Fabhalta (iptacopan) / Novartis - LARVOL DELTA

The Complement System: An Important New Therapeutic Target in IgA Nephropathy. (PubMed, Glomerular Dis) - "Iptacopan recently received accelerated approval for the indication and complement inhibitory drugs will likely become an integral part of the treatment for this disease in the near future. As these drugs become available in the clinic, it will be important to develop biomarkers that can guide clinicians to the best drug for an individual patient."

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

Iptacopan for cold agglutinin disease: a case report with literature review. (PubMed, Front Immunol) - "This study reports a case of cold agglutinin disease (CAD) secondary to lymphoplasmacytic lymphoma in a patient intolerant to rituximab plus bendamustine and with persistent uncontrolled hemolysis following zanubrutinib therapy. The addition of the complement C3 inhibitor iptacopan to a cyclophosphamide and dexamethasone regimen successfully controlled hemolysis and improved hemoglobin levels...The follow-up period was 4 months, during which the patient showed sustained remission. These findings suggest that iptacopan can rapidly ameliorate hemolysis in CAD, warranting further investigation into its therapeutic potential."

Journal • Review • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

Pegcetacoplan Subcutaneous Infusion: Early Access and Patient Training (KIDNEY WEEK 2025) - "Often treated with corticosteroid and mycophenolate with variable success, oral complement inhibitor, iptacopan, has been approved for C3G therapy. There were no reported difficulties or adverse events related to the SCI administration or adverse effects with pegcetacoplan Conclusion Patients can safely self-administered SCI infusions of pegcetacoplan with minimal training. One in-person training session was sufficient to make patients competent in self-administration and remote training was also successfully used."

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease

Real-world evidence for efficacy and safety of Iptacopan and Pegcetacoplan in patients with primary membranoproliferative glomerulonephritis (MPGN) (ESPN 2025) - "Preceding therapies included steroid pulses (n = 13 patients), oral prednisone (n = 23), MMF (n = 25), calcineurin inhibitors (n = 3) and RAS inhibitors (n = 27). Our real-world findings confirm impressive antiproteinuric efficacy and potentially GFR stabilizing effects of PCI in patients with limited response to conventional treatments, with a favorable safety profile."

Clinical • HEOR • Real-world • Real-world evidence • Complement-mediated Rare Disorders • Glomerulonephritis • Infectious Disease • Lupus Nephritis • Nephrology • Pediatrics • Pneumonia • Renal Disease • Respiratory Diseases

Advancing Clinical Readiness for C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis: Outcomes from a CME-Based Educational Intervention (KIDNEY WEEK 2025) - "Background The standard of care for rare kidney diseases such as complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) is evolving rapidly, driven by the recent FDA approval of iptacopan for C3G and promising late-phase study data for pegcetacoplan. As the availability and experience with newer CIs increase, future studies will further inform us about changes in treatment patterns and strategies. [The CME education was supported by an unrestricted educational grant from Apellis Pharmaceuticals]"

Clinical • CME • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Pediatrics • Renal Disease

Progress in the use of biological therapies to treat paroxysmal nocturnal hemoglobinuria: focus on patient profiling. (PubMed, Expert Opin Biol Ther) - "While eculizumab, the first anti-C5 antibody, reduced intravascular hemolysis (IVH) and thrombotic risk, it required fortnightly infusions and left a significant percentage of patients with persistent anemia. New terminal complement inhibitors, such as long-acting ravulizumab and subcutaneous crovalimab, have allowed for better control of IVH and demonstrated efficacy in patients with specific C5 genetic polymorphisms (crovalimab). Proximal complement inhibitors, including the small molecule pegcetacoplan (C3 inhibitor), the recently approved orally administered iptacopan (factor B inhibitor), and danicopan (factor D inhibitor, in combination with anti-C5), efficiently control C3-mediated extravascular hemolysis...PNH specialists must now balance multiple factors beyond efficacy alone. Disease characteristics such as previous thrombotic events or transfusion needs, as well as drug administration routes, patient preferences toward oral or parenteral administration and..."

Journal • Review • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Clinical Efficacy of Pegcetacoplan vs. Iptacopan in Patients with C3 Glomerulopathy: Indirect Treatment Comparisons (KIDNEY WEEK 2025) - P3 | "Conclusion These two ITCs indicate that pegcetacoplan was superior to iptacopan in lowering proteinuria levels and achieving the composite renal endpoint in patients with C3G. The findings from this analysis may help guide clinicians managing patients with this rare condition."

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Renal Disease

Reduction of hematuria and albuminuria with iptacopan in C3 glomerulopathy: findings from APPEAR C3 glomerulopathy study (ESPN 2025) - "The results demonstrate that iptacopan effectively reduces the levels of active disease biomarkers such as hematuria and albuminuria associated with C3G which was sustained over 12 months of treatment. Beneficial effects were observed in patients receiving placebo after switching to iptacopan treatment. These data continue to support iptacopan as an important treatment option that targets the root cause of C3G."

Complement-mediated Rare Disorders • Glomerulonephritis • Renal Disease

A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY IN PATIENTS WITH IDIOPATHIC IC-MPGN: APPARENT PROTOCOL AMENDMENT (ESPN 2025) - P3 | "This study will provide evidence towards the efficacy and safety of iptacopan in idiopathic IC-MPGN in adult and adolescent patients."

Clinical • P3 data • Cardiovascular • Glomerulonephritis • Renal Disease

LONG-TERM STABILIZATION OF KIDNEY FUNCTION (ESTIMATED GLOMERULAR FILTRATION RATE) IN PATIENTS WITH NATIVE C3 GLOMERULOPATHY (ESPN 2025) - P2, P3 | "In patients with native C3G, iptacopan 200 mg bid resulted in the stabilization of eGFR trajectory, with significant change observed in patients with at least mild renal impairment at baseline (<90 mL/min/1.73 m2) and maintenance of stable eGFR in those with normal baseline eGFR (≥90 mL/min/1.73 m2). eGFR slope analysis has demonstrated valuable utility in monitoring kidney function over time, and these data suggest iptacopan treatment results in a long-term, clinically relevant positive impact on kidney function."

Clinical • Chronic Kidney Disease • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease

Potent Bispecific Antibody Inhibiting Activation of Complement Alternative Pathway and Lectin Pathway for lgAN Therapy (KIDNEY WEEK 2025) - "Iptacopan, an oral inhibitor targeting Factor B(CFB) to inhibit complement alternative pathway (AP) has secured FDA approval, and several complement lectin pathway (LP) inhibitors are also currently undergoing clinical trials for IgAN...Furthermore, the selected PCC candidate present favorable pharmacokinetics and safety profiles, supporting the potential as a first-in-class therapy for IgAN and other glomerulonephritide diseases. IND-enabling studies are conducted."

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

Iptacopan Treatment in Patients with C3 Glomerulopathy (C3G): 12-Month Results from the Early Access Program (KIDNEY WEEK 2025) - "After 12 months of iptacopan treatment, the eGFR slope was -4.7 mL/min/1.73m 2 /year (change in slope +6.0 mL/min/1.73m 2 /year; 95% CI: -8.8, 20.7; p=0.411) in native patients and -0.1 mL/min/1.73m 2 /year (change in slope +22.9 mL/min/1.73m 2 /year; 95% CI: 11.2, 34.6; p=0.001) in recurrent patients ( Figure ). Conclusion In the early access program, 12 months of iptacopan treatment resulted in slowing of disease progression in native and recurrent patients with C3G."

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Renal Disease

IgAN with Extracapillary Proliferation in Genetically Identical Twins: Use of Iptacopan (KIDNEY WEEK 2025) - "Despite treatment with corticosteroids, rituximab, and cyclophosphamide, he progressed to end-stage renal disease, requiring dialysis and transplantation...Despite receiving corticosteroids, cyclophosphamide, and azathioprine, eGFR declined to 82 mL/min/1.73 m2, with UPCR 1 g/g and microhematuria. Azathioprine was switched to mycophenolate, and enteric budesonide and dapagliflozin were added...Histologic diagnosis is essential to guide treatment based on disease pathogenesis. The favorable response to Iptacopan supports inhibition of the complement pathway as a promising strategy in management of IgAN with crescentic and C3 deposits"

Cardiovascular • Fibrosis • Glomerulonephritis • Hypertension • IgA Nephropathy • Immunology • Lupus Nephritis • Nephrology • Pulmonary Disease • Renal Disease

More than Skin Deep: Successful Management of Rare IgA Vasculitis with Kidney Involvement (KIDNEY WEEK 2025) - "Diagnosed with IgAV with IgA dominant glomerulonephritis, she was started on prednisone, mycophenolate mofetil (MMF), and lisinopril. RAAS blockade, corticosteroids and cyclophosphamide or MMF are mainstay of treatment, but newer drugs like sparsentan and iptacopan, specifically targeting the immune system, have shown promise. From left to right: Gross specimen minimal interstitial fibrosis, IF granular mesangial IgA deposition, LM IgA-dominant mesangial deposits with mesangial hypercellularity and crescent."

Fatigue • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Lupus Nephritis • Musculoskeletal Pain • Nephrology • Renal Disease • Vasculitis

Early Insights into Characteristics and Treatment Patterns of US Patients (Pts) with IgAN Who Were Prescribed Iptacopan: The APPRISE-IgAN Data Platform (KIDNEY WEEK 2025) - "Conclusion This interim analysis highlights characteristics and treatment patterns of pts with IgAN receiving iptacopan. Recruitment for APPRISE-IgAN and collection of data for additional pts, clinical outcomes, and longer follow-up times are ongoing and will provide further valuable insights on this pt population over time."

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Baseline Characteristics and Treatment Satisfaction of Patients (Pts) Enrolled in C3 Glomerulopathy (C3G) Connect: Interim Results from a Home-Reported Outcomes (HROs) Study (KIDNEY WEEK 2025) - "The most common treatments included mycophenolate (25%), iptacopan (17%), and furosemide (17%). Conclusion In this small initial sample of pts with C3G, tracked symptoms and treatment satisfaction varied, and fatigue was the most frequently tracked symptom at baseline. This heterogeneity highlights a need to understand the diverse perspectives and symptom burden of pts with C3G, and how app-based tracking of HROs can capture these individualized experiences and supplement pt-reported outcomes."

Clinical • Complement-mediated Rare Disorders • Fatigue • Glomerulonephritis • Nephrology • Renal Disease

Update to the Long-Term Efficacy and Safety of Iptacopan in C3 Glomerulopathy: 39-Month Phase 2 Extension Study Data (KIDNEY WEEK 2025) - P3 | "A stable eGFR was maintained in a majority of recurrent C3G patients. Iptacopan was well tolerated with a favorable safety profile in both cohorts."

Clinical • P2 data • Complement-mediated Rare Disorders • Glomerulonephritis • Rare Diseases • Renal Disease

Clinical Variability and Outcomes in C3 Glomerulopathy: A Single-Center Experience (KIDNEY WEEK 2025) - "Case 4 underwent partial remission and was offered a clinical trial with investigational drug Iptacopan, which showed evident benefit in proteinuria reduction and stabilization of eGFR...Case 2 progressed rapidly to ESKD despite immunosuppression, while Case 3 showed a relapsing-remitting course with steroid resistance. Case 4 showed partial remission following participation in a clinical trial, underscoring the potential role of emerging therapies in C3G management."

Clinical • Complement-mediated Rare Disorders • Fibrosis • Glomerulonephritis • Immunology • Lupus Nephritis • Nephrology • Rare Diseases • Renal Disease

Successful Iptacopan Treatment of a Patient with C3 Glomerulopathy (C3G) (KIDNEY WEEK 2025) - "From this point-of view, the current case report , shows that iptacopan is highly effective regarding the reduction of proteinuria and recovery and stabilization of kidney function and is well tolerated. Our case report suggests that even under the 6-month monotherapy, iptacopan may become a promising oral treatment option for C3G."

Clinical • Anemia • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Infectious Disease • Influenza • Lupus Nephritis • Meningococcal Infections • Nephrology • Pneumococcal Infections • Renal Disease • Respiratory Diseases

Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: C3G Extension Trial Interim Results from the Phase 3 APPEAR-C3G Patients (KIDNEY WEEK 2025) - P3 | "Conclusion Iptacopan demonstrated sustained reduction in proteinuria and stabilization of eGFR slope with treatment up to 24 months among APPEAR-C3G pts who rolled over to the long-term extension study. Iptacopan was well tolerated with a favorable safety profile in C3G pts."

Clinical • P3 data • P3 data: top line • Complement-mediated Rare Disorders • Glomerulonephritis • Renal Disease

Real-World Treatment for IgAN in the Veterans Health Administration (KIDNEY WEEK 2025) - "IgAN treatments, including systemic glucocorticoids (SGC), other immunosuppressants (azathioprine, mycophenolate, or cyclophosphamide), angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and novel treatments (iptacopan, sparsentan, targeted delayed-release budesonide) were ascertained using pharmacy records and categorized as continued use at IgAN diagnosis, incident use at IgAN diagnosis, discontinued use after IgAN diagnosis, or no use...Conclusion Low rates of existing and novel treatment use in this cohort reveal an opportunity to improve adherence to draft updates to IgAN guidelines that suggest using immunomodulating agents concurrently with supportive therapies such as ACEi/ARBs and SGLT2is. Many people discontinued treatments, suggesting a possible role for novel therapies as alternative options."

Clinical • HEOR • Real-world • Real-world evidence • Ankylosing Spondylitis • Chronic Kidney Disease • Dermatitis • Dermatology • Glomerulonephritis • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • IgA Nephropathy • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Renal Disease • Rheumatology • Seronegative Spondyloarthropathies

Efficacy and Safety of Iptacopan in Patients (Pts) from East Asia with IgAN: Interim Results from the Phase 3 APPLAUSE-IgAN Trial (KIDNEY WEEK 2025) - P3 | "TEAEs led to treatment discontinuation in 1.1% of pts on iptacopan and 2.2% on pbo. Conclusion The efficacy and safety of iptacopan was consistent between pts from East Asia and the overall main study population in the APPLAUSE-IgAN IA."

Clinical • P3 data • P3 data: top line • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • CFB

Randomized, Controlled Phase 2 Study to Evaluate Iptacopan Treatment in Patients with Active ANCA-Associated Vasculitis (KIDNEY WEEK 2025) - P2 | "This Phase 2 study randomizes patients in a placebo-controlled 24-week (W) induction period to evaluate the efficacy and safety of iptacopan (200mg twice daily) in combination with rituximab induction therapy and rapid defined GC tapering, for treatment of newly diagnosed or relapsed adult patients with active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Figure 1. Iptacopan in patients with ANCA-associated vasculitis – Phase 2 trial design"

Clinical • P2 data • ANCA Vasculitis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Rare Diseases • Vasculitis

Biomarker Insights from the Phase 3 APPLAUSE-IgAN Study: Iptacopan's Proteomic Signature in IgAN (KIDNEY WEEK 2025) - P2, P3 | "Conclusion These data expand iptacopan’s previously reported Phase II proteomic signature and suggest that alternative complement pathway inhibition downregulates several IgAN-related biological processes. Biomarker analyses to be conducted at completion of APPLAUSE-IgAN and an ongoing kidney biopsy study (NCT06797518) will help to further characterize mechanistic aspects of alternative complement pathway inhibition in IgAN."

Biomarker • P3 data • Glomerulonephritis • IgA Nephropathy • Inflammation • Renal Disease • CFB

Novartis Fabhalta (iptacopan) meets Phase III primary endpoint, slows kidney function decline in patients with IgA nephropathy (IgAN) (Novartis Press Release) - "Fabhalta, an oral alternative complement pathway inhibitor, demonstrated statistically significant, clinically meaningful superiority compared to placebo in slowing IgAN progression measured by annualized total slope of estimated glomerular filtration rate (eGFR) decline over two years....data support 2026 submission for traditional FDA approval."

FDA filing • P3 data • IgA Nephropathy