Fabhalta (iptacopan) / Novartis - LARVOL DELTA

Tumor-Derived Complement Factor B Drives Tumor Growth and Anti-PD-1 Resistance in STK11-Mutant Lung Adenocarcinoma (IASLC-WCLC 2025) - "These results identify tumor-derived C3 and CFB as a novel signaling axis to target in STK11-mutant LUAD and point to the potential role of the alternative complement pathway in tumor immune evasion. These results also provide rationale for an early phase clinical trial of CFB inhibitors such as Iptacopan to enhance anti-PD-1 effectiveness in patients with STK11 -mutant LUAD."

IO biomarker • Complement-mediated Rare Disorders • Hematological Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Solid Tumor • CD8 • CFB • KRAS • STK11

Optimizing Fabhalta Therapy: Strategies and Best Practices in PNH Patients (ICBMT 2025) - "Sponsored by Novartis"

Clinical

Severe hemolysis flare of refractory autoimmune hemolytic anemia with positive complement component C3d responsive to Iptacopan with cyclophosphamide and prednisone: a case report. (PubMed, Hematology) - "Three refractory cases of AIHA showed good therapeutic efficacy after treatment with iptacopan combined with cyclophosphamide and prednisone. These cases provide a potentially effective treatment option for severe hemolytic episodes in refractory AIHA."

Journal • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Successful treatment of transplant-associated thrombotic microangiopathy with iptacopan: a non-adult case study. (PubMed, Front Immunol) - "The patient exhibited significant improvements in laboratory markers, including reductions in lactate dehydrogenase, urine protein/creatinine ratio, and C5b-9 levels, along with recovery of platelet counts and haptoglobin levels. This case highlights the potential efficacy of iptacopan in the management of TA-TMA, particularly in high-risk patients, and suggests that complement factor B inhibition may offer a promising therapeutic strategy for this challenging condition."

Journal • Bone Marrow Transplantation • Hematological Disorders • Thrombocytopenia • Thrombosis • Transplantation • CFB • HP

Targeting the Alternative Complement Pathway by Iptacopan Abrogates C3 and Strongly Reduces C5b-9 Deposition within Glomeruli in IgA Nephropathy Recurrence after Kidney Transplantation. (PubMed, Am J Transplant) - "In addition, it demonstrates in vivo modulation of glomerular complement deposition, specifically preventing C3 deposition and C5b-9 fixation, which is considered a major effector mechanism of tissue injury. Large cohorts are required to define its impact on clinical outcomes in long-term transplant settings."

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease • Transplantation

Characterization of Breakthrough Hemolysis in Patients With Paroxysmal Nocturnal Hemoglobinuria: An International Multicenter Experience. (PubMed, Am J Hematol) - "BTH incidence was 0.19 events per patient-year, maximal with proximal inhibitors (0.4 events per patient-year), and lower for anti-C5 (0.18 per patient-year). By logistic regression analysis, the main predictors of BTH were more severe disease at diagnosis (increased LDH and a shorter time to first complement inhibitor), treatment with proximal inhibitors, and poorer EBMT response category."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Patient-Reported Meaningful Change in Symptoms and Impacts of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Three Phase III Clinical Trials of Iptacopan. (PubMed, Patient) - P3 | "Findings from these interviews provide valuable patient-reported data on the positive treatment experience and meaningful improvements in PNH symptoms and health-related quality-of-life impacts patients reported after receiving iptacopan. These qualitative reports from patients support and contextualize the positive efficacy results demonstrated in the three iptacopan clinical trials. NCT04558918 (16 Sep 2020), NCT04820530 (25 Mar 2021), NCT04747613 (09 Feb 2021)."

Journal • P3 data • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Successful targeting of the alternative complement cascade with iptacopan for the treatment of IgA nephropathy: a case report. (PubMed, Swiss Med Wkly) - "To the best of our knowledge, our case report is the first in Switzerland to show that selective inhibition of the alternative complement pathway in IgA nephropathy results in significant and ongoing reduction of proteinuria after six months of therapy, supporting the innovative concept of targeting the alternative complement pathway with iptacopan to treat IgA nephropathy."

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease • CFB

Case Report: Iptacopan in a paroxysmal nocturnal hemoglobinuria patient with severe renal insufficiency. (PubMed, Front Med (Lausanne)) - "After switching from eculizumab to iptacopan, the patient achieved transfusion independence, sustained hematologic improvement, and resolution of both intravascular and extravascular hemolysis. Iptacopan was well tolerated, with only mild adverse effects and no breakthrough hemolysis or infections. This case highlights the potential of iptacopan as a therapeutic option in PNH patients with severe renal impairment requiring dialysis."

Journal • Aplastic Anemia • Cardiovascular • Chronic Kidney Disease • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Thrombosis

What do clinical trials teach us about the pathophysiology of human IgA nephropathy? (PubMed, Nephrol Dial Transplant) - "Beyond systemic steroids, we now have targeted release formulation of budesonide which is thought to act primarily on the gut-associated lymphoid tissue, to reduce the production of pathogenic galactose-deficient IgA1...Recognizing the role of the alternative complement cascade in IgAN mediated glomerular injury and inflammation identified new potential therapeutic targets and ultimately led to the approval of complement Factor B inhibitor, iptacopan. Other non-immunosuppressive treatments are also available or being investigated with the aim of reducing proteinuria and slowing chronic kidney disease progression, including endothelin A receptor antagonists. In this paper, we review current clinical trials in IgAN and critically examine what they teach us about IgAN pathogenesis."

Journal • Chronic Kidney Disease • Cognitive Disorders • Glomerulonephritis • IgA Nephropathy • Inflammation • Lupus Nephritis • Nephrology • Renal Disease • CFB

PRIORITY- PNH: NIS PDC the Efficacy and Safety of Iptacopan in Adults in Routine Clinical Practice (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Severe hemolysis flare of refractory warm hemolytic anemia with positive complement component C3d responsive to Iptacopan with cyclophosphamide and prednisone (Frontiers) - "Refractory wAIHA shows poor responsiveness to multiple treatment regimens. In this report, we describe three refractory cases with positive complement component C3d and hemolysis flare. These patients were successfully treated with oral factor B inhibitor Iptacopan in conjunction with cyclophosphamide and prednisone. All three patients showed a rapid increase in Hb levels, a decrease in reticulocyte proportion, and significant reduction in hemolysis manifestations (Lower LDH level and unconjugated bilirubin). These cases provided a potentially effective treatment option for severe hemolysis episodes in refractory wAIHA."

Clinical • Autoimmune Hemolytic Anemia

Targeting the Roots of Kidney Disease: Systematic Review of the Therapies Targeting the Complement System. (PubMed, Medicina (Kaunas)) - "Meanwhile, avacopan, a C5a receptor antagonist, addresses ANCA-associated vasculitis (AAV) by mitigating inflammation and enabling reduced reliance on corticosteroids. Similarly, narsoplimab, which inhibits MASP-2, targets the lectin pathway implicated in conditions such as aHUS. Iptacopan, a factor B inhibitor, focuses on the alternative pathway and demonstrates efficacy in managing C3 glomerulopathy (C3G). A systematic review of complement-targeted therapies was conducted, analysing studies from 2013 to 2023 that address unmet medical needs in primary and secondary glomerular diseases. Our systematic review of complement-targeted therapies shows that these tailored and innovative treatments may specifically address unmet medical needs in primary and secondary glomerular diseases."

Journal • Review • ANCA Vasculitis • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Inflammation • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Vasculitis

Recurrent C3 Glomerulonephropathy in a Kidney Transplant Recipient Treated with Iptacopan (WTC 2025) - "Treatment with mycophenolate mofetil, lisinopril, dapagliflozin and furosemide, led to improved UPCR of 2.18 mg/mg. Our case demonstrates efficacy of Iptacopan in proteinuria reduction and decrease in kidney disease progression as demonstrated by stable Scr levels."

Clinical • Complement-mediated Rare Disorders • Fibrosis • Glomerulonephritis • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Meningococcal Infections • Nephrology • Renal Disease • Transplantation

Recurrent C3 Glomerulonephritis (C3GN) in Kidney Transplant Recipients: A Case Highlighting the Role of Iptacopan (WTC 2025) - "Several therapies, including plasma exchange, intravenous immunoglobulin (IVIG), rituximab, and complement pathway inhibitors such as eculizumab, have been explored for recurrent C3GN, but their efficacy remains variable and is often limited by cost, access, or side effects. This case underscores the challenges of recurrent C3GN in transplant recipients and highlights iptacopans potential efficacy in stabilizing disease progression. While this patient's response was encouraging, further studies are needed to evaluate the long-term safety, efficacy, and optimal use of iptacopan and other complement-targeting therapies in transplant patients with C3GN."

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis • Inflammation • Lupus Nephritis • Nephrology • Transplantation • CFB

Safety of Drugs in Breastfeeding Women With CKD. (PubMed, Kidney Int Rep) - "Among renin-angiotensin system inhibitors, enalapril and captopril are safe for breastfeeding. Based on limited evidence, quinapril, benazepril, candesartan, and valsartan are likely acceptable for use during breastfeeding. We found no compelling human data regarding the safety of other renin-angiotensin system inhibitors or sodium-glucose cotransporter type 2 (SGLT2) inhibitors, finerenone, sparsentan, or glucagon-like peptide-1 receptor agonists (GLP1RAs) in lactation. Immunosuppressive agents, including azathioprine, cyclosporine, tacrolimus, budesonide, rituximab, and eculizumab are acceptable for use during breastfeeding. Belimumab is most likely safe; however, data are limited...No studies were found on the safety of breastfeeding while on the newer complement inhibitors, including avacopan, ravulizumab, iptacopan, and pegcetacoplan...Human lactation data on the safety of most drugs used in the treatment of CKD are limited, making evidence-based recommendations..."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Enhanced immunocompatibility and hemocompatibility of nanomedicines across multiple species using complement pathway inhibitors. (PubMed, Sci Adv) - "However, both iptacopan and danicopan display poor efficacy with PEGylated liposomal doxorubicin. Sutimlimab, an inhibitor of the classical pathway, demonstrates poor efficacy with PEGylated liposomal doxorubicin, even in sera with anti-PEG antibodies...Iptacopan also alleviates nanoparticle-induced lethargy in rats and severe hypotension in dogs. These data suggest that complement inhibitors can enhance the immunocompatibility and hemocompatibility of nanomedicines in a donor-dependent manner."

Journal • Hypotension • Inflammation

Study to Evaluate the Impact of Iptacopan on Top of SOC on Biopsy Changes in Kidneys of Adult Patients With IgAN (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease

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

Efficacy and safety of agents for IgA nephropathy: a network meta-analysis of randomized controlled trials. (PubMed, Front Med (Lausanne)) - "Clinical remission (26 RCTs included in the analysis): The CR for tonsillectomy combined with steroids pulse therapy (TSP) (RR = 8.23, 95% CI 4.11-16.45), anti-APRIL monoclonal antibody sibeprenlimab (RR = 10.00, 1.34-74.48), and steroids combined with renin-angiotensin system inhibitors (STE + RASI) (RR = 5.03, 2.61-9.68) were significantly superior to placebo. Proteinuria control (36 studies assessing 24-h UPE): The BLyS/APRIL dual-target inhibitor telitacicept (SMD = -5.21, -7.55 to -2.87) and STE + RASI (SMD = -1.98, -3.15 to -0.82) significantly reduced 24-h UPE, outperforming the mycophenolate mofetil combined with steroids regimen (SMD = -0.97, -2.74 to 0.80)...Safety (36 studies reporting adverse events): The complement inhibitor iptacopan (88.4%) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) (85.4%) had the lowest incidence of adverse events, significantly better than immunosuppressive regimens...Telitacicept, sparsentan, and TSP can be considered as..."

Journal • Retrospective data • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

A Masked, Placebo-controlled Study to Assess Iptacopan in Age-related Macular Degeneration (clinicaltrials.gov) - P2 | N=170 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

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

CLINICAL FEATURES AND OUTCOMES OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS TREATED WITH ECULIZUMAB IN TAIWAN: A MULTICENTER RETROSPECTIVE ANALYSIS (EHA 2025) - "Prior treatments included steroids (29.4%), cyclosporine (18.9%), anti-thymocyte globulin (10.8%), danazol (24.2%), and one crovalimab trial participant...Adjuvant therapies for EVH associated with symptomatic anemia included rituximab (n=2), steroids (n=14), cyclosporine (n=6), and danazol (n=5)... Eculizumab effectively reduces intravascular hemolysis and improves survival in Taiwanese PNH patients, though BTH and transfusion-dependent treatment discontinuation remain challenges."

Retrospective data • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Pulmonary Disease • Rare Diseases • Renal Disease • Thrombosis

PRIORITY- PNH: NIS PDC the Efficacy and Safety of Iptacopan in Adults in Routine Clinical Practice (clinicaltrials.gov) - P=N/A | N=100 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New trial • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

A PHASE 1, RANDOMIZED, PARTICIPANT- AND INVESTIGATOR-BLINDED, PLACEBO-CONTROLLED STUDY TO EXPLORE THE SAFETY AND PHARMACOKINETICS OF SUPRATHERAPEUTIC MULTIPLE DOSES OF IPTACOPAN IN HEALTHY VOLUNTEERS (EHA 2025) - "Supratherapeutic multiple oral doses of 400- and 800-mg iptacopan were well tolerated. These supratherapeutic doses of iptacopan showed rapid absorption, low to moderate PK variability and dose proportional exposure. Considering T1/2 variability, the elimination of iptacopan was similar across the supratherapeutic doses."

Clinical • P1 data • PK/PD data • Back Pain • Complement-mediated Rare Disorders • Dyspepsia • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Musculoskeletal Pain • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease