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

Complement Inhibition in IgA Nephropathy (KSN 2025) - "In a phase 3 trial, iptacopan achieved a ~38% greater reduction in proteinuria versus placebo at 9 months on top of standard care, leading to its accelerated approval as the first complement inhibitor for IgAN. An antisense oligonucleotide targeting factor B (IONIS-FB-LRx) similarly reduced proteinuria by ~44% in a phase 2 study, and a phase 3 trial is ongoing. In contrast, the lectin pathway inhibitor narsoplimab (anti-MASP-2) did not meet its primary endpoint in a phase 3 trial, despite promising early-phase results. We will also discuss other investigational approaches, including proximal complement blockade at C3 (pegcetacoplan) and terminal pathway inhibition (e.g., C5 monoclonal antibodies and C5a receptor antagonists). While terminal complement inhibitors like eculizumab have shown anecdotal benefits in severe IgAN, robust trial data in primary IgAN are awaited...While targeting the alternative pathway has shown the most consistent benefit to date, additional..."

Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Lupus Nephritis • Renal Disease

Navigating the paroxysmal nocturnal hemoglobinuria (PNH) landscape. (PubMed, Clin Adv Hematol Oncol) - "C5 inhibitors approved by the US Food and Drug Administration (FDA) include eculizumab (administered intravenously every 2 weeks), ravulizumab (administered intravenously every 8 weeks), and, most recently, crovalimab (administered subcutaneously every 4 weeks)...The C3 inhibitor pegcetacoplan (administered subcutaneously twice weekly) and the factor B inhibitor iptacopan (administered orally twice daily), both used as single agents, have demonstrated effective control of hemolysis with increased hemoglobin and transfusion avoidance in both C5 inhibitor-naive and C5 inhibitor-experienced patients with clinically significant extravascular hemolysis. The factor D inhibitor danicopan (administered orally 3 times a day) is used as an add-on to ravulizumab or eculizumab and offers a combination approach by targeting both terminal complement and the alternative pathway. Breakthrough hemolysis in the event of a strong complement trigger is possible on any complement inhibitor,..."

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

Apellis signs royalty purchase deal with Sobi for Aspaveli (MSN News) - "Apellis Pharmaceuticals...announced a new agreement with Sobi...involving a capped royalty purchase related to Empaveli, its blood disorder treatment. In this arrangement, Apellis will obtain up to $300M in return for 90% of its future royalties outside the U.S. for its product, Empaveli...The company will receive an upfront payment of $275M, along with potential milestone payments totaling up to $25M, contingent upon receiving EMA approval for conditions C3G and IC-MPGN."

Commercial • Glomerulonephritis

Interim symptom and treatment data from an app-based study on paroxysmal nocturnal hemoglobinuria (ISTH 2025) - P | "At enrollment, participants report baseline health (medical history, treatment history, and demographic information) and customize their Folia Health app profile by adding symptoms they are experiencing and treatments they are taking (e.g. iptacopan, danicopan, ravulizumab, pegcetacoplan). Tables 1 and 2 outline most common symptoms and PNH treatments selected for tracking. Table or Figure Upload"

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

NETWORK META-ANALYSIS COMPARING THE EFFICACY OF DIFFERENT COMPLEMENT PATHWAY INHIBITORS FOR THE TREATMENT OF PAROXYSMAL NOCTURNAL HEMATURIA (EHA 2025) - "Aims: We performed a systematic review and network meta-analysis comparing the efficacy of four new complement inhibitors: pegcetacoplan, iptacopan, danicopan, and crovalimab, to aid in the decision-making process regarding the optimal drug choice for the treatment of PNH. Proximal complement inhibitors are more effective than eculizumab/ravulizumab in controlling anemia-related symptoms of PNH. While there is no significant difference between novel proximal complement inhibitors, our results suggest that iptacopan or pegcetacoplan may be the preferred drug. Additional factors such as route and frequency of drug administration should be taken into consideration when selecting the optimal treatment choice for the patients."

Retrospective data • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

A SINGLE INSTITUTION EXPERIENCE OF IPTACOPAN IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (EHA 2025) - "Mean changes from baseline to 3 months included the following: Hgb (11.9±1.35 g/dL to 12.3±1.76 g/dL), reticulocytes (.130±.08 cells/µL to .083±.02 cells/µL), LDH (485±541 IU/L to 457±129 IU/L), PNH erythrocyte clone size + 17.0% and granulocyte clone size +30.9%.As to the CI-switched cases, 25 patients had suboptimal response to ravulizumab (n=16), pegcetacoplan (n=6), and eculizumab (n=3). Iptacopan was associated with significant improvements in hemolysis markers and hemoglobin levels at 3 months. Although longer follow-up is needed to confirm durability and safety, these results suggest that oral factor B inhibition can be an effective and convenient alternative for patients with PNH, particularly for those who are either treatment-naïve or have an inadequate response to existing parenteral therapies."

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

INDIRECT TREATMENT COMPARISON OF IPTACOPAN VS. PEGCETACOPLAN IN COMPLEMENT INHIBITOR NAÏVE PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS (EHA 2025) - P3 | "In the absence of a H2H trial, this ITC suggests that patients on iptacopan might have significantly higher increase in Hb and lower transfusion rates, with similar effectiveness in LDH control, when compared with pegcetacoplan. These findings should be interpreted within the framework of STC, with its strengths and limitations."

Clinical • Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Pegcetacoplan Promotes Better Blood Counts and Fewer Transfusions for Patients With PNH (DocWire) - P=Obs | N=200 | COMPLETE (NCT05776472) | "A study presented at the European Hematology Association 2025 Congress highlights the real-world benefit of pegcetacoplan for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), an uncommon and severe blood disorder. The results are based on an interim analysis of the COMPLETE study, which is monitoring the efficacy of this treatment...The average hemoglobin level, a primary indicator of red blood cells, increased by 2.3 g/dL after six months of pegcetacoplan therapy. Over 50% of patients experienced an increase in their hemoglobin levels by 2 g/dL or more, and the percentage of patients attaining healthy hemoglobin levels (12 g/dL or above) rose to 42%, compared to 4% previously. Researchers observed the same pattern after 12 months in those who remained on treatment....Other indicators of blood health also improved."

Observational data • Real-world evidence • Paroxysmal Nocturnal Hemoglobinuria

AT THE HEART OF COLD: EXPLORING AND ADVANCING THERAPIES IN COLD AGGLUTININ DISEASE BASED ON 7 CASES (EHA 2025) - "Treatment mainly involves avoiding cold exposure in conjunction with medical treatments, such as rituximab as first-line therapy, either alone or in combination with bendamustine. Cold agglutinin disease (CAD) is an idiopathic clonal B lymphoproliferative disorder without malignancy signs, characterized by the presence of antibodies capable of recognizing red blood cell antigens at low temperatures via complement activation. Its manifestations primarily include fatigue, anemia of varying severity, and ischemic signs exacerbated by cold. From a therapeutic perspective, only patients with poorly tolerated anemia below 8 g/dl, with transfusion dependence or severe circulatory symptoms, should be treated."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Congestive Heart Failure • Diabetes • Fatigue • Heart Failure • Hematological Disorders • Hypertension • Metabolic Disorders • Oncology • Retinal Disorders

TREATMENT OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS WITH COMPLEMENT INHIBITORS - EXPERIENCE OF A SINGLE CENTER (EHA 2025) - "Twenty-one patients with hemolytic PNH were treated with C5 complement inhibitors eculizumab or ravulizumab...Patients with insufficient response to C5 inhibitors were switched to treatment with C3 inhibitor pegcetacoplan.Complete, very good and good response to the C5 inhibitors was present in 13 out of 21 patients (61,6%), 8 patients did not achieve sufficient response to the treatment, 2 of them without any effect of therapy developed subsequently myelodysplastic syndrome (MDS)... The treatment with C5 and C3 complement inhibitors substantially improved prognosis of our PNH patients, administration of the inhibitors resulted in transfusion independency or in a substantial decrease of number of red blood cell transfusions, no thrombotic complications occurred after starting the treatment. Our results show (similarly as other studies) that currently almost all PNH patients treated with complement inhibitors may survive 10 years or more with substantially improved..."

Clinical • Aplastic Anemia • Chronic Kidney Disease • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Nephrology • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease

REAL-WORLD EFFECTIVENESS OF RAVULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: THE US POLESTAR CHART REVIEW STUDY (EHA 2025) - "These real-world data confirm the findings from clinical trials in a broad population of patients with PNH. Among adults with PNH in the US, ravulizumab treatment was associated with significant and meaningful reductions in LDH levels and improvements in hemoglobin levels, irrespective of whether patients were Ci-naive or had prior experience with either eculizumab or pegcetacoplan. Among patients who were Ci-naive, significant and meaningful improvements in ARC were also observed after ravulizumab initiation."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Review • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

BENEFIT OF PEGCETACOPLAN IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA IRRESPECTIVE OF BASELINE TRANSFUSION STATUS (EHA 2025) - "Key efficacy parameters were achieved and maintained long-term for up to 192 weeks irrespective of baseline transfusion status across C5i-experienced and -naïve pts.The results highlight the benefit of initiating PEG in C5i-experienced or -naïve pts, regardless of transfusion burden, a conventional marker of PNH severity."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

A BENEFIT ASSESSMENT OF PEGCETACOPLAN DOSE INCREASE IN THE PHASE 3 PEGASUS TRIAL OF PNH PATIENTS WITH DIFFICULT-TO-CONTROL DISEASE (EHA 2025) - P3 | "In the Phase 3 PEGASUS trial of pts with persistent anaemia despite C5i treatment, pegcetacoplan demonstrated significant and sustained improvements in haematologic and clinical parameters versus C5i eculizumab.Pegcetacoplan is approved by FDA for adult PNH pts and by EMA for adult PNH pts with haemolytic anaemia.A serum concentration threshold of 442 μg/mL is required for pegcetacoplan to produce 90% of the proportional maximal change from baseline (EC90) in lactate dehydrogenase (LDH) improvement for C5i-treated pts (data on file). The majority of evaluable PEGASUS pts (8/12) who received pegcetacoplan Q3D upon LDH >2× ULN benefited from dose up-titration. These 8 pts experienced LDH decrease with no new safety signals.As per pegcetacoplan's label, dose increase from 1080 mg BIW to Q3D should be considered if a patient experiences an LDH increase of >2× ULN."

Clinical • P3 data • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Thrombosis

EARLY RESPONSE IN COMPLEMENT INHIBITOR NAÏVE PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA TREATED WITH PEGCETACOPLAN IN THE PHASE 3 PRINCE TRIAL (EHA 2025) - P3 | "This post-hoc analysis demonstrates a high response rate to first-line usage of PEG as early as 4 weeks of initiating treatment. Pts benefited from immediate and sustained improvements in key hematological parameters, including those required to enable symptom improvement (Hb) and demonstrate control of hemolysis (LDH).In escape pts experiencing a Hb drop ≥2 g/dL before PEG initiation, PEG led to rapid hemolysis control in most pts. These results provide further evidence to support PEG use in first-line treatment of adult PNH pts."

Clinical • P3 data • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

REAL-WORLD RETROSPECTIVE ANALYSIS OF PEGCETACOPLAN EFFECTIVENESS IN PATIENTS FROM CEE COUNTRIES WITH PNH AND NO OPTIMAL RESPONSE TO C5 INHIBITORS (EHA 2025) - "Pegcetacoplan therapy was indicated based on experiencing EVH during C5 inhibitor therapy (eculizumab n=19, ravulizumab n=6, crovalimab n=1). This is the only real-world analysis of the pegcetacoplan effectiveness in PNH patients from CEE countries, not responding optimally to C5 inhibitors. We confirmed the high efficacy of pegcetacoplan in a group of PNH patients experiencing EVH during C5 inhibitor therapy, especially in terms of improving hemoglobin levels and normalizing reticulocytosis with unchanged LDH values. Given the relatively small patient population of the registration study and the sparse data from single real-world analyses, this analysis provides valuable data on the effectiveness of pegcetacoplan therapy, particularly with detailed characteristics of BTH events and management strategies in real-world settings."

Real-world • Real-world evidence • Retrospective data • Cardiovascular • Hematological Disorders • Infectious Disease • Influenza • Pneumonia • Respiratory Diseases • Thrombosis

INTERIM ANALYSIS OF THE ONGOING COMPLETE STUDY ON THE REAL-WORLD EFFECTIVENESS OF PEGCETACOPLAN IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) (EHA 2025) - P | "COMPLETE enrolls a wide range of pts reflecting real-world PNH treatment with pegcetacoplan.After 6 months on pegcetacoplan, pts experienced significant improvements in hematologic parameters, with a median Hb increase of 2.3 g/dL, which were sustained at 12 months.Findings from COMPLETE aim to broaden our understanding of pegcetacoplan's real-world effectiveness and safety in PNH patients."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

FPT2002: Pegcetacoplan in Action: Transforming Paroxysmal Nocturnal Haemoglobinuria (PNH) Care with C3 Inhibition (for HCPs only) (EHA 2025) - "Sponsored by Swedish Orphan Biovitrum AB"

Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria

A Study of Pegcetacoplan in Pediatric Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Apellis Pharmaceuticals, Inc. | Trial completion date: Oct 2024 ➔ Dec 2028 | Trial primary completion date: Apr 2024 ➔ Dec 2028

Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Pediatrics • Rare Diseases

Pegcetacoplan for C3G and primary (idiopathic) IC-MPGN: 52-week results from the phase 3 VALIANT trial show sustained efficacy (ERA 2025) - P3 | "Results from the VALIANT OLP support the efficacy and safety observed during the RCP. Patients who completed the VALIANT OLP were eligible to enter the VALE long-term extension study. With one year of therapy, the robust proteinuria decrease achieved with pegcetacoplan in the RCP was maintained in the OLP; similar robust reductions were achieved for patients who switched from placebo to pegcetacoplan, confirming the broad effect of pegcetacoplan in a heterogenous patient population."

Clinical • Late-breaking abstract • P3 data • Complement-mediated Rare Disorders • Glomerulonephritis • Infectious Disease • Inflammation • Lupus Nephritis • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Pegcetacoplan Demonstrates Clinically Significant Responses in C3G and Primary (Idiopathic) IC-MPGN Patients With or Without Concomitant Immunosuppression in VALIANT (ERA 2025) - P3 | "Current treatments, such as mycophenolate mofetil (MMF) and corticosteroids, are used off-label, primarily targeting inflammatory changes rather than the underlying disease mechanism...Participants were permitted to continue pre-existing MMF, glucocorticoids (maximum dose 20 mg prednisone daily or equivalent) and other immunosuppressive therapies, provided that the doses of these, as well as other drugs impacting proteinuria, remained stable throughout the randomized controlled period and preceding 12-week screening period... In this pre-specified analysis, C3G/primary IC-MPGN pts receiving stable concomitant IS achieved robust proteinuria reduction, glomerular C3 reduction, and eGFR stabilization with PEG treatment, with outcomes similar to pts without concomitant IS treatment. PEG was well-tolerated with no new safety signals and no difference in adverse event profiles with/without IS treatment."

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis • Infectious Disease • Lupus Nephritis • Meningococcal Infections • Novel Coronavirus Disease • Pneumonia • Rare Diseases • Respiratory Diseases

Targeted Treatment With Pegcetacoplan for Adolescents With C3G or Primary (Idiopathic) IC-MPGN in the VALIANT Phase 3 Trial (ERA 2025) - P3 | "Results from VALIANT demonstrate that PEG, a C3/C3b inhibitor that blocks C3 overactivation, is the only treatment to induce clinically meaningful proteinuria reduction and eGFR stabilization compared with placebo in adolescent pts with C3G or primary IC-MPGN. The treatment was well-tolerated."

P3 data • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Rare Diseases

Pegcetacoplan Treatment Effect in Patients With Nephrotic Range Proteinuria: Results From the VALIANT Phase 3 Study in Patients With C3G or Primary (Idiopathic) IC-MPGN (ERA 2025) - P3 | "Current treatments, such as mycophenolate mofetil (MMF) and corticosteroids, are used off-label, primarily targeting inflammatory changes rather than the underlying disease mechanism. In the VALIANT trial, C3G/primary IC-MPGN pts presenting with nephrotic range proteinuria demonstrated robust reductions in proteinuria and glomerular C3, eGFR stabilization, and serum albumin normalization, confirming a disease-modifying effect of PEG in this severe subpopulation. PEG was well-tolerated and the safety profile was consistent with previous reports."

Clinical • P3 data • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Rare Diseases • Renal Disease

Targeted Treatment With Pegcetacoplan for Post-Transplant Recurrent C3G or Primary (idiopathic) IC-MPGN in the VALIANT Phase 3 Trial (ERA 2025) - P3 | "Results from VALIANT demonstrate that PEG effectively halts the disease mechanism underlying C3G/primary IC-MPGN, indicating a profound disease-modifying effect. PEG, a C3/C3b inhibitor, is the first therapy to achieve significant and clinically meaningful improvements in the three key efficacy measures of proteinuria reduction, C3 renal deposit clearance, and stabilization of eGFR in pts with post- transplant recurrent C3G or primary IC-MPGN. The results of this subgroup analysis confirm that PEG is equally safe and efficacious in treating post-transplant recurrent or native C3G/primary IC-MPGN."

P3 data • Post-transplantation • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Rare Diseases • Transplantation

Real-world evidence for efficacy and safety of Iptacopan and Pegcetacoplan in patients with primary membranoproliferative glomerulonephritis (MPGN) (ERA 2025) - "Preceding therapies included steroid pulses (n=11 patients), oral prednisone (n=15), MMF (n=21), calcineurin inhibitors (n=3) and RAS inhibitors (n=23). Our real-world findings confirm impressive antiproteinuric and potentially GFR stabilizing effects of PCI in patients who demonstrated limited responsiveness to conventional immunosuppressive and nephroprotective treatment. The drugs appear to have a highly favourable safety profile."

Clinical • HEOR • Real-world • Real-world evidence • Complement-mediated Rare Disorders • Glomerulonephritis • Infectious Disease • Lupus Nephritis • Nephrology • Pediatrics • Pneumonia • Respiratory Diseases

Pegcetacoplan Treatment Appears to Halt Disease Progression in C3G and Primary (Idiopathic) IC-MPGN Patients: Results from the Phase 3 VALIANT Study (ERA 2025) - P3 | "Current treatments, such as mycophenolate mofetil (MMF) and corticosteroids, are used off-label, primarily targeting inflammatory changes rather than the underlying disease mechanism. PEG treatment led to an increase in serum C3 levels, a reduction in serum sC5b-9 and clearance of glomerular C3 deposition. Further, PEG treatment resulted in a significant and clinically meaningful decrease in UPCR to <0.5 g/g. These findings demonstrate a profound disease-modifying effect, regardless of baseline proteinuria levels."

Clinical • P3 data • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Rare Diseases