Empaveli (pegcetacoplan SC) / SOBI, Biogen - LARVOL DELTA

Breakthrough Hemolysis in Paroxysmal Nocturnal Hemoglobinuria: Mechanistic Insights and Management Strategies. (PubMed, Transfusion) - "This article provides the authors' assessments highlighting the complexity of BTH in PNH patients receiving complement inhibitors, particularly in the setting of TPE and transfusion. Evaluation should consider potential precipitants of BTH, including iatrogenic drug removal and complement-amplifying conditions such as transfusions. Adjunctive C5 inhibition may be required in acute settings, and further studies are needed to define optimal dosing strategies."

Journal • Review • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Thrombosis • Transplantation • CD55 • CD59

Complement targeting in autoimmune diseases. (PubMed, Curr Opin Hematol) - "Recognizing complement's role in the pathophysiology of hematological and autoimmune diseases has driven effective new therapies. Comprehensive profiling complement biomarkers, now feasible through complementomics in fluids and tissues, may reveal responsive endotypes and optimal cascade steps to target in diseases where complement is implicated but trials have not yet matched the right drug to the right patients."

Journal • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Systemic Lupus Erythematosus

Clinical improvement of acquired partial lipodystrophy in an adolescent with C3 glomerulopathy treated with pegcetacoplan. (PubMed, Pediatr Nephrol) - "Despite treatment with mycophenolate mofetil and tacrolimus, kidney function deteriorated, proteinuria increased, and she developed marked faciotruncal lipoatrophy with a 10-kg weight loss. Within 40 weeks, the patient recovered her usual body weight with marked clinical improvement in subcutaneous fat distribution. This observation suggests that pegcetacoplan may represent a novel therapeutic option for APL."

Journal • Complement-mediated Rare Disorders • Glomerulonephritis • Lipodystrophy • Metabolic Disorders • Nephrology • Rare Diseases • Renal Disease

A Real World Effectiveness Study of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) (clinicaltrials.gov) - P=N/A | N=165 | Active, not recruiting | Sponsor: Swedish Orphan Biovitrum | Recruiting ➔ Active, not recruiting

Enrollment closed • Real-world evidence • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • HP

SEISMIC: A multi-stakeholder summit addressing access issues in diagnosis and treatment of C3G nephropathy and IC-MPGN. (PubMed, Kidney Int) - "Two new therapeutic agents, iptacoplan and pegcetacoplan, that target proximal steps in the cascade, have demonstrated to be effective and have been approved for use in patients with C3G alone and with C3G/IC-MPGN, respectively...This report summarizes the deliberations and recommendations that emerged from the SEISMIC (Addressing access issues in diagnosis and treatment of C3G nephropathy and IC-MPGN) summit in July 2025. The meeting assembled a broad panel of experts and patients and addressed the following three aims: 1) define issues in proper and timely diagnosis of this complex disease spectrum, 2) assess management strategies in light of the availability of this new class of therapeutic agents, and 3) identify barriers to access to care and treatment with these new therapeutic agents and design strategies to surmount them."

Journal • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Renal Disease

Complement-targeted therapies for C3 glomerulopathy and atypical hemolytic uremic syndrome: a time-limited rapid systematic review with narrative synthesis. (PubMed, Front Med (Lausanne)) - "The abbreviated timeframe was chosen to inform clinical practice following the March 2025 FDA approval of iptacopan and the July 2025 FDA approval of pegcetacoplan for C3G, at a time when clinicians required timely guidance on emerging therapeutic options...In C3G, eculizumab showed heterogeneous responses...This review employed narrative synthesis without meta-analysis; readers should not interpret reported percentages as pooled estimates. CRD420261364711 (rapid registration, 9 April 2026)."

Journal • Review • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Infectious Disease • Meningococcal Infections • Nephrology • Renal Disease

Indirect treatment comparisons find enhanced effectiveness of pegcetacoplan versus crovalimab in both complement inhibitor-naïve and -experienced patients with paroxysmal nocturnal hemoglobinuria. (PubMed, J Comp Eff Res) - P3 | "Materials & In the C5i-naive, an unanchored matching-adjusted indirect comparison (MAIC) was conducted with patient-level data for pegcetacoplan-versus-best-supportive-care from PRINCE (NCT0408560) and published data for crovalimab-versus-eculizumab from COMMODORE 2 (NCT04434092)/COMMODORE 3 (NCT04654468). In the C5i-experienced, all outcomes significantly (p < 0.05) favored pegcetacoplan. Pegcetacoplan provides high clinical advantages across the full PNH treatment pathway."

Journal • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Global research landscape of C3 glomerulopathy: A bibliometric analysis. (PubMed, Clin Nephrol) - "Global research on C3G has evolved from descriptive pathology toward precision complement therapeutics. However, significant geographical disparities persist, emphasizing the need for stronger international collaboration and equitable access to emerging complement inhibitors."

Journal • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Pediatrics • Renal Disease

Pegcetacoplan as a targeted C3 inhibitor in C3 glomerulopathy and immune-complex MPGN. (PubMed, Ann Med Surg (Lond)) - No abstract available

Journal • Complement-mediated Rare Disorders • Glomerulonephritis

Real-World Effectiveness and Safety of Pegcetacoplan in Patients With C3G or IC-MPG: A Multi-Country Study (clinicaltrials.gov) - P4 | N=150 | Recruiting | Sponsor: Swedish Orphan Biovitrum

New P4 trial • Real-world evidence • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology

Methodological pitfalls in indirect treatment comparisons: insights from a recent systematic review and analysis for C3 glomerulopathy. (PubMed, J Comp Eff Res) - "This appraisal evaluates the feasibility of applying ITC principles to compare Phase III trials of iptacopan (APPEAR-C3G) and pegcetacoplan (VALIANT) in the absence of head-to-head evidence. Consequently, payers, decision makers, and HTA bodies should interpret existing C3G ITCs with caution. These findings inform broader application of ITC methods in rare diseases, identifying areas for future evidence generation and analytical innovation."

Journal • Review • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Rare Diseases • Renal Disease

Site-targeted proximal complement C3 inhibition, but not C5 blockade, attenuates neurodegeneration in a mouse model of amyotrophic lateral sclerosis: Implications for failed clinical trials. (PubMed, Neurotherapeutics) - "Failed trials of C5 inhibition - ravulizumab (CHAMPION-ALS) and zilucoplan (ATHLEET/HEALEY ALS Trial), and of systemic C3 inhibition (pegcetacoplan, MERIDIAN) underscore this mechanistic gap. Proximal C3 activation products, not C5a or MAC, are the dominant drivers of complement-mediated neurodegeneration in the hSOD1G93A model of ALS. Site-targeted C3 inhibition may address the mechanistic limitation underlying recent clinical trial failures and represents a translationally justified therapeutic strategy."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation

Pivotal Clinical Trials in C3 Glomerulopathy: answers and remaining uncertainties. (PubMed, Nephrol Dial Transplant) - "The publication of pivotal phase 3 trials evaluating proximal complement inhibitors -iptacopan, a selective factor B inhibitor, and pegcetacoplan, a C3 inhibitor- marks a turning point in the management of C3G and IC-MPGN. We emphasize the need for long-term outcome studies, precision-based therapeutic strategies, and pragmatic real-world data. Ultimately, the challenge ahead is not whether complement inhibition is effective but how best to deploy these therapies to maximize durable benefit, minimize risk, and ensure equitable access."

Journal • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Renal Disease

Beyond Terminal Blockade: A Mechanism-Based Approach to Complement Inhibitor Selection in Paroxysmal Nocturnal Hemoglobinuria. (PubMed, Drug Des Devel Ther) - "The proximal complement inhibitors pegcetacoplan (C3), iptacopan (Factor B), and danicopan (Factor D) address EVH-driven anemia but have not been evaluated in trials powered for thrombosis prevention, creating an asymmetry in the evidence base that demands explicit clinical reasoning. This review proposes a phenotype-driven longitudinal management strategy stratifying treatment decisions by dominant disease mechanism, thrombotic risk, and practical treatment context. Diagnostic approaches to differentiating EVH‑dominant, BMF‑dominant, and overlap phenotypes in the relevant patient subsets, comparative evidence across inhibitor classes, and mechanism-based escalation strategies are addressed in sequence, alongside high-risk clinical scenarios and an evidence-gap analysis to guide future research."

Journal • Review • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Venous Thromboembolism

Proximal Versus Terminal Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria with Residual Anemia: A Systematic Review and Pairwise Meta-Analysis of Randomized Controlled Trials (ISTH 2026) - "Proximal complement inhibitors targeting C3 (pegcetacoplan), factor B (iptacopan), or factor D (danicopan) address both intravascular and extravascular hemolysis. Table or Figure Upload (1) Table 1. Pooled efficacy outcomes: proximal inhibitor monotherapy versus C5 inhibitors Page 2 DOI*10.1016/j.rpth.2026.104819"

Retrospective data • Review • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Switching between complement inhibitors in paroxysmal nocturnal hemoglobinuria: Analysis of strategy, efficacy, and safety. (PubMed, Hemasphere) - "Clinical trials for the approved PI pegcetacoplan, iptacopan, and C5i + danicopan had clear protocols for changing from terminal to PI, extrapolated into real-world practice. Patients should be monitored closely for hemolysis, especially when changing from proximal-to-terminal inhibition. Prospective clinical/laboratory analysis is recommended for further clarification management for this patient group."

Journal • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Complement System Inhibitors in Nephrology: A Comprehensive Review. (PubMed, G Ital Nefrol) - "Terminal complement inhibitors (eculizumab and ravulizumab) have revolutionized the treatment of atypical haemolytic uremic syndrome, demonstrating remarkable improvements in renal outcomes and survival. Proximal pathway inhibitors targeting Factor B (Iptacopan) and C3 (pegcetacoplan) show promise in C3 glomerulopathy and IgA nephropathy, with recent phase 3 trials demonstrating significant proteinuria reduction. Additional applications include immune complex membranoproliferative glomerulonephritis and ANCA-associated vasculitis, in which complement activation contributes to disease pathogenesis. However, these agents present unique challenges, including infection risk, particularly meningococcal disease, cost considerations, and uncertainty regarding optimal treatment duration."

Journal • Review • ANCA Vasculitis • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Lupus Nephritis • Meningococcal Infections • Nephrology • Renal Disease • Vasculitis

Canada’s Drug Agency Issues Positive Reimbursement Recommendation for EMPAVELI (pegcetacoplan) for the Treatment of C3G and Primary IC-MPGN (GlobeNewswire) - "The CDA recommendation was informed by data from the Phase 3 VALIANT study, the largest single clinical trial conducted in patients with C3G and primary IC-MPGN. The study evaluated pegcetacoplan in 124 patients aged 12 years and older and demonstrated clinically meaningful reductions in proteinuria, stabilization of kidney function, and clearance of C3 deposits."

Reimbursement • Complement-mediated Rare Disorders • Glomerulonephritis • Renal Disease

A Real World Effectiveness Study of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) (clinicaltrials.gov) - P=N/A | N=200 | Recruiting | Sponsor: Swedish Orphan Biovitrum | Trial primary completion date: Aug 2026 ➔ Aug 2029

Real-world evidence • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • HP

A Beacon of Hope: Pegcetacoplan for Adolescents with C3 Glomerulopathy or Primary Immune Complex Membranoproliferative GN. (PubMed, Clin J Am Soc Nephrol) - No abstract available

Journal • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Pediatrics • Renal Disease

Biogen ends Apellis research programs, cuts ‘small number’ of roles after $5.6B buyout (FierceBiotech) - "As part of the move, 'a small number of roles within the research organization have been eliminated,” the spokesperson added. Biogen continues to assess Apellis’ clinical and preclinical portfolio to “further evaluate strategic fit,' the company representative said...In cutting these research efforts, Biogen is making explicit its desire to focus on Apellis’ Empaveli and Syfovre, marketed drugs which share the active ingredient pegcetacoplan and which served as the centerpiece of the March deal....Besides the approved Apellis meds, the biotech had been conducting research on clinical-stage asset APL-3007 before the merger, according to its pipeline."

Licensing / partnership • Ophthalmology • Paroxysmal Nocturnal Hemoglobinuria

Efficacy and Safety of the C3 Inhibitor Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis. (PubMed, Eur J Haematol) - "Pegcetacoplan demonstrates consistent efficacy signals across key hematologic endpoints and an acceptable safety profile, supporting its potential role as an important therapeutic option, particularly in patients with persistent extravascular hemolysis despite C5 inhibition."

Journal • Retrospective data • Review • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Sobi.PEGCET-402: Real-world study to evaluate how effective and safe Pegcetacoplan is in patients with rare kidney diseases called C3G or IC-MPGN in multiple countries (PRISMC3) (clinicaltrialsregister.eu) - P4 | N=69 | Not yet recruiting | Sponsor: Swedish Orphan Biovitrum AB (publ)

New P4 trial • Real-world evidence • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease

Pegcetacoplan as Prophilaxis to Prevent Relapse Following Kidney Transplant in a Difficult C3 Glomerulopathy Child with a Multifactorial Genetic Background (ATC 2026) - "Initial therapy included prednisone, cyclosporine, and ACE inhibition...Mycophenolate was not tolerated and eculizumab was ineffective... This case documents the first reported use of pegcetacoplan as prophylaxis against post-transplant C3G recurrence with favorable medium-term outcome and illustrates the synergistic impact of complement dysregulation and podocyte weakness and ."

Clinical • Chronic Kidney Disease • Complement-mediated Rare Disorders • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease • Transplantation

Pegcetacoplan for Posttransplant Patients with Complement 3 Glomerulopathy or Primary (Idiopathic) Immune-Complex Membranoproliferative Glomerulonephritis (ATC 2026) - P2, P3 | "Six months of pegcetacoplan treatment was safe and well tolerated for posttransplant patients with C3G and primary IC-MPGN. Patients achieved decreased proteinuria, stable eGFR, and improved C3 staining."

Clinical • Post-transplantation • Chronic Kidney Disease • Glomerulonephritis • Lupus Nephritis • Nephrology • Transplantation