Fabhalta (iptacopan) / Novartis - LARVOL DELTA

New Novartis data at ASCO and EHA showcase momentum of pioneering portfolio with promising pipeline (Novartis Press Release) - "Fabhalta APPULSE-PNH full results build on Phase III program, reporting new data from expanded PNH population in adults switching from anti-C5; Ianalumab Phase II data in immune thrombocytopenia..."

Clinical data • Paroxysmal Nocturnal Hemoglobinuria • Thrombocytopenia

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

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

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

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

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

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

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

Post-authorization Safety Study of Iptacopan in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Using Data From the IPIG PNH Registry (clinicaltrials.gov) - P=N/A | N=200 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Active, not recruiting

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

Alternative Complement Pathway, Iptacopan, and IgA Nephropathy. (PubMed, N Engl J Med) - No abstract available

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

Alternative Complement Pathway, Iptacopan, and IgA Nephropathy. (PubMed, N Engl J Med) - No abstract available

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

Alternative Complement Pathway, Iptacopan, and IgA Nephropathy. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

Iptacopan's rapid and sustained inhibition of overactive complement alternative pathway in C3G: Exploratory analysis from the Phase 3 APPEAR-C3G study (ERA 2025) - No abstract available

P3 data • Chronic Kidney Disease

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) - No abstract available

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

Predicting long-term benefits of improvements in estimated glomerular filtration rate (eGFR) with iptacopan on delaying kidney failure in Complement 3 Glomerulopathy (C3G) (ERA 2025) - No abstract available

Glomerulonephritis • Renal Disease

Long-term stabilization of kidney function (estimated glomerular filtration rate) with iptacopan in patients with native C3 glomerulopathy (ERA 2025) - No abstract available

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis

Reduction of hematuria and albuminuria with iptacopan in C3G: Findings from APPEAR-C3G study (ERA 2025) - No abstract available

Renal Disease

Real-world evidence for efficacy and safety of Iptacopan and Pegcetacoplan in patients with primary membranoproliferative glomerulonephritis (MPGN) (ERA 2025) - No abstract available

Clinical • HEOR • Real-world • Real-world evidence • Glomerulonephritis • Lupus Nephritis • Nephrology

Evaluation of C3 deposition in patients with C3G: insights from the APPEAR-C3G Phase 3 study in patients treated with iptacopan (ERA 2025) - No abstract available

Clinical • P3 data • Renal Disease

Real-world experience of Iptacopan in C3 Glomerulopathy (ERA 2025) - No abstract available

Clinical • Real-world • Real-world evidence • Complement-mediated Rare Disorders • Glomerulonephritis

A mechanistic biopsy study of the effect of iptacopan on immunopathology in patients with IgA nephropathy (IgAN) (ERA 2025) - No abstract available

Biopsy • Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Advancements in Complement Inhibition for PNH and Primary Complement Mediated Thrombotic Microangiopathy. (PubMed, Blood Adv) - "These agents currently include pegcetacoplan, a C3 inhibitor, iptacopan, an oral factor B inhibitor, danicopan, an oral factor D inhibitor, and crovalimab, an anti-C5 monoclonal antibody. In addition, we review current data supporting the use of these novel agents for aHUS, for which only the terminal complement inhibitors eculizumab and ravulizumab are currently approved. Future research is crucial to establish the long-term efficacy and safety profiles of these novel therapies, ensuring the best treatment strategies for patients with PNH and aHUS."

Journal • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases