Fabhalta (iptacopan) / Novartis - LARVOL DELTA

Quantifying Spillover Impacts: Effect of Novel Therapies for IgA Nephropathy on Patients Awaiting Kidney Transplant (ISPOR 2025) - "IgAN interventions included therapies with FDA approval or phase 3 proteinuria reduction results (targeted-release budesonide, sparsentan, iptacopan, dapagliflozin, and atrasentan) in addition to nonspecific IgAN therapies (including renin-angiotensin-aldosterone system inhibitors and systemic corticosteroids); the comparator was nonspecific IgAN therapies alone. IgAN interventions may provide health benefits beyond the direct clinical benefits to affected patients. These additional societal benefits should be considered when conducting value assessment of novel IgAN treatments."

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

Horizon Scanning for Paroxysmal Nocturnal Hemoglobinuria in Brazil: Insights on Past Trends and Future Prospects (ISPOR 2025) - "Reimbursement decisions were obtained from the Conitec website in Brazil, and the reimbursement status in the UK for drugs not yet approved in Brazil was verified on the NICE website. We identified 10 treatments for PNH, six of which had FDA approval: eculizumab (2007, intravenous C5 inhibitor), ravulizumab (2018, intravenous C5 inhibitor), pegcetacoplan (2021, subcutaneous C5 inhibitor), iptacopan (2023, oral factor B inhibitor), danicopan (2024, oral factor D inhibitor used with eculizumab or ravulizumab), and crovalimab (2024, intravenous/subcutaneous C5 inhibitor). Recent cooperation between ANVISA and the FDA promises to accelerate drug approvals in Brazil. Three new therapies, including an oral monotherapy currently under ANVISA evaluation, could significantly improve pharmaceutical services by enhancing distribution and addressing geographical disparities."

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

Choosing the Right "Target" in IgA Nephropathy: A Case Series (NKF-SCM 2025) - "It is characterized by a high first-pass metabolism, making it preferable to prednisone due to its reduced systemic side effects. New treatments, such as oral iptacopan (complement pathway inhibitor) and sparsentan (endothelin antagonist), reduce IgAN disease activity via different mechanisms than TRF-budesonide. Further data and research are needed to help clinicians choose the ideal targets for their IgAN patient."

Clinical • Acne Vulgaris • CNS Disorders • Glomerulonephritis • Hypertension • IgA Nephropathy • Insomnia • Nephrology • Renal Disease • Sleep Disorder

The treatment of autoimmune hemolytic anemia with complement inhibitor iptacopan: a case report. (PubMed, Front Med (Lausanne)) - "The hemoglobin levels remained within a safe range after stopping the blood transfusion. It is reported as follows."

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

Novartis receives third FDA approval for oral Fabhalta (iptacopan) - the first and only treatment approved in C3 glomerulopathy (C3G) (PRNewswire) - "Novartis today announced that oral Fabhalta (iptacopan) has received U.S. Food and Drug Administration (FDA) approval for the treatment of adults with C3 glomerulopathy (C3G), to reduce proteinuria, making it the first and only treatment approved for this condition....The pivotal Phase III APPEAR-C3G study evaluated the efficacy and safety of twice-daily oral Fabhalta in adult patients with C3G. The study was comprised of a 6-month randomized, double-blind treatment period with Fabhalta compared to placebo in addition to supportive care, followed by an additional 6-month open-label treatment period where all participants received Fabhalta."

FDA approval • Complement-mediated Rare Disorders • Renal Disease

Design of A Patient (pt) Platform for Real-World Data (RWD) on Iptacopan and/or Atrasentan in the United StatEs (APPRISE) for Pts With Immunoglobulin A Nephropathy (IgAN) and Complement 3 Glomerulopathy (C3G) (NKF-SCM 2025) - P3 | "Recruitment of pts with IgAN began after iptacopan approval in 2024 and will expand with future approvals. The study period will extend from treatment initiation for the first pt to end of follow-up for the last pt.Results Analyses, including of clinical characteristics and treatment patterns, adherence, and effectiveness, will be conducted continuously and refined as sample sizes become sufficient.Conclusion APPRISE will enable rapid collection of varied RWD from pts prescribed iptacopan and/or atrasentan to overcome limitations of existing RWD sources, characterize real-world disease progression and treatment patterns, and support future studies to provide valuable insights into IgAN and C3G outcomes."

Clinical • Real-world • Real-world evidence • Glomerulonephritis • IgA Nephropathy • Renal Disease

A mechanistic biopsy study to evaluate structural and functional changes in kidneys of patients with IgA nephropathy (IgAN) receiving iptacopan on top of supportive care (NKF-SCM 2025) - "Other objectives will evaluate changes in biomarkers related to the AP, kidney function and structure, and disease progression from baseline to 9 months.Conclusion This study will explore iptacopan's impact on IgAN immunopathology by assessing glomerular complement activation together with renal histopathology, kidney function, and key biomarkers. The findings will enhance understanding of iptacopan's mechanistic effects on IgAN and potential kidney-protective benefits."

Biopsy • Clinical • Glomerulonephritis • IgA Nephropathy • Inflammation • Renal Disease • CFB

The Rapidly Changing Treatment Landscape of IgA Nephropathy. (PubMed, Semin Nephrol) - "This has directly resulted in the approval of three novel therapies specifically for the treatment of IgAN (nefecon, sparsentan, and iptacopan), and several others are in the late stages of clinical development. In this review, we outline the rationale for new therapies in development for IgAN and emerging clinical trial data and propose a new paradigm for the treatment of this condition."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Renal Disease

Efficacy and Safety of Iptacopan in Patients with Generalized Myasthenia Gravis: Study Design (AAN 2025) - P3 | "This study will investigate the efficacy and safety of iptacopan versus placebo in adult patients with AChR+ gMG."

Clinical • CNS Disorders • Immunology • Infectious Disease • Myasthenia Gravis

Drug reimbursement panel approves iptacopan for PNH reimbursement, rejects danicopan over cost concerns (Korea Biomedical Review) - "The Pharmaceutical Reimbursement Review Committee (PREC) has made mixed decisions on the two drugs for paroxysmal nocturnal hemoglobinuria (PNH): Fabhalta (iptacopan) and Voydeya (danicopan). On Thursday, the Health Insurance Review and Assessment Service (HIRA) announced the results of this year’s third PREC meeting."

Reimbursement • Paroxysmal Nocturnal Hemoglobinuria

First Oral PNH Treatment 'Fabhalta' Surpasses 8th Ridge of Reimbursement [Google translation] (Medipana) - "Paroxysmal nocturnal hemoglobinuria (PNH) treatment 'Fabhalta (iptacopan)' by Novartis Korea is one step closer to being listed for health insurance benefits...Thrombocytopenia treatment drugs 'Tavalis (fostamatinib)' by JW Pharmaceutical and 'Doptelet (avatrombopag)' by Handok have also received conditional benefits...On the 6th, the Health Insurance Review & Assessment Service held the 3rd Pharmaceutical Benefit Evaluation Committee in 2025 and disclosed the results of the review of the treatment benefits of the drugs for which decisions were submitted...Accordingly, after the drug price negotiation with the National Health Insurance Service (within 60 days), the upper limit (insurance drug price) will be set, and after the Ministry of Health and Welfare’s Health Policy Deliberation Committee announces the drug price announcement, it will be listed for reimbursement."

Reimbursement • Paroxysmal Nocturnal Hemoglobinuria • Thrombocytopenia

Urine complement analysis implies complement activation is involved in membranous nephropathy. (PubMed, Front Med (Lausanne)) - "The factor B inhibitor LNP023 and the factor D inhibitor BCX9930 are undergoing clinical trials for the treatment of MN. Our study indicates that complement abnormalities could serve as clinical biomarkers for tracking the progression of MN, predicting clinical remission, and guiding targeted complement therapy for those affected."

Journal • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Renal Disease • CD59

Novartis oral Fabhalta (iptacopan) receives positive CHMP opinion for the treatment of adults living with C3 glomerulopathy (C3G) (GlobeNewswire) - "Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion and recommended granting a marketing authorization for Fabhalta (iptacopan) – a first-in-class oral Factor B inhibitor of the alternative complement pathway – for the treatment of adults with C3 glomerulopathy (C3G)...The CHMP’s opinion is based on robust data from APPEAR-C3G, the first randomized, placebo-controlled Phase III study in C3G...Following the CHMP’s recommendation to approve Fabhalta for the treatment of adults with C3G, the European Commission (EC) will make a final decision within two months."

CHMP • EMA approval • Complement-mediated Rare Disorders • Rare Diseases • Renal Disease

A Multicenter Prospective Study of Iptacopan in the Treatment of Refractory/Relapsed Autoimmune Hemolytic Anemia (AIHA) (clinicaltrials.gov) - P=N/A | N=20 | Not yet recruiting | Sponsor: Bing Han

New trial • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy. (PubMed, Kidney Int Rep) - "In cohorts A + B combined, the median difference in C3 deposit score on renal biopsy from baseline was -7.00 (CI: -12.00 to 4.00;) at 9 to 12 months treatment with iptacopan. These data provide a clinical rationale for further evaluation of long-term treatment of C3G with iptacopan."

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

The road ahead: emerging therapies for primary IgA nephropathy. (PubMed, Front Nephrol) - "Sparsentan is indicated for persisting proteinuria...To reduce Gd-IgA1 production, targeted-release budesonide is approved...The terminal pathway inhibitors cemdisiran and ravulizumab show promise in phase 2 studies. Our current approach for those requiring immunosuppression involves combining the reduction of Gd-IgA1 (nefecon) with suppressing the effects of inflammation (iptacopan). The optimal duration of such therapy is uncertain. Clearly, there is more to be learned with many trials underway."

Journal • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Inflammation • Nephrology • Renal Disease

Oral iptacopan for paroxysmal nocturnal haemoglobinuria-First real-world experience. (PubMed, Br J Haematol) - No abstract available

Journal • Real-world evidence • Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria

Novartis receives Health Canada approval for Fabhalta oral treatment for adult patients with PNH (Canada Newswire) - "Novartis Canada is pleased to announce that Health Canada has granted a Notice of Compliance for Fabhalta (iptacopan capsules) as the first oral monotherapy treatment for adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who have hemolytic anemia. In clinical trials, treatment with Fabhalta offered superior hemoglobin improvement in the absence of red blood cell (RBC) transfusions...The Health Canada approval is based on the Phase III APPLY-PNH trial in patients with residual anemia despite prior anti-C5 treatment who switched to Fabhalta and supported by the Phase III APPOINT-PNH study in complement inhibitor-naïve patients."

Canada approval • Paroxysmal Nocturnal Hemoglobinuria

Examining Consistency Across NICE Single Technology Appraisals: A Review of Appraisals for Paroxysmal Nocturnal Haemoglobinuria. (PubMed, Pharmacoeconomics) - "This review systematically compares the clinical and cost-effectiveness evidence considered within the NICE single technology appraisals of iptacopan, danicopan and pegcetacoplan, examines the consistency of the clinical evidence and economic modelling, and considers whether single technology appraisals are a suitable apparatus for consistent decision making. This review raises the question of whether NICE should implement multiple technology appraisals more frequently to reduce these inconsistences. Additionally, we recommend the development of a framework for revisiting positive recommendations when the implementation of health technologies deviates from assumptions made in the economic modelling to ensure cost-effective healthcare is preserved."

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

Long-term Safety and Tolerability of Iptacopan in Patients With Paroxysmal Nocturnal Hemoglobinuria (clinicaltrials.gov) - P3 | N=208 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

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

Thrombosis at Unusual Sites: Focus on Myeloproliferative Neoplasms and Paroxysmal Nocturnal Hemoglobinuria. (PubMed, Hamostaseologie) - "Specific treatments for MPN may include phlebotomy or cytoreductive drugs such as hydroxyurea, anagrelide, pegylated interferon-alpha, or Janus kinase inhibitors. Drugs used for PNH treatment include terminal complement inhibitors, such as eculizumab and ravulizumab, as well as proximally acting inhibitors such as pegcetacoplan or iptacopan. Patients with MPN and PNH are at high risk for thrombosis during their entire lifetime and should thus be followed by specialists experienced in the care of these diseases."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

APPARENT: Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN (clinicaltrials.gov) - P3 | N=106 | Recruiting | Sponsor: Novartis Pharmaceuticals | N=68 ➔ 106 | Trial completion date: Nov 2026 ➔ May 2029 | Trial primary completion date: Oct 2026 ➔ Oct 2028

Enrollment change • Trial completion date • Trial primary completion date • Glomerulonephritis • Lupus Nephritis • Nephrology

APPELHUS: Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy (clinicaltrials.gov) - P3 | N=50 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2026 ➔ Mar 2029 | Trial primary completion date: Dec 2025 ➔ Sep 2028

Trial completion date • Trial primary completion date • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology

Treatment of Patients with IgA Nephropathy: A call for a new paradigm. (PubMed, Kidney Int) - "A multitude of new therapies are now being evaluated in IgAN, and several drugs, such as sodium-glucose transporter-2 inhibitors, sparsentan (a dual endothelin-1 and angiotensin II receptor blocker), nefecon (a targeted release formulation of budesonide) and iptacopan (a complement factor B inhibitor) have been approved, with more to come in the next few years. In this review, we propose a new treatment paradigm that combines therapies with different mechanisms of action to target the immune components and the chronic kidney disease components of IgAN in parallel to preserve long-term kidney survival."

Journal • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • CFB • EDN1

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 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease