Fabhalta (iptacopan) / Novartis - LARVOL DELTA

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

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

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

OBTAINING INSIGHTS ON PNH MANAGEMENT WITH IPTACOPAN IN EVERYDAY CLINICAL PRACTICE: A RESEARCH COLLABORATION WITH THE IPIG PNH REGISTRY (EHA 2025) - P | "It compares favorably to other complement inhibitors (CI) like eculizumab and ravulizumab. This research collaboration is advancing research and innovation in PNH. Recruiting patients for PNH studies is challenging due to its rarity. The IPIG PNH Registry supports collaborative efforts to gather real-world data on patient outcomes and treatment efficacy."

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

EFFECTIVENESS AND SAFETY OF IPTACOPAN IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS WITH PERSISTENT ANEMIA AFTER C5 INHIBITION: THE REAL-WORLD EXPERIENCE OF THE FRENCH EARLY ACCESS PROGRAM (EHA 2025) - "This first analysis of French EAP shows that treatment with iptacopan in real-world permits a reduction of RBCT requirements with a significant increase in Hb levels within the first 15 days of treatment. There were no discontinuations and no new safety signals. The next analysis by the end of 2025 will provide additional long-term and quality of life results for a better understanding of iptacopan's safety and effectiveness in real-world patients with ."

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

APPULSE-PNH: ORAL IPTACOPAN MONOTHERAPY DEMONSTRATES CLINICALLY MEANINGFUL HEMOGLOBIN (HB) INCREASES IN PATIENTS (PTS) WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) AND HB ≥10 G/DL ON ANTI-C5 THERAPY (EHA 2025) - P3 | "Iptacopan, the first oral selective factor B inhibitor, had superior efficacy vs anti-C5 (eculizumab/ravulizumab) in pts with PNH and Hb <10 g/dL on anti-C5 in APPLY-PNH (NCT04558918). APPULSE-PNH met its primary and key secondary objectives. Oral iptacopan monotherapy led to clinically meaningful increases in Hb, Hb normalization in almost all pts, transfusion avoidance in all pts and reductions in ARC. Pts also reported improvements in fatigue and treatment satisfaction."

Clinical • Monotherapy • CNS Disorders • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Pain • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases

Real-world iptacopan use among United States patients with paroxysmal nocturnal hemoglobinuria (ISTH 2025) - "The median (IQR) MPR and PDC were 98% (90–103%) and 95% (88–98%), respectively. Table or Figure Upload"

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

EFFICACY OF COMPLEMENT INHIBITORS AND HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A META ANALYSIS AND SYSTEMATIC REVIEW (EHA 2025) - "Among the patients receiving treatment, the transfusion avoidance rate of the Eculizumab group was 84% (95% CI: [78%, 89%]), vs Ravulizumab group was 46% (95% CI: [0%, 98%]),vs Pegetacoplan was 88% (95% CI: [79%, 93%]), and Iptacopan continued to show significant efficacy, with a transfusion avoidance rate of 95% (95% CI: [88%, 100%]). As the first-line treatment option, complement inhibitors has positive effect for PNH, allogeneic HSCT is an effective treatment option for patients with invalid or inaccessible complement inhibitors."

Retrospective data • Review • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Transplantation

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

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

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

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

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

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

THE 2-YEAR SAFETY AND EFFICACY OF IPTACOPAN MONOTHERAPY IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) FROM APPLY- AND APPOINT-PNH STUDIES WHO ENTERED THE ROLL-OVER EXTENSION PROGRAM (REP) (EHA 2025) - P3 | "The 2-year data showed that iptacopan was well tolerated with no new safety signals and no increase in exposure-adjusted rates of AEs or SAEs with longer treatment duration. Sustained Hb ≥ 12 g/dL and LDH <1.5 x ULN in majority of pts at 2-year reflect comprehensive hemolysis control with iptacopan, accompanied by improvement in patient-reported fatigue. These findings continue to support oral iptacopan monotherapy as a potentially practice-changing treatment for pts with PNH."

Clinical • Monotherapy • Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Respiratory Diseases

PNH-NIS: A Multi-center, Ambispective Cohort Study to Evaluate the Impact of Iptacopan for Adult Patients With PNH in China (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

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

Novartis Fabhalta shows statistically significant and clinically meaningful improvements in hemoglobin in new population of patients with PNH (Novartis Press Release) - P3b | N=52 | APPULSE (NCT05630001) | Sponsor: Novartis Pharmaceuticals | "Novartis announced positive results from APPULSE-PNH, a Phase IIIB study evaluating the efficacy and safety of twice-daily oral monotherapy Fabhalta (iptacopan) in adult patients with paroxysmal nocturnal hemoglobinuria (PNH) with Hb levels ≥10g/dL who switched from anti-C5 therapies (eculizumab or ravulizumab). After 24 weeks of treatment with Fabhalta, the Hb level improved on average by 2.01 g/dL (95% CI, 1.74, 2.29) with most patients achieving normal or near-normal levels 1. Data will be presented at the European Hematology Association (EHA) Congress 2025....No patients required transfusion during the study, and the vast majority (92.7%) achieved Hb ≥12g/dL, reaching normal or near-normal levels."

P3 data • Paroxysmal Nocturnal Hemoglobinuria

Successful Management of C3 Glomerulopathy Recurrence Post-Kidney Transplantation with Iptacopan: A Case Report. (PubMed, Int J Mol Sci) - "The direct control of the complement dysregulation underlying the pathogenesis of C3G with Iptacopan was accompanied by improvements in clinical, laboratory and histological features, with demonstrated reduced disease activity and slowed disease progression. Therefore, the case report described is intended to shed light on the potential role of new AP complement blockers in the treatment of C3G."

Journal • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Rare Diseases • Renal Disease • Transplantation

Online Education Improved Nephrologists' Knowledge of The Immunopathogenesis of Immunoglobulin A Nephropathy and Rationale for Novel Therapies (ERA 2025) - "Nephrologists significantly improved their knowledge of the immunopathogenesis of IgAN (58% correct responses at baseline rising to 74% post-activity; P <.001), and the MOA of the emerging IgAN therapy iptacopan acting via the alternative complement pathways (73% vs 85% post-activity; P <.01). There was a numerical improvement in knowledge of the MOA of the APRIL (proliferation-inducing ligand) inhibitor sibeprenlimab acting via reduction of circulating levels of galactose-deficient IgA1 (Gd-IgA1) and associated immune complexes (48% vs 56% post- activity; P =.070)... This online activity significantly improved nephrologists' knowledge of the immunopathogenesis of IgAN and the rationale and MOA of some emerging therapies for IgAN. Given the rapidly evolving treatment landscape for IgAN, nephrologists would benefit from additional education to improve their knowledge of emerging therapies and translate this knowledge into clinical practice and improved patient..."

Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease

A multicenter, randomized, double-blind, placebo-controlled Phase 3 study in patients with idiopathic IC-MPGN: APPARENT protocol amendment (ERA 2025) - P3 | "This study will provide evidence towards the efficacy and safety of iptacopan in idiopathic IC-MPGN in adult and adolescent patients. Figure1: Study Design *Participants will switch to open-label treatment of iptacopan after Day 180 visit if they meet inadequate response criteria and will complete the 360 days double-blind period before transitioning to 180 days open-label period"

Clinical • P3 data • Cardiovascular • Fibrosis • Glomerulonephritis • Immunology • Infectious Disease • Lupus Nephritis • Monoclonal Gammopathy • Solid Organ Transplantation

Iptacopan's rapid and sustained inhibition of overactive complement alternative pathway in C3G: Exploratory analysis from the Phase 3 APPEAR-C3G study (ERA 2025) - P3 | "Biomarker results from the APPEAR-C3G study confirmed inhibition of the AP with iptacopan, demonstrated by a rapid onset and sustained improvement of serum C3, along with a reduction in AP activity and terminal complement complex sC5b-9 over a 12-month period. Results were also replicated in the placebo arm after switch to open label iptacopan."

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

Effect of iptacopan discontinuation on proteinuria and complement biomarkers in patients with immunoglobulin A nephropathy (IgAN): a post hoc analysis from a Phase II trial (ERA 2025) - P3 | "The data indicate that iptacopan discontinuation leads to quick reactivation of systemic and renal complement to near BL levels. Renal complement reactivation is associated with an increase in proteinuria. Notably, proteinuria decreased again after reinitiation of iptacopan, indicating continued sensitivity to complement inhibition."

Biomarker • Clinical • P2 data • Retrospective data • Glomerulonephritis • IgA Nephropathy • Inflammation • Renal Disease • CFB