Ultomiris (ravulizumab-cwvz) / AstraZeneca, Xencor - 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

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

Long-term therapy with eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria: Two-year interim results of a prospective multicenter observational study (ASH 2025) - "Introduction: The complement C5-inhibition with eculizumab or ravulizumab is a current standard of care in patients with paroxysmal nocturnal hemoglobinuria (PNH)...The prospective multicenter observational study ECU-PNH-N02 was initiated to evaluate the results of long-term therapy with a biosimilar of eculizumab (Elizaria®) in a Russian cohort of patients with PNH in accordance with national treatment protocols... Thus, the results of the study indicate a long-term stable course of PNH during safe and effective treatment with a biosimilar of eculizumab. Acknowledgments: The authors thank all the investigators and patients who participated and continues to participate in this study."

Clinical • Observational data • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases

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

Beyond the assays: Managing unresolvable TMA and the pharmacokinetic cost of plasma exchange (ASH 2025) - "Case presentation: A 73-year-old man with history of Tetralogy of Fallot with bioprosthetic aortic valve replacement on warfarin and CKD stage IIIb (baseline creatinine 1.7–1.8 mg/dL) presented with two weeks of progressive jaundice, anorexia, and fatigue...Under the suspicion of complement-mediated Hemolytic Uremic Syndrome (HUS), PLEX was held, meningococcal vaccination administered, and penicillin V prophylaxis initiated...PLEX was resumed followed by Rituximab infusion and a 7-day steroid taper...A second dose of Ravulizumab was administered two weeks after the initial dose, at which point PLEX was discontinued...Therefore, beyond emphasizing pre-PLEX sampling to avoid dilutional false negatives, this case highlights the need for rapid, discriminatory biomarkers and protocols that reconcile the competing demands of urgent PLEX and sustained complement inhibition. Finally, elderly patients with limited reserve may sustain permanent organ damage even with optimal..."

PK/PD data • Anorexia • Atypical Hemolytic Uremic Syndrome • Chronic Kidney Disease • Gastroenterology • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Meningococcal Infections • Nephrology

The use of danicopan as an add-on therapy in a ravulizumab-treated adult patient with paroxysmal nocturnal hemoglobinuria (PNH) and concomitant stage IV renal failure has induced a marked improvement of anemia and of clinically significant extravascular hemolysis in absence of deterioration of renal function (ASH 2025) - "In 2019, this patient was treated with biosimilar eculizumab (phase 3 trial- ABP959-Amgen) till spring 2022. In conclusion, danicopan has demonstrated high efficacy in increasing hemoglobin level (range 2.3-3 g/dL), and reducing markers of hemolysis in a PNH patient with concomitant stage IV renal failure, having an inadequate hematological response to either eculizumab or ravulizumab (hemoglobin <9•5 g/dL). Interestingly, renal function was not affected by the combined use of ravulizumab and danicopan, during a 11 months- follow-up observation period."

Clinical • Metastases • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Endocrine Disorders • Hematological Disorders • Hypertension • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • 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

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

Paroxysmal nocturnal hemoglobinuria in pediatric patients: A UK experience (ASH 2025) - "Approved treatments for those under 18 years of age include eculizumab (andbiosimilars), ravulizumab and latterly crovalimab (over 12 years)...One additional patient had a myelodysplasia diagnosis.Treatment of aplastic anemia in the 53 patients included no treatment for 9/53 (17%), anti-thymocyteglobulin and ciclosporin in 18/53 (34%), ciclosporin 1/53 (2%), oxymethalone 1/53 (2%) and hematopoieticstem cell transplant (HSCT) for 24/53 (45%) (either first or second line).Five thrombotic events occurred in 4 patients at diagnosis: 2 cerebral vein thromboses, 1 Budd Chiari and1 pulmonary embolism (PE) and portal vein thrombosis.Management of patients with PNH requiring complement inhibition (41/65):The majority of patients experienced at least 2 symptoms from PNH (30/41), including fatigue (26/41),thrombosis (2/41), abdominal pain (5/41), shortness of breath (7/41), hemoglobinuria (7/41), dysphagia(1/41), bruising/bleeding (18/41) and anemia (27/41)...Currently the PNH..."

Clinical • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Cardiovascular • Complement-mediated Rare Disorders • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Meningococcal Infections • Myelodysplastic Syndrome • Paroxysmal Nocturnal Hemoglobinuria • Pediatrics • Pulmonary Embolism • Rare Diseases • Respiratory Diseases

Study design of A phase 3, open-label trial for pozelimab and cemdisiran combination therapy in patients with paroxysmal nocturnal hemoglobinuria with inadequate control of intravascular hemolysis (ASH 2025) - "Treatment for PNH includes C5 inhibitorssuch as eculizumab/biosimilar, ravulizumab, and crovalimab, however, patients under terminalcomplement inhibition can experience residual intravascular hemolysis due to incomplete C5 blockade.The combination of pozelimab (a monoclonal antibody that prevents activation of C5) and cemdisiran (asilencing RNA that reduces production of circulating C5) is a novel approach being investigated for itsability to achieve durable inhibition of the terminal complement pathway. During the ext period, the secondary endpoints willinclude percent change in LDH from baseline to ext week 24 and ext week 52, normalization of LDH ateach visit through ext week 52, inclusive, and adequate control of hemolysis at each visit through extweek 52. Recruitment for this study is expected to begin around November 2025."

Clinical • Combination therapy • P3 data • Bone Marrow Transplantation • 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

Factor bb as a biomarker during breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria (ASH 2025) - "Patients were grouped according to CI at sampling; untreated [n=16],eculizumab [n=8], ravulizumab [n=21], pegcetacoplan [n=16], iptacopan [n=16]). Its consistent rise during BTH, followed by return tobaseline within days, supports its use as a sensitive biomarker. This may help assess ongoing BTHseverity and guide clinical decisions."

Biomarker • Complement-mediated Rare Disorders • Hepatology • Liver Failure • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Real-world analysis of ravulizumab safety and effectiveness in advanced age patients with paroxysmal nocturnal hemoglobinuria: Insights from the international PNH registry (ASH 2025) - P | "Ravulizumab (RAV), a second-generation complement C5 inhibitor (C5i) derived from eculizumab (ECU), is the current standard of carefor patients (pts) with PNH, where available. RAV demonstrated effective control of PNH activity in C5i-naive and ECU-experienced pts inthe real-world setting, regardless of age at initiation. LDH control and transfusion outcomes improved inboth age groups, with no significant differences observed. Despite a greater proportion of pts aged ≥65 yhaving a history of MAVEs and TEs, the incidence of these complications during treatment was low."

Clinical • Metastases • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Complement-mediated Rare Disorders • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Meningococcal Infections • Myelodysplastic Syndrome • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Cell Carcinoma • Septic Shock • Solid Tumor

Pegcetacoplan for patients with transplant-associated thrombotic microangiopathy treatment: A real-world report of six cases (ASH 2025) - "This cohort included one patient refractory to plasmaexchange and another who had failed both eculizumab and ravulizumab. This case series provides the first real-world evidence suggesting that proximal C3 inhibitionwith pegcetacoplan may be an effective and safe therapeutic option for pediatric TA-TMA. Treatment wasassociated with rapid and complete remissions, including in patients refractory to C5 inhibitors and otherconventional therapies. These encouraging findings support the investigation of pegcetacoplan inprospective clinical trials to formally establish its role in the management of this severe HSCTcomplication."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Immunology • Infectious Disease • Leukemia • Nephrology • Primary Immunodeficiency • Sickle Cell Disease • Transplantation

Outcomes in pediatric patients with HSCT-TMA treated with ravulizumab (ASH 2025) - P3 | "In this single-arm study, children diagnosed with HSCT-TMA and treated with rav for 26weeks were observed to have complete and partial TMA responses alongside a clinically meaningful OS of87.2%. Further posthoc analyses will be performed in subgroups of participants."

Clinical • Bone Marrow Transplantation • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pediatrics • Renal Disease • Respiratory Diseases • Thrombocytopenia

Danicopan add-on therapy demonstrates positive efficacy and safety outcomes in advanced age adults with paroxysmal nocturnal hemoglobinuria and clinically significant extravascular hemolysis: A sub-analysis of the phase 3 ALPHA trial (ASH 2025) - P3 | "During 12 weeks ofdanicopan add-on therapy, these patients reported meaningful improvements in Hb concentration andARC, while maintaining transfusion avoidance and a low rate of AEs. Overall, this analysis supports theuse of danicopan add-on therapy in patients with advanced age with PNH and csEVH treated withravulizumab or eculizumab, with no new safety signals."

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

Safety of ravulizumab use in pregnancy: Insights from a global pharmacovigilance analysis (ASH 2025) - P | "This analysis provides real-world insights on the use of ravulizumab in pregnancy andsuggests no unexpected safety signals, similar to analyses on the use of eculizumab duringpregnancy. These findings may inform clinical decision-making. As additional data are needed, a globalobservational study (NCT06312644) evaluating the safety of ravulizumab during pregnancy is currentlyongoing."

Adverse events • Clinical • Anemia • Aplastic Anemia • Atypical Hemolytic Uremic Syndrome • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Diabetes • Gestational Diabetes • Hepatology • Hypertension • Immunology • Metabolic Disorders • Myasthenia Gravis • Nephrology • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Real-world breakthrough hemolysis patterns across 1,723 patient-years of complement inhibition in paroxysmal nocturnal hemoglobinuria (ASH 2025) - "Clinical BTH episodes were more common in non-responders than responders in eculizumab(OR 2.32; p = .003), ravulizumab (OR 2.32; p = .a044), iptacopan (OR 10; p = 0.18) and pegcetacoplan (OR2.5; p = 0.21). These findings support prospective multicenter validation and thatiptacopan could maintain long-term disease stability. Current complement sequencing analysis is ongoingto classify patients with hemolysis."

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

Iptacopan monotherapy demonstrated improved clinical outcomes in a real-world cohort with paroxysmal nocturnal hemoglobinuria: Evidence from a managed access program (ASH 2025) - "The proportion of pts previously treated witheculizumab, ravulizumab, pegcetacoplan, and danicopan was 71.6%, 37.9%, 13.7%, and 6.3%,respectively. The updated data from this MAP confirm hematological and clinical improvements withiptacopan in Ci-naive and Ci-experienced pts with PNH, with approximately 6 months of iptacopantherapy. Oral iptacopan monotherapy led to normalization of Hb and LDH level, and RLC, along with ahigher proportion of pts achieving transfusion avoidance at retreatment visits compared to BL. Pts alsoreported notable improvements in fatigue and tx satisfaction."

Clinical • Clinical data • Monotherapy • Real-world • Real-world evidence • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • CFB