • Dry Age-related Macular Degeneration • Glomerulonephritis • Lupus • Paroxysmal Nocturnal Hemoglobinuria

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

VERDANT: A Study to Test Whether BI 771716 Helps People With an Advanced Form of Age-related Macular Degeneration (AMD) Called Geographic Atrophy (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Boehringer Ingelheim | Initiation date: May 2024 ➔ Jan 2025

Trial initiation date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Sterile Intraocular Inflammation Following Intravitreal Injections: Pathogenesis, Clinical Features, and Management. (PubMed, Int Ophthalmol Clin) - "Epidemiologic data show variable incidence across agents, with brolucizumab demonstrating higher rates of inflammation compared with ranibizumab or aflibercept. Treatment includes corticosteroids and discontinuation of the offending agent, with rare cases requiring surgical intervention. As the therapeutic landscape expands, heightened awareness and standardized evaluation of postinjection inflammation are critical to improving safety and preserving vision."

Journal • Review • Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis • Vasculitis

VERDANT: A Study to Test Whether BI 771716 Helps People With an Advanced Form of Age-related Macular Degeneration (AMD) Called Geographic Atrophy (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Boehringer Ingelheim | Initiation date: Jan 2025 ➔ May 2024

Trial initiation date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Visual Acuity and Quality of Life Outcomes with Pegcetacoplan Treatment: A Post Hoc Analysis from the OAKS and DERBY Trials. (PubMed, Am J Ophthalmol) - "Pegcetacoplan treatment demonstrated a potentially meaningful slower decline in visual acuity and QoL for patients with GA lesions ≥250 μm from the foveal center. The change in visual acuity and QoL seen with pegcetacoplan treatment for patients with GA lesions <250 μm from the foveal center were within the limits of variability."

HEOR • Journal • Retrospective data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Prospective, Multicenter, Open-Label, Observational Phase 4 Study to Evaluate Real-World Safety, Tolerability, and Treatment Patterns of Pegcetacoplan (Syfovre) in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Apellis Pharmaceuticals, Inc. | Trial completion date: Oct 2027 ➔ Jun 2028 | Trial primary completion date: Oct 2027 ➔ Jun 2028

Real-world evidence • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders