Fabhalta (iptacopan) / Novartis - LARVOL DELTA

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

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

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

Efficacy of iptacopan in treatment of transplant-associated thrombotic microangiopathy (TA-TMA) post-allogeneic hematopoietic stem cell transplantation: A case series analysis (ASH 2025) - "Case III (28M, MDS-LB) . Baseline Characteristics Diagnosis Severe Aplastic Anemia (SAA) Myelodysplastic Syndrome with Excess Blasts-2 (MDS-EB-2) Myelodysplastic Syndrome-Low Blast (MDS-LB) Pre-Treatment Labs - WBC: ↓ (2.13×10⁹/L) - HGB: 65g/L↓ - PLT: 4×10⁹/L↓↓ - ALT/AST: ↑ (44.56/50.96 U/L) - WBC: ↓ (3.73×10⁹/L) - HGB: 44g/L↓↓ - PLT: 19×10⁹/L↓ - PT/INR: ↑ (24.8s/2.17) - WBC: ↑ (15.42×10⁹/L) - HGB: 105g/L↓ - ALT/AST: ↑ (35.49/47.32 U/L) - D-dimer: 3.56 mg/L↑ Complications CMV viremia, TA-TMA, intestinal GVHD, heart failure EBV infection, TA-TMA, intestinal GVHD EBV viremia, liver GVHD, intestinal GVHD, TA-TMA New Drugs Used Iptacopan, Vedolizumab Iptacopan Iptacopan, Vedolizumab, Ruxolitinib Post-Treatment Trends Blood Routine - WBC/HGB/PLT: Continued fluctuations (no stabilization) - PLT: ↑ (improvement) - WBC/HGB: Partial stabilization - WBC: Stabilized - HGB/PLT: Gradual improvement Liver Function - ALT/AST: Persistent fluctuations..."

Clinical • Aplastic Anemia • Bone Marrow Transplantation • Cardiovascular • Congestive Heart Failure • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Heart Failure • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Myelodysplastic Syndrome • Transplantation

Efficacy and safety of iptacopan in paroxysmal nocturnal hemoglobinuria (PNH): A real-world study of 35 patients from anhui, China (ASH 2025) - "All received iptacopan (200 mg twice daily), with 12 patients also taking cyclosporine and 8 receiving testosterone undecanoate...Safety profile: Mild rash occurred in 6 patients (17.1%), all on concurrent prednisone; symptoms resolved after stopping prednisone, with no recurrence on iptacopan monotherapy...Responses are particularly robust in classical PNH and younger patients, while those with BMF may benefit from early combination therapy. Its favorable safety profile supports long-term use, offering valuable insights for individualized PNH management, particularly in Asian populations."

Clinical • Real-world • Real-world evidence • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • CD59 • CFB

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

The 2-year efficacy and safety of iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria with a history of aplastic anemia on concomitant immunosuppressive therapy who entered the roll-over extension program (ASH 2025) - P3 | "This subgroup analysis of patients from APPLY-PNH (NCT04558918) andAPPOINT-PNH (NCT04820530) who entered PNH-REP included patients with a history of AA receivingconcomitant IST (cyclosporine); patients with severe AA were excluded from the studies based onlaboratory parameters. In this subgroup analysis of PNH patients with AA+IST, long-term treatment with iptacopanmaintained clinically meaningful improvements in Hb levels, reduced transfusion needs, and sustainedcontrol of hemolysis over 2 years, with safety outcomes comparable to patients without AA. Thesefindings support the durable efficacy and safety of iptacopan in this population."

Clinical • Monotherapy • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

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

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

The role of red blood cell lifespan in evaluating the condition of patients with paroxysmal nocturnal hemoglobinuria treated with complement inhibitors (ASH 2025) - "Four patients were treated with Eculizumab: 1 achieved CR, 2achieved PR, and 1 achieved minimal partial remission (MIPR).Following treatment, the median LDH level decreased by 1689 U/L (820–3114.6), and all patients had LDHlevels below twice the upper limit of normal (ULN) within three weeks, with 20 maintaining this level.Median RBC lifespan increased by 30.5 days (-16–71), with the following changes by treatment group:Crovalimab: -3.5 days (-16–3); Iptacopan: +61 days (24–71); KP104 cohort 1: +37 days (26–62); KP104cohort 2: +53 days (31–60); Eculizumab: -2 days (-7–12). Different complement inhibitors, whether targeting upstream or downstream components ofthe complement system, demonstrate varying effects on PNH disease control. Hemoglobin levels duringtreatment are an independent factor influencing therapeutic outcomes, and RBC lifespan is closelyassociated with hemoglobin dynamics. RBC lifespan provides a quantitative measure of extravascularhemolysis and serves as..."

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

Efficacy and safety of iptacopan in Chinese patients with paroxysmal nocturnal hemoglobinuria: A multicenter retrospective study (ASH 2025) - "Treatmentregimens included iptacopan monotherapy (200 mg bid) in 25% (5/20) and combination therapy(cyclosporine n=3, prednisone n=1) in 20% (4/20). These real-world data demonstrate iptacopan's rapid efficacy in improving hematologic parameters,relieving fatigue, and achieving durable transfusion independence with favorable safety in PNH, thoughlarger prospective studies are needed for validation. Further validation through extended follow-up andlarger-scale studies is warranted."

Retrospective data • Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • CD55 • CD59

The improvement of renal function by complement inhibitors in patients with paroxysmal nocturnal hemoglobinuria (ASH 2025) - "Both eculizumab and iptacopan have been shown to improve renal function in patients with PNH."

Clinical • Chronic Kidney Disease • Complement-mediated Rare Disorders • Hematological Disorders • Inflammation • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease

Impact of iptacopan, a complement inhibitor, on Chinese patients with paroxysmal nocturnal hemoglobinuria: A multicenter retrospective cohort study (ASH 2025) - "(Bravo-Perez, 2023) Currently, complement inhibitors such as eculizumab and iptacopan arestandard treatments; while eculizumab effectively inhibits C5 activation, it does not fully controlintravascular hemolysis. At Week 4, 11 patients were evaluable, and hemoglobin levels rose by an average of 27 g/L (95%CI: 5.72 to 49.00) from baseline, with no red blood cell transfusions required. Remarkably, 2 patients(18%; 95% CI: 2.3 to 51.8) achieved hemoglobin normalization, defined as having at least one hemoglobinlevel ≥12 g/dL during follow-up without transfusions. By the 2-month mark, 10 evaluable patients wereassessed, showing a mean hemoglobin increase of 33 g/L (95% CI: 10.02 to 55.98) and no transfusionneeds."

Retrospective data • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Thrombosis • CD55 • CD59

Severe hemolysis flare of refractory warm hemolytic anemia with positive complement component C3d responsive to iptacopan with cyclophosphamide and prednisone (ASH 2025) - "All patients had received at least two prior therapies, including but not limited to steroids,IVIG, rituximab, tacrolimus and azathioprine without achieving a good response...In addition, twopatients (13.33%) had a history of bortezomib treatment, and another two patients (13.33%) hadreceived azathioprine therapy... Refractory wAIHA patients achieved good therapeutic efficacy after treatment with Iptacopancombined with cyclophosphamide and prednisone. Our clinical practice will provide a new potentialapproach to the treatment of refractory wAIHA."

Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Systemic Lupus Erythematosus

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

Maternal and fetal pharmacokinetics (PK) of pegcetacoplan in paroxysmal nocturnal hemoglobinuria (PNH): A case report of use in pregnancy (ASH 2025) - "Aftertrials of vemircopan and iptacopan, she was transitioned to pegcetacoplan 1080 mg subcutaneous2x/week and achieved transfusion independence (hemoglobin ~110 g/L)...Thesefindings are consistent with preclinical non-human animal data and pegcetacoplan's physicochemicalproperties—a large, pegylated, and hydrophilic cyclic peptide, expected to have limited membranepermeability.In a patient with hemolytic PNH and inadequate hematologic response to eculizumab, conception onpegcetacoplan was not associated with adverse fetal/pregnancy outcomes, and third-trimesterreinitiation resulted in rapid hematologic improvement, transfusion independence, and anuncomplicated peripartum course.In conclusion, this report provides the first clinical and PK evidence suggesting that third-trimester use ofpegcetacoplan may be a viable treatment option in select pregnant patients with PNH with suboptimalresponse to C5 inhibitors. Following reinitiation of pegcetacoplan at 28 weeks GA,..."

Case report • Clinical • PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Diabetes • Genetic Disorders • Gestational Diabetes • Obesity • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Long-term safety and efficacy of iptacopan in patients with paroxysmal nocturnal hemoglobinuria: 4- and 5-year follow-up of patients from Phase 2 studies who entered the roll-over extension program (ASH 2025) - P2, P3 | "These long-term data show that initial improvement in Hb levels with iptacopan is retainedover time, with most patients keeping normal Hb levels at their latest follow-up. This hematologicimprovement was associated with transfusion independence, as well as with LDH <1.5×ULN, and ARCnormalization in most patients, confirming the comprehensive, long-term control of intravascular andextravascular hemolysis with iptacopan. Despite the increased proportion of PNH erythrocytes, BTH andMAVEs remain rare."

Clinical • P2 data • Cardiovascular • Complement-mediated Rare Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease • Paroxysmal Nocturnal Hemoglobinuria • Pneumococcal Infections • Pneumonia • Rare Diseases • Respiratory Diseases • Septic Shock

The effect of breakthrough hemolysis on complement factor h and factor I levels in paroxysmal nocturnal hemoglobinuria (ASH 2025) - "Patients were grouped according to CI at sampling; untreated [n=16],eculizumab [n=10], ravulizumab [n=15], pegcetacoplan [n=16], iptacopan [n=15]). CFI is dependent on the presence of cofactors, such as CFH, to regulatecomplement which may explain why upstream CFH levels and not CFI levels rise in BTH. These findingssupport the concept that dynamic changes in CFH may play an active role in the acute regulation ofcomplement during BTH."

Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • CD55 • CD59

Access to innovative treatment for paroxysmal nocturnal hemoglobinuria in low- and middle-income countries (ASH 2025) - "The Introduction of iptacopan through the Humanitarian PACT represents a critical steptoward addressing inequities in access to PNH treatment in LMICs. Strategic implementation planningenables country partners to integrate novel therapies into existing health systems while building capacityin diagnostics and clinical management. By addressing both access and system readiness, this modeldemonstrates how equitable access to innovative medicines may serve as a foundation for strengtheningrare disease care in resource-limited settings."

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

Oral iptacopan demonstrates efficacy as salvage therapy for high-risk transplant-associated thrombotic microangiopathy: First real-world experience (ASH 2025) - "Recent advances in complement inhibition have demonstrated promising therapeutic potential, asevidenced by eculizumab (Jodele S, et al...Elevated urinary protein excretion (rUPCR ≥1 mg/mg) and elevated sC5b-9level were present in 10 and 13 patients, respectively.The treatment before iptacopan included calcineurin inhibitor withdrawal (n=18), plasma exchange (n=7),defibrotide administration (n=4), anti-CD20 therapy (n=11), and anti-C5 therapy (n=9)... The oral complement inhibitor iptacopan demonstrated significant clinical efficacy as salvage therapy inhigh-risk TA-TMA patients, particularly when administered as second-line therapy, with infections beingthe most common adverse events. These findings support further prospective evaluation of iptacopan asa targeted therapy for TA-TMA."

Clinical • Real-world • Real-world evidence • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Infectious Disease • Meningococcal Infections • Transplantation • CFB

Navigating the complement cascade: A multicenter journey from pegcetacoplan to iptacopan in paroxysmal nocturnal hemoglobinuria (ASH 2025) - "This first multicenter real-world analysis demonstrates that the pegcetacoplan-to-iptacopantransition provides clinical benefit in the majority of this initial set of patients with PNH, with significantimprovements in hemoglobin and an excellent safety profile while maintaining clone stability. The highacceptance rate suggests that patients prefer oral therapy over subcutaneous administration. Thesefindings address a critical knowledge gap in proximal complement inhibitor sequencing, suggesting thatiptacopan is an effective therapeutic option for patients with inadequate pegcetacoplan response andsupporting the development of evidence-based treatment algorithms for optimal PNH care in the era ofmultiple complement inhibitor options."

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