Fabhalta (iptacopan) / Novartis - LARVOL DELTA

Complement factor B blockade by iptacopan drives antitumor complement-based immunomodulation in pancreatic cancer microenvironment. (PubMed, Am J Pathol) - "Combination therapy with immune checkpoint blockades (anti-PD-1 and anti-CTLA-4) further augmented antitumor effects, and triple therapy with gemcitabine/nab-paclitaxel yielded the greatest tumor suppression. These results demonstrate that iptacopan exerts dual antitumor effects by inducing tumor-intrinsic senescence and promoting an immunostimulatory tumor immune microenvironment. Therefore, CFB inhibition represents a promising complement-based immunomodulatory treatment for PDAC."

IO biomarker • Journal • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • CDKN1A • CFB • FOXP3

Complement targeting in autoimmune diseases. (PubMed, Curr Opin Hematol) - "Recognizing complement's role in the pathophysiology of hematological and autoimmune diseases has driven effective new therapies. Comprehensive profiling complement biomarkers, now feasible through complementomics in fluids and tissues, may reveal responsive endotypes and optimal cascade steps to target in diseases where complement is implicated but trials have not yet matched the right drug to the right patients."

Journal • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Systemic Lupus Erythematosus

Management strategies for post-transplant IgA nephropathy in kidney transplant recipients: a scoping review. (PubMed, BMC Nephrol) - "RAAS-blockade was the most commonly used intervention and was associated with benefit in several studies. Tonsillectomy was associated with improved outcomes but reported only in Japanese cohorts. Other interventions (rituximab, pulsed steroids, emerging therapies) warrant prospective clinical trials. Amid evolving paradigms in native IgAN management, this review highlights heterogeneity in diagnostic criteria, outcome reporting, and interventions for the management of post-transplant IgAN. Robust prospective, multicentre studies are urgently required to define optimal management in this high-risk population."

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease • Transplantation

Safety and Efficacy of Iptacopan in Patients With High-Risk Transplantation-Associated Thrombotic Microangiopathy (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: First Affiliated Hospital of Zhejiang University | Not yet recruiting ➔ Recruiting | Initiation date: Jan 2026 ➔ Aug 2026

Enrollment open • Trial initiation date • Bone Marrow Transplantation • Hematological Disorders • Transplantation • Transplantation Associated Thrombotic Microangiopathy

Complement-targeted therapies for C3 glomerulopathy and atypical hemolytic uremic syndrome: a time-limited rapid systematic review with narrative synthesis. (PubMed, Front Med (Lausanne)) - "The abbreviated timeframe was chosen to inform clinical practice following the March 2025 FDA approval of iptacopan and the July 2025 FDA approval of pegcetacoplan for C3G, at a time when clinicians required timely guidance on emerging therapeutic options...In C3G, eculizumab showed heterogeneous responses...This review employed narrative synthesis without meta-analysis; readers should not interpret reported percentages as pooled estimates. CRD420261364711 (rapid registration, 9 April 2026)."

Journal • Review • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Infectious Disease • Meningococcal Infections • Nephrology • Renal Disease

Novartis iptacopan was granted FDA orphan designation as a treatment of atypical hemolytic uremic syndrome, according to a post to the agency’s website (TipRanks)

Orphan drug • Atypical Hemolytic Uremic Syndrome

Global research landscape of C3 glomerulopathy: A bibliometric analysis. (PubMed, Clin Nephrol) - "Global research on C3G has evolved from descriptive pathology toward precision complement therapeutics. However, significant geographical disparities persist, emphasizing the need for stronger international collaboration and equitable access to emerging complement inhibitors."

Journal • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Pediatrics • Renal Disease

A Phase III Study to Investigate Efficacy, Safety and Tolerability of Iptacopan Compared With Placebo in Participants Aged 18 to 85 Years With gMG. (clinicaltrials.gov) - P3 | N=146 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Myasthenia Gravis

Methodological pitfalls in indirect treatment comparisons: insights from a recent systematic review and analysis for C3 glomerulopathy. (PubMed, J Comp Eff Res) - "This appraisal evaluates the feasibility of applying ITC principles to compare Phase III trials of iptacopan (APPEAR-C3G) and pegcetacoplan (VALIANT) in the absence of head-to-head evidence. Consequently, payers, decision makers, and HTA bodies should interpret existing C3G ITCs with caution. These findings inform broader application of ITC methods in rare diseases, identifying areas for future evidence generation and analytical innovation."

Journal • Review • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology • Rare Diseases • Renal Disease

Sibeprenlimab (Voyxact) for primary immunoglobulin A nephropathy. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

Case report: Sequential complement inhibition and BAFF/APRIL blockade in progressive IgA nephropathy and IgA vasculitis nephritis: a report of two cases. (PubMed, Front Immunol) - "Both patients showed substantial reductions in proteinuria and stabilization of kidney function during follow-up. These cases suggest that multi-pathway targeted therapy may represent a promising approach for selected patients with aggressive IgAN or IgAVN."

Journal • Glomerulonephritis • IgA Nephropathy • Inflammation • Nephrology • Renal Disease • Vasculitis

Approved therapies in the IgA nephropathy armamentarium: a summary of the evidence. (PubMed, Kidney Int Suppl (2011)) - "Recent approvals include Nefecon, sparsentan, iptacopan, atrasentan, and sibeprenlimab. Nefecon, a targeted-release formulation of budesonide, is the only US Food and Drug Administration and European Medicines Agency fully approved agent that is designed to target the primary source of IgAN: galactose-deficient IgA1 production in the gut mucosa...Sparsentan demonstrated a significant reduction in proteinuria and estimated glomerular filtration rate decline compared with irbesartan...The endothelin A receptor antagonist atrasentan and A proliferation binding ligand inhibitor sibeprenlimab have also received accelerated US Food and Drug Administration approval, based on interim phase 3 results showing significant proteinuria reduction versus placebo in patients with IgAN. This expanded clinical armamentarium offers clinicians and patients greater choice and improved disease control in IgAN management."

Journal • Review • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Renal Disease • CFB

Management of IgA nephropathy and the expanding role of immunomodulation. (PubMed, Kidney Int Suppl (2011)) - "Targeted therapies, such as Nefecon (targeted-release formulation budesonide) and iptacopan, which address the immune-mediated pathogenic triggers of nephron loss, are important additions. Lifestyle modification, renin-angiotensin system inhibition, sodium-glucose cotransporter-2 inhibitors, and newer agents, such as sparsentan and atrasentan, are also available to manage the generic responses to IgAN-induced nephron loss common to many forms of proteinuric chronic kidney disease. As our understanding of the pathogenic mechanisms underlying disease progression in IgAN has expanded, so has the recognition that IgAN-specific, targeted immunomodulatory therapies are needed, and that these can be used in combination with other agents addressing the more generic causes of nephron loss. These approaches together can help to modify the course of the disease in patients and avoid progression to kidney failure."

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

IgA nephropathy management: what does the future hold? (PubMed, Kidney Int Suppl (2011)) - "Two agents have been fully approved for use in patients with IgAN in some regions: Nefecon, an oral targeted-release formulation of budesonide, and sparsentan, a dual endothelin A and angiotensin II receptor antagonist. Iptacopan and atrasentan are conditionally approved on the basis of proteinuria data; full approval will be evaluated once data on kidney function are available...Combination therapies with different classes of drugs will likely become the new standard of care for chronic kidney disease as they target distinct pathogenic mechanisms or "hits" (namely, hemodynamic, immune, galactose-deficient IgA1-generating, inflammatory, and fibrotic processes involved in IgAN and chronic kidney disease progression). To improve personalized care for patients with IgAN, further research is needed to identify and validate noninvasive biomarkers for diagnosis, prognosis, treatment selection, and monitoring response."

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

Pivotal Clinical Trials in C3 Glomerulopathy: answers and remaining uncertainties. (PubMed, Nephrol Dial Transplant) - "The publication of pivotal phase 3 trials evaluating proximal complement inhibitors -iptacopan, a selective factor B inhibitor, and pegcetacoplan, a C3 inhibitor- marks a turning point in the management of C3G and IC-MPGN. We emphasize the need for long-term outcome studies, precision-based therapeutic strategies, and pragmatic real-world data. Ultimately, the challenge ahead is not whether complement inhibition is effective but how best to deploy these therapies to maximize durable benefit, minimize risk, and ensure equitable access."

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

Beyond Terminal Blockade: A Mechanism-Based Approach to Complement Inhibitor Selection in Paroxysmal Nocturnal Hemoglobinuria. (PubMed, Drug Des Devel Ther) - "The proximal complement inhibitors pegcetacoplan (C3), iptacopan (Factor B), and danicopan (Factor D) address EVH-driven anemia but have not been evaluated in trials powered for thrombosis prevention, creating an asymmetry in the evidence base that demands explicit clinical reasoning. This review proposes a phenotype-driven longitudinal management strategy stratifying treatment decisions by dominant disease mechanism, thrombotic risk, and practical treatment context. Diagnostic approaches to differentiating EVH‑dominant, BMF‑dominant, and overlap phenotypes in the relevant patient subsets, comparative evidence across inhibitor classes, and mechanism-based escalation strategies are addressed in sequence, alongside high-risk clinical scenarios and an evidence-gap analysis to guide future research."

Journal • Review • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Venous Thromboembolism

Proximal Versus Terminal Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria with Residual Anemia: A Systematic Review and Pairwise Meta-Analysis of Randomized Controlled Trials (ISTH 2026) - "Proximal complement inhibitors targeting C3 (pegcetacoplan), factor B (iptacopan), or factor D (danicopan) address both intravascular and extravascular hemolysis. Table or Figure Upload (1) Table 1. Pooled efficacy outcomes: proximal inhibitor monotherapy versus C5 inhibitors Page 2 DOI*10.1016/j.rpth.2026.104819"

Retrospective data • Review • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Novartis Fabhalta (iptacopan) receives FDA traditional approval as first and only complement inhibitor to significantly slow kidney function decline in primary IgAN (GlobeNewswire) - "Fabhalta, a first-in-class complement inhibitor, received approval under a priority review designation after an initial FDA accelerated approval in August 2024 for the reduction of proteinuria in primary IgAN....The approval of Fabhalta was based on data from the Phase III APPLAUSE-IgAN study....Fabhalta slowed eGFR decline by 48% vs placebo over two years, demonstrating kidney function preservation."

FDA approval • IgA Nephropathy

Switching between complement inhibitors in paroxysmal nocturnal hemoglobinuria: Analysis of strategy, efficacy, and safety. (PubMed, Hemasphere) - "Clinical trials for the approved PI pegcetacoplan, iptacopan, and C5i + danicopan had clear protocols for changing from terminal to PI, extrapolated into real-world practice. Patients should be monitored closely for hemolysis, especially when changing from proximal-to-terminal inhibition. Prospective clinical/laboratory analysis is recommended for further clarification management for this patient group."

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

Complement System Inhibitors in Nephrology: A Comprehensive Review. (PubMed, G Ital Nefrol) - "Terminal complement inhibitors (eculizumab and ravulizumab) have revolutionized the treatment of atypical haemolytic uremic syndrome, demonstrating remarkable improvements in renal outcomes and survival. Proximal pathway inhibitors targeting Factor B (Iptacopan) and C3 (pegcetacoplan) show promise in C3 glomerulopathy and IgA nephropathy, with recent phase 3 trials demonstrating significant proteinuria reduction. Additional applications include immune complex membranoproliferative glomerulonephritis and ANCA-associated vasculitis, in which complement activation contributes to disease pathogenesis. However, these agents present unique challenges, including infection risk, particularly meningococcal disease, cost considerations, and uncertainty regarding optimal treatment duration."

Journal • Review • ANCA Vasculitis • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Lupus Nephritis • Meningococcal Infections • Nephrology • Renal Disease • Vasculitis

Efficacy and Safety of Iptacopan in Patients With Generalized Myasthenia Gravis: APPRAISE Study Design (ICNMD 2026) - 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

ROUTE-C3G: A Study of Complement 3 Glomerulopathy (C3G) Patients Treated With Iptacopan Through an Early Access Program in Spain (clinicaltrials.gov) - P=N/A | N=35 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals | Initiation date: May 2026 ➔ Aug 2026

Trial initiation date • Glomerulonephritis

REAL-WORLD OUTCOMES OF IPTACOPAN IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) PATIENTS: INSIGHTS FROM THE FRENCH EARLY ACCESS PROGRAM. (EHA 2026) - "Background Iptacopan is the 1 st oral monotherapy targeting Factor B to inhibit the proximal alternative complement pathway, effectively controlling both intra and extravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). Patients with Hb 10 g/dL remained stable without BTH reported. Overall, no new safety signals were identified."

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

A Study of Iptacopan in Korean Patients With Paroxysmal Nocturnal Hemoglobinuria or C3 Glomerulopathy (clinicaltrials.gov) - P=N/A | N=21 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

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

Fabhalta Capsules Specified Drug-use Survey (clinicaltrials.gov) - P=N/A | N=32 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=50 ➔ 32

Enrollment change • Enrollment closed • Complement-mediated Rare Disorders • Glomerulonephritis