Soliris (eculizumab) / AstraZeneca - LARVOL DELTA

Ravulizumab demonstrates real-world effectiveness in patients with paroxysmal nocturnal hemoglobinuria: A US chart review study (ASH 2025) - "Complement inhibitor (Ci)-experienced patients had previous eculizumab or pegcetacoplan use pre-index; Ci-naive patients had no previous use of any Ci pre-index. (2025), which reported BT-IVH in 14.8% of C5i-naive (event rate: 1.0 per 10 PY) and 7.8% of eculizumab-experienced patients (event rate: 0.33 per 10 PY) with PNH over a follow-up period of up to 6 years (median: 3.9 and 2.7 years, respectively). Overall, this analysis supports the use of ravulizumab, with only 6–7 infusions per year, as an effective treatment for patients with PNH in the real-world setting."

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

Paroxysmal nocturnal hemoglobinuria: Transplant experience using post-transplant cyclophosphamide in a resource-limited setting (ASH 2025) - "On the other hand, complement inhibitors (eculizumab, ravulizumab) have emerged as effective treatments with lower toxicity, though they are not curative...MRD transplant patients received Fludarabine/Melphalan (Flu/Mel) and haploidentical transplant received standard Baltimore protocol...Among them, two patients developed CMV reactivation, which was well controlled with valganciclovir... Allogeneic HSCT remains a potentially curative but high risk option for PNH patients, particularly in resource limited settings. Our experience highlights the significant transplant related morbidity and mortality, even with modern GVHD prophylaxis such as PTCy.Given the availability of safer, though non-curative, therapeutic alternatives like complement inhibitors, urgent advocacy is needed. Patient groups, healthcare providers, policy-makers, and international aid organizations must collaborate to improve access to life-saving treatments in low-income countries."

Post-transplantation • Aplastic Anemia • Bone Marrow Transplantation • Cardiovascular • Chronic Graft versus Host Disease • Complement-mediated Rare Disorders • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Inflammation • Mucositis • Myelodysplastic Syndrome • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases • Thrombosis • Transplantation

PNH-driven hepatic vein thrombosis: A case of budd-chiari syndrome in disguise" (ASH 2025) - "Prompt diagnosis and initiation of complement inhibition therapy, such as eculizumab, can significantly improve prognosis. PNH should be considered in the differential diagnosis of young patients presenting with unexplained thrombotic phenomena and intravascular hemolysis."

Clinical • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hepatology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • CD55 • CD59

Optimizing PNH treatment with the complement inhibitor pegcetacoplan: A case report (ASH 2025) - "The current treatment landscape includes 6 approved complement cascade inhibitors: 3 C5 inhibitors (eculizumab, ravulizumab, crovalimab), 1 C3/C3b inhibitor (pegcetacoplan), 1 factor B inhibitor (iptacopan), and 1 factor D inhibitor used as add-on treatment (danicopan)...Concomitant medications included apixaban, penicillin, and folic acid. In November 2020, her platelets count declined, and a bone marrow evaluation was diagnostic for moderate aplastic anemia (55-65% cellularity for age) and she was started on eltrombopag and cyclosporin. Despite ravulizumab and eltrombopag treatments, the patient developed significant anemia related to extravascular hemolysis (hemoglobin, 5.7 g/dL; LDH, 495 U/L; C5, 26.1 mg/dL [high]; complement hemolytic activity 50 [CH50], 7 U/mL [low])...After receiving both pegcetacoplan and iptacopan for 1 week and rivaroxaban 10 mg once daily for 48 hours, pegcetacoplan treatment ended on May 16, 2024... For this patient with PNH, the..."

Case report • Clinical • Anorexia • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Successful retreatment of PNH with switch to ravulizumab and add-on danicopan after experiencing breakthrough hemolysis on pegcetacoplan: A case report (ASH 2025) - "Terminal complement inhibition with C5 inhibitors ravulizumab (Rav), the standard of care for PNH treatment, and eculizumab (Ecu) have provided effective control of terminal complement activity and IVH and decreased rates of thrombosis...The patient was treated intermittently with antithymocyte globulin and/or cyclosporine for ~5 years while receiving red blood cell transfusions... Hb, 11.8 g/dL; LDH, 351 U/L). The patient restarted Rav with 2 loading doses 2 weeks apart. The patient experienced 1 mild episode of BTH ~4 months after restarting Rav (Hb, 9.9 g/dL; LDH, 382 U/L), resolving rapidly with her scheduled dose of Rav."

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

Overview of treatment advances with complement inhibitors in patients with paroxysmal nocturnal hemoglobinuria (ASH 2025) - P3 | "The success of terminal C5 inhibitors emboldened researchers to investigate proximal complement inhibitors that have the potential to control both IVH and EVH, such as pegcetacoplan (C3/C3b inhibitor) and iptacopan (factor B inhibitor), as well as danicopan (factor D inhibitor) used as an add-on to C5 inhibitors...In the most recent analysis of the phase 3 ALPHA trial (NCT04469465), 57 patients (mean age 53 years) with PNH and residual clinically significant EVH (Hb ≤9.5 g/dL with ARC ≥120 × 10 9 /L) while receiving ravulizumab (63%) or eculizumab (37%) for a mean of 5 years were given danicopan in addition to their current C5 inhibitor for 12 weeks.[Kulasekararaj A, et al... Across clinical studies that included patients with PNH and Hb ≥10 g/dL after C5 inhibition, proximal complement inhibitors improved measures of residual anemia and quality of life to clinically significant degrees (increases of ≥2 g/dL in Hb levels and ≥3–5 points in FACIT-Fatigue..."

Clinical • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections • Otorhinolaryngology • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases • Thrombosis

User experience with pegcetacoplan on-body injector in patients with paroxysmal nocturnal hemoglobinuria (ASH 2025) - " Twelve patients with PNH (mean age, 46 years) previously treated with C5is (eculizumab, n=5; ravulizumab, n=7) and on pegcetacoplan for a mean of 18.2 months were recruited; 1 patient who had limited experience with the injector did not complete the interview. Most patients with PNH were satisfied with multiple aspects of their experience with the pegcetacoplan injector. Patients perceived the injector positively as it provides significant benefits, improving their quality of life and reducing treatment burden. Similar on-body delivery systems used by patients with relapsed/refractory multiple myeloma (phase 2 IZALCO and phase 3 IRAKLIA trials) were associated with low infusion-reaction rates, potentially leading to improved long-term adherence, patient quality of life, and practice efficiency [Parmar G, et al."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Low risk for meningococcal and other encapsulated bacteria infections with systemically administered pegcetacoplan in paroxysmal nocturnal hemoglobinuria and C3 glomerulopathies (ASH 2025) - P3 | "Clinical benefits of the initially available C5 inhibitors that blocked terminal complement activation (eculizumab, ravulizumab, crovalimab) paved the way for the development of proximal inhibitors, including the C3/C3b inhibitor pegcetacoplan, the factor B inhibitor iptacopan, and the add-on (to C5 inhibitors) factor D inhibitor danicopan. Understanding the safety profile of pegcetacoplan and other complement-targeted therapies, especially the risk for meningococcal and other encapsulated bacteria infections, will help physicians and patients make informed treatment decisions for individuals with complement-mediated conditions. For nearly over 7 years, systemically administered pegcetacoplan has had a consistently low rate of encapsulated bacteria infections in patients with PNH, C3G, or primary IC-MPGN. These findings may reflect effective risk mitigation strategies."

CNS Disorders • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Immunology • Infectious Disease • Influenza • Lupus Nephritis • Meningococcal Infections • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Pneumococcal Infections • Pneumonia • Primary Immunodeficiency • Rare Diseases • Respiratory Diseases • Septic Shock

Influenza A-triggered complement-mediated aHUS and high-grade block in a young adult: A case report (ASH 2025) - "He received five sessions of plasma exchange (PLEX) and pulse methylprednisolone followed by a slow prednisone taper. Inpatient eculizumab was not available; outpatient infusion was arranged... This case underscores the importance of recognizing influenza-triggered complement-mediated atypical hemolytic uremic syndrome (aHUS) and concurrent influenza myocarditis with conduction disease. Early PLEX, immunosuppression, and timely complement inhibition, even if initiated after discharge, are critical."

Case report • Clinical • Atypical Hemolytic Uremic Syndrome • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Cough • Hematological Disorders • Infectious Disease • Inflammation • Influenza • Nephrology • Respiratory Diseases • Thrombocytopenic Purpura

Atypical HUS: Diagnostic challenge and therapeutic success with eculizumab (ASH 2025) - "She was treated with intravenous fluids and started on antibiotics with ceftriaxone and metronidazole for diverticulitis. Differentiating aHUS from TTP and STM-HUS is critical, as management strategies differ significantly. Prompt initiation of eculizumab can reverse renal injury and prevent further organ damage."

Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Complement-mediated Rare Disorders • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Nephrology • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • HP

Thrombotic thrombocytopenic purpura with features of evans syndrome in a case of lupus vasculitis (ASH 2025) - "Introduction: Thrombotic thrombocytopenic purpura (TTP), distinguished by severe ADAMTS13 deficiency, is an emergency requiring immediate plasma exchange (PLEX). SLE patients with concurrent Evans syndrome and acquired TTP present a diagnostic and therapeutic challenge. Early testing for ADAMTS-13 activity and initiating PLEX in a timely fashion is of utmost importance. Such patients often need combined immunomodulation with steroids and rituximab, targeting the underlying shared B-cell pathology."

Clinical • Acute Kidney Injury • Antibody-mediated Rejection • Atypical Hemolytic Uremic Syndrome • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Glomerulonephritis • Hematological Disorders • Hypertension • Immune Thrombocytopenic Purpura • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Musculoskeletal Pain • Nephrology • Pulmonary Disease • Renal Disease • Systemic Lupus Erythematosus • Thrombocytopenia • Thrombocytopenic Purpura • Vasculitis • HP

A single center review of secondary hemophagocytic lymphohistiocytosis treatment and outcomes. (ASH 2025) - "Initial therapy was malignancy-specific chemotherapy (39%), HLH-94 protocol based therapy (30%), steroids alone (23%), and anakinra (2%) while others were not treated (6%)...Overall, 46% of patients required several lines of treatment and were subsequently treated with several additional agents in the second line setting including malignancy directed therapy, ruxolitinib, alemtuzumab, eculizumab, IVIG, cyclosporine, tacrolimus and rituximab...To improve timely diagnosis and treatment decisions, we, like other centers, are implementing electronic medical record order sets for HLH diagnosis and management and organizing an HLH expert panel to provide timely case reviews and treatment recommendations. In memory of our esteemed colleague and co-author Stephen Njau, MD"

Clinical • Review • Dyslipidemia • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hypertriglyceridemia • Immunology • Infectious Disease • Rare Diseases • Solid Tumor • IL2RA • ISG20

The use of eculizumab and tocilizumab in the treatment of hyperhemolysis syndrome, a literature review (ASH 2025) - "All patients received standard therapy of methylprednisolone and IVIG for a range of 1 to 5 days, except for case number 11 that received rituximab and eculizumab without steroids or IVIG. Emerging evidence from available case reports highlights promising outcomes with the use of tocilizumab and eculizumab in refractory cases of HHS. In addition, these agents offer an opportunity to further understand the underlying pathophysiology of HHS. However, the rarity of the disease poses significant challenges to research."

Review • Cardiovascular • Genetic Disorders • Hematological Disorders • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Sickle Cell Disease

Eculizumab for hyperhemolysis syndrome in sickle cell disease: A systematic review and meta-analysis (ASH 2025) - "Common pre-treatments included steroids (n = 9/14, 64%), intravenous immunoglobulins (IVIG) (n = 9/14, 64%), and Rituximab (n = 5/14, 36%). Conclusion Eculizumab was associated with the complete resolution of HHS in the majority of cases, with a low recurrence rate and an excellent survival rate at follow-up. However, there is a lack of high-quality data and larger, prospective registries and clinical trials are urgently needed to validate these findings, define optimal patient selection, timing, and dosing."

Retrospective data • Review • Cardiovascular • Genetic Disorders • Hematological Disorders • Hypotension • Infectious Disease • Sickle Cell Disease • Thrombosis

Rapidly progressive acute chest syndrome is associated with complement-mediated cell injury in adults with sickle cell disease (ASH 2025) - "Additional testing on a single sample by flow cytometry showed that C5b9 deposition was fully blocked by adding eculizumab but only partially blocked by danicopan, suggesting a contribution of the classical complement pathway as a driver. However, due to the small sample size, our results should be considered as hypothesis-generating. Future studies with larger cohorts and newer functional complement assays, like the mHAM 2.0, should be considered to obtain definitive results."

Clinical • Cough • Genetic Disorders • Hematological Disorders • Pulmonary Disease • Respiratory Diseases • Sickle Cell Disease • Thrombocytopenia • CD55 • CD59

Eculizumab vs control therapies in paroxysmal nocturnal hemoglobinuria: A meta-analysis of six randomized trials (ASH 2025) - "Across trials, eculizumab did not significantly reduce breakthrough hemolysis (RR 1.17; 95% CI: 0.64–2.13), and the risk of hemoglobin normalization was comparable between groups (RR 0.95; 95% CI: 0.85–1.05). Similarly, LDH normalization (RR 0.99; 95% CI: 0.90–1.09) and transfusion avoidance (RR 0.85; 95% CI: 0.66–1.11) did not show a statistically significant advantage for eculizumab. In terms of safety, rates of any AE (RR 0.98; 95% CI: 0.75–1.29), SAEs (RR 0.79; 95% CI: 0.53–1.17), drug withdrawal due to AEs (RR 0.96; 95% CI: 0.28–3.27), and mortality (RR 1.28; 95% CI: 0.34–4.83) were similar across groups."

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

A diagnostic pivot: Paroxysmal nocturnal hemoglobinuria mimicking refractory immune thrombocytopenia in an elderly woman with autoimmune comorbidities (ASH 2025) - "Case Description: An 82-year-old woman with a history of Sjögren's syndrome and autoimmune hypothyroidism presented with progressive fatigue, mucosal bleeding, and worsening thrombocytopenia (platelets 9 x 10⁹/L) unresponsive to corticosteroids, IVIG, and weekly romiplostim over two months...Complement inhibition with ravulizumab or eculizumab can transform the disease course by reducing hemolysis, thrombosis, and transfusion dependence. In conclusion, this case illustrates that classic hemolytic PNH may present as isolated thrombocytopenia in patients with autoimmune backgrounds. Early recognition and targeted therapy can significantly improve patient outcomes and quality of life, even in the elderly."

Clinical • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Endocrine Disorders • Fibrosis • Hematological Disorders • Hepatology • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Leukopenia • Meningococcal Infections • Myelodysplastic Syndrome • Paroxysmal Nocturnal Hemoglobinuria • Pneumococcal Infections • Rare Diseases • Sjogren's Syndrome • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis • CD55 • CD59 • HP

Complement inhibition in post-transplant IgA-mediated autoimmune cytopenia: A pediatric case report (ASH 2025) - "He developed cellular rejection one-year post-transplant and was treated with cyclosporine and MMF. At 7 years post-transplantation, he developed acute cellular rejection with third-degree heart block requiring pulse steroids and ATG, with subsequent transition to tacrolimus/sirolimus...Modification of immunosuppression is particularly challenging in the post solid organ transplant setting and can risk organ rejection requiring close collaboration with primary transplant team.⁵⁻⁶ In IgA-driven diseases like IgA nephropathy, complement inhibitors (e.g., eculizumab, narsoplimab) are gaining traction.⁷ This case adds to emerging evidence that complement modulation is a viable treatment pathway for refractory IgA-mediated AIHA, especially in the post-transplant setting. Eculizumab with prednisone was effective and well-tolerated in this case of IgA-mediated, rituximab-refractory AIHA post-heart transplant. Complement inhibition may represent a novel and safe therapeutic..."

Case report • Clinical • Post-transplantation • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Immunology • Pediatrics • Renal Disease • Solid Organ Transplantation • Thrombocytopenia • Transplantation

Direct comparison of crovalimab versus eculizumab in paroxysmal nocturnalhemoglobinuria: A systematic review and meta-analysis of randomized controlled trials (ASH 2025) - "Crovalimab offers comparable efficacy and safety to eculizumab in the treatment of PNH, both in C5-inhibitor–naive patients and those transitioning from prior therapy. With no rise in SAEs, crovalimab was linked to notable improvements in hemoglobin levels, fatigue scores, hemolysis control, and transfusion avoidance. Due to its subcutaneous mode of administration and long-lasting therapeutic benefit, crovalimab offers an adequate prospective alternative for conventional intravenous C5 inhibitors."

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

Early access program for danicopan (ALXN2040) as add-on treatment to eculizumab or ravulizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH): Preliminary data from the Italian real-world survey. (ASH 2025) - "Antithrombotic prophylaxis was reported in 4 patients (2warfarin and 2 low molecular weight heparin (LMWH)). to date, data from 10 of the treated patients are available (4 females, median age 41.5ys, range22-49, and 6 males, median age 58ys, range 33-86). Patients mainly suffered from classical PNH (80%),followed by PNH/aplastic anemia (PNH/AA, 20%). Median laboratory tests at the beginning of the C5iwere as follows: hemoglobin level (Hgb) 8.9 g/dl (range, 7.0-9.8), reticulocytes (Ret) count 180*10^6/L(range, 20-341), LDH value 5 x upper limit of normality (ULN) (range, 1.5-28)."

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

Correlation between efficacy, clonal dynamics evolution, and development of bone marrow failure in PNH/AA syndrome treated with complement inhibitors: A single-center cohort study (ASH 2025) - "Objective:To investigate the correlation between therapeutic response patterns to complement inhibitors, clonaldynamics changes, and progression of bone marrow failure (BMF) in patients with PNH/AA (paroxysmalnocturnal hemoglobinuria/aplastic anemia).A retrospective analysis was conducted on 92 PNH/AA patients treated at our center from 2021 to 2025.All patients received complement inhibitor therapy (eculizumab, crovalimab, or iptacopan), with a medianfollow-up of 29 months.Parameters monitored included PNH clone size, next-generation sequencing (NGS), lactatedehydrogenase (LDH) levels, hematologic response, breakthrough hemolysis (BTH), and dynamicchanges in hematopoietic function (reticulocytes, absolute neutrophil count, platelets). Complement inhibitors effectively control hemolysis in PNH/AA patients but provide limitedimprovement in BMF. Residual hemolysis, the emergence of new subclones, and an expanding PNH cloneare associated with BMF progression. Timely..."

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

Real-world data on breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria treated with proximal and terminal complement inhibitors. (ASH 2025) - "Four patients were treated with factor D inhibitor danicopan(n=3) or iptacopan (n=1) concurrently with ravulizumab.A total of 49 BTH events were identified; while on eculizumab (26 events, 12 patients), ravulizumab (14events, 7 patients), ravulizumab and danicopan (6 events, 3 patients), pegcetacoplan (1 event, 1 patient),zilucoplan (2 events, 2 patients), and no events while on iptacopan. Twelve BTH events were incidentally detected during routine CIadministration; more frequent lab draws may be beneficial for patients with chronic hemolysis. Moredata is needed to understand the BTH rates of different CIs and guide clinicians in BTH management."

Clinical • Real-world • Real-world evidence • Anemia • Aplastic Anemia • Breast Cancer • Complement-mediated Rare Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Solid Tumor • CD55 • CD59 • HP

Oral iptacopan monotherapy demonstrates clinically meaningful hemoglobin increases in patients with paroxysmal nocturnal hemoglobinuria with baseline hemoglobin levels 10 to <12 g/dl on anti-C5 therapy: Subgroup analysis of the appulse-pnh Phase 3b trial (ASH 2025) - P3 | "Iptacopan, the first oral selectivefactor B inhibitor, demonstrated superior efficacy vs anti-C5 therapy (eculizumab/ravulizumab) inpatients with PNH and Hb <10 g/dL on anti-C5 in APPLY-PNH (NCT04558918). In APPULSE-PNH, switching from anti-C5 to oral iptacopan monotherapy led to clinicallymeaningful increases in Hb in patients with PNH and Hb ≥10 g/dL. Results in patients with BL Hb 10 to<12 g/dL were consistent with the overall study findings. Iptacopan was well tolerated."

Clinical • Monotherapy • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Apply-PNH: Analysis of complement pathway biomarkers provides evidence for pharmacodynamic response in PNH patients who receive oral iptacopan monotherapy versus continuing anti-C5 therapy (ASH 2025) - P3 | "The Phase 3 APPLY-PNH trial (NCT04558918) evaluated iptacopan in adults with PNH and residual anemia(Hb <10 g/dL) despite ≥6 months of stable anti-C5 therapy (either eculizumab or ravulizumab), whichshowed superior efficacy of receiving iptacopan monotherapy over continuing anti-C5 therapy. Analysis of complement pathway biomarkers provides evidence for pharmacodynamicresponse and supports the clinical benefits of switching from anti-C5 therapy to iptacopan. sC5b-9decreased after receiving iptacopan, consistent with the observed clinical efficacy of iptacopan treatmentin the study through inhibition of the terminal complex activation of the complement pathway. FBincrease in the setting of iptacopan could be due to decreased consumption and/or increased productionof FB."

Biomarker • Clinical • Monotherapy • PK/PD data • Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Serum ferritin changes in iptacopan-treated patients with paroxysmal nocturnal hemoglobinuria (ASH 2025) - "Conversely, when IVH is controlled by terminal complement component 5(C5) inhibitors e.g. eculizumab, some patients remain anemic due to extravascular hemolysis (EVH), andthey may accumulate iron from frequent blood transfusions and/or increased intestinal iron absorption,which may lead to iron overload (IO). Treatment with iptacopan normalizes SF in anti-C5-naïve PNH patients with low SF byblocking IVH. In contrast to anti-C5 therapies, SF does not increase during iptacopan treatment in anti-C5-pretreated PNH patients, indicating that these patients no longer demonstrate EVH-related, persistentanemia, or require blood transfusions. Thus, by targeting IVH and EVH, iptacopan restores ironhomeostasis to a more physiological state, possibly preventing ID and IO in patients with PNH."

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