Voydeya (danicopan) / AstraZeneca - LARVOL DELTA

Study of Danicopan as Add-on Treatment to Ravulizumab or Eculizumab in Pediatric Participants With PNH Who Have Clinically Significant Extravascular Hemolysis (clinicaltrials.gov) - P3 | N=6 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Feb 2028 ➔ Jul 2028 | Trial primary completion date: Feb 2027 ➔ Jul 2027

Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Pediatrics • Rare Diseases

Game Changers: Blockbuster Small-Molecule Drugs Approved by the FDA in 2024. (PubMed, Pharmaceuticals (Basel)) - "Notably, eight of these drugs (including Rezdiffra®, Voydeya®, Iqirvo®, Voranigo®, Livdelzi®, Miplyffa®, Revuforj®, and Crenessity®) are classified as "first-in-class" and have received breakthrough therapy designation. These agents not only exhibit distinct mechanisms of action but also offer substantial improvements in efficacy for patients compared to prior therapeutic options. This article offers a comprehensive analysis of the mechanisms of action, clinical trials, drug design, and synthetic methodologies related to representative drugs, aiming to provide crucial insights for future pharmaceutical development."

FDA event • Journal • Review • Alopecia • Brain Cancer • Breast Cancer • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Congenital Adrenal Hyperplasia • Cystic Fibrosis • Dermatology • Duchenne Muscular Dystrophy • Endocrine Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Glioma • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Immunology • Infectious Disease • Leukemia • Lung Cancer • Lysosomal Storage Diseases • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Muscular Dystrophy • Nephrology • Non Small Cell Lung Cancer • Oncology • Primary Biliary Cholangitis • Psychiatry • Pulmonary Disease • Renal Disease • Respiratory Diseases • Schizophrenia • Solid Tumor • Ventricular Tachycardia

Complement Factor D Plays a Crucial Role in Metabolic and Pro-inflammatory Reprogramming of Vascular Fibroblasts in Pulmonary Hypertension (ATS 2025) - "Further in this study, we repurposed commercially available CFD inhibitors, particularly Danicopan and Vimircopan...This study highlights the crucial role of local and intracellular complement proteins, particularly CFD, in PH fibroblasts. Targeting CFD significantly reduced production of C3-activated fragments (C3a) and metabolites and genes associated with metabolic and pro-inflammatory reprogramming."

Cardiovascular • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ACO1 • CFD • CXCL12 • ENO1 • IL13 • IL33 • IL6 • SLC2A1

SUSTAINED LONG-TERM CONTROL OF TERMINAL COMPLEMENT ACTIVITY WITH RAVULIZUMAB OR DANICOPAN ADD-ON TO RAVULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (EHA 2025) - P3 | "The complement C5 inhibitor (C5i) ravulizumab has shown effective control of terminal complement activity and intravascular hemolysis (IVH), reduced thrombosis and improved survival for up to 6 years, based on data from two phase 3 trials.1,2 In patients with PNH with clinically significant extravascular hemolysis (csEVH), addition of danicopan, a factor D inhibitor, to ravulizumab or eculizumab demonstrated a favorable benefit-risk profile through 72 weeks, providing sustained control of terminal complement activity, IVH, and csEVH in the phase 3 ALPHA study.3,4 Aims: To characterize long-term outcomes, including breakthrough IVH (BT-IVH) events, of ravulizumab and danicopan add-on to ravulizumab or eculizumab in patients with PNH, using pivotal phase 3 trial data. In patients with PNH, ravulizumab effectively controls terminal complement activity over a long-term period. Danicopan add-on to ravulizumab is effective in managing csEVH while controlling terminal..."

Clinical • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections • Novel Coronavirus Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

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

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

DANICOPAN ADD-ON THERAPY TO RAVULIZUMAB OR ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA AND CLINICALLY SIGNIFICANT EXTRAVASCULAR HEMOLYSIS STRATIFIED BY BONE MARROW FAILURE HISTORY (EHA 2025) - P3 | "Regardless of BMF history, danicopan add-on therapy to ravulizumab or eculizumab, showed improvements in hematologic parameters (ARC and Hb levels) up to week 12. These findings demonstrate the benefit of danicopan in addition to C5 inhibitors in a broad range of patients with PNH.Brodsky RA. Blood 2014; 124:2804-11.Lee JW."

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

Horizon Scanning for Paroxysmal Nocturnal Hemoglobinuria in Brazil: Insights on Past Trends and Future Prospects (ISPOR 2025) - " 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

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) AND MYELODYSPLASIA: A RETROSPECTIVE ANALYSIS FROM A HEMATOLOGY CENTER. (EHA 2025) - "Further characteristics are listed in the table.NoSexDate of diagnosis (mm/yy)Age at diagnosisBM-cytology/histologyCytogeneticsMolecular geneticsPlatelets(/µl)Therapy in 02/251 (a)w02/9624nanaPIGA VAF 33%BCOR VAF 30%70,000 -100,000Ravulizumab2 (b)w07/0220nanana180,000 -230,000w+w3w12/0957Hemolysisnana180,000 -270,000Ravulizumab + Danicopan4 (c)w01/1217nanana170,000 -250,000Eculizumab5 (d)m12/1932Hemolysis,T-MDS46,XY [20]PIGABCOR90,000 - 120,000Ravulizumab 6m05/2081Hemolysis,MDS-RS-MLD46,XY [20]SF3B1 not mutatedU2AF1 VAF 40%TET2 (Var, Tier 3) VAF 37%PIGA na49,000 -90,000Iptacopan7w08/2184Hemolysis,dysplasia46,XX,del(13)(q14q31) [7], 46,XX [13],PIGA45,000 -79,000Ravulizumab8w11/2329Hemolysis,dysplasia46,XX [20]PIGA VAF 6%BCOR VAF 4%31,000 -63,000Ravulizumab9 (e)m02/2465Hypoplastic MDS46,XY [20]BCOR (Tier2)PIGA not mutated (<3%)21,000 -34,000w+wAbbreviations: na= not available, T-MDS= therapy-related MDS; MDS-RS-MLD= MDS with ringsideroblasts and multi-lineage..."

Retrospective data • Agranulocytosis • Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Genito-urinary Cancer • Granulocytopenia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Solid Tumor • Testicular Cancer • Thrombocytopenia • BCOR • SF3B1 • TET2

Breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria throughout clinical trials: from definition to clinical practice. (PubMed, Blood) - "In particular, BTH may occur with all complement inhibitors, with a frequency of 10-15% over 6 months with eculizumab, crovalimab, and pegcetacoplan, and <5% with ravulizumab, iptacopan, and danicopan plus anti-C5. Complement amplifying conditions were observed in about half of cases and were more frequently infections. Treatment adherence, optimization of the administration schedule, anticoagulant prophylaxis, as well as education of patients and physicians remain important factors to prevent BTH and its complications."

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

Advancing Landscape of Paroxysmal Nocturnal Hemoglobinuria Treatment. (PubMed, Turk J Haematol) - "With an improved understanding of PNH biology, a focused effort on complement inhibitors led to the discovery of eculizumab, a C5 inhibitor initially approved by the FDA in 2007. Further advancements in drug development for PNH include improved pharmacokinetics with ravulizumab in 2018 and the introduction of proximal complement inhibitors such as pegcetacoplan (2021), iptacopan (2023), and danicopan (2024), and crovalimab (2024) to enhance patient outcomes. With these new proximal and distal complement inhibitors in the treatment landscape, it is timely for clinicians to review the evolving landscape of PNH treatments and patient selection."

Journal • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

ALXN2040-PNH-303: A Long-term Safety and Efficacy Study of Danicopan as an Add-on Therapy to Complement Component 5 Inhibitor (C5i) in Participants With PNH (clinicaltrials.gov) - P3 | N=80 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Jan 2027 ➔ Aug 2026 | Trial primary completion date: Jan 2027 ➔ Aug 2026

Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

First cases of danicopan use in adolescent patients with paroxysmal nocturnal haemoglobinuria. (PubMed, Br J Haematol) - No abstract available

Journal • Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria

DANICOPAN AS ADD-ON THERAPY TO RAVULIZUMAB OR ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: LONG-TERM PATIENT-REPORTED OUTCOMES FROM THE PHASE 3 ALPHA TRIAL (EBMT 2025) - P3 | "In patients with PNH and csEVH, long-term danicopan add-on therapy to ravulizumab or eculizumab resulted in sustained improvements in patient-reported fatigue, QoL and physical function up to wk72, with scores reaching those in the general population. These findings indicate that danicopan add-on therapy is a potential solution for improving QoL in patients with PNH and severe csEVH."

Clinical • P3 data • Patient reported outcomes • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

DANICOPAN AS ADD-ON THERAPY TO RAVULIZUMAB OR ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: LONG-TERM PATIENT-REPORTED OUTCOMES FROM THE PHASE 3 ALPHA TRIAL (EBMT 2025) - P3 | "In patients with PNH and csEVH, long-term danicopan add-on therapy to ravulizumab or eculizumab resulted in sustained improvements in patient-reported fatigue, QoL and physical function up to wk72, with scores reaching those in the general population. These findings indicate that danicopan add-on therapy is a potential solution for improving QoL in patients with PNH and severe csEVH."

Clinical • P3 data • Patient reported outcomes • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

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

Study of Danicopan as Add-on Treatment to Ravulizumab or Eculizumab in Pediatric Participants With PNH Who Have Clinically Significant Extravascular Hemolysis (clinicaltrials.gov) - P3 | N=6 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

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

Advice - whether or not to reimburse danicopan (Voydeya) for the treatment of paroxysmal nocturnal hemoglobinuria [Google translation] (Netherlands Healthcare Institute) - "The Dutch Healthcare Institute will assess whether danicopan (Voydeya) can be reimbursed. This medicine can be used in the treatment of certain patients with paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare bone marrow disease. If we give a positive recommendation and the Minister of Health, Welfare and Sport (VWS) accepts our recommendation, danicopan will be included in the Medicines Reimbursement System (GVS). Only then will this medicine be reimbursed from the basic health insurance package."

Reimbursement • 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

A Study of Danicopan in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P2 | N=365 | Completed | Sponsor: Alexion Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Aug 2025 ➔ Jan 2025

Trial completion • Trial completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Full Year and Q4 2024 results (AstraZeneca Press Release) - "Ultomiris Total Revenue includes sales of Voydeya, which is approved as an add-on treatment to Ultomiris and Soliris for the 10-20% of PNH patients who experience clinically significant EVH....Combined sales of Tezspire, recorded by Amgen and AstraZeneca, amounted to $1,219m in FY 2024 (FY 2023: $653m)."

Commercial • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria. (PubMed, Front Immunol) - "Non-transplant PNH therapies include anti-C5 monoclonal antibodies that reduce terminal complement activation (eculizumab, ravulizumab, and crovalimab) and proximal complement pathway inhibitors such as pegcetacoplan (C3 inhibitor), iptacopan (complement factor B inhibitor), and danicopan (complement factor D inhibitor)...In the case of severe aplastic anemia with an associated PNH clone, immunoablative protocols based on anti-thymocyte globulin serotherapy with fludarabine and cyclophosphamide are recommended. The use of reduced toxicity protocols with fludarabine has been well-documented in patients with classic PNH. A treosulfan/fludarabine-based regimen is recommended; however, there is no consensus on optimal drug selection."

Journal • Review • Aplastic Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Graft versus Host Disease • Hematological Disorders • Immunology • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • Transplantation • CFB

Real-World Adherence with Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria Compared with Previously Reported Oral Medication Adherence Rates (ASH 2024) - "Several complement inhibitors are approved for PNH, including the intravenous or subcutaneous C5 inhibitors (C5is) eculizumab, ravulizumab, and crovalimab; the subcutaneous self-administered C3 inhibitor pegcetacoplan; and the oral factor B inhibitor iptacopan and factor D inhibitor danicopan (as add-on therapy to a C5i)...OAC adherence rates in AF range widely (~40% to ~90%), differing across countries, patient populations (incident AF vs. post cardiovascular event), OAC types (warfarin, direct OACs), and follow-up period lengths...2020; 26 : 186].Pegcetacoplan adherence for PNH in the US postmarketing setting from launch (2021) to date (2024) was estimated at 97%, well above the 80% threshold defining medication adherence in the literature.Conclusions : Real-world patients with PNH who self-administer pegcetacoplan subcutaneously have adherence rates exceeding the reported real-world adherence rates for oral medications in chronic conditions, especially those with high..."

Adherence • Clinical • HEOR • Real-world • Real-world evidence • Atrial Fibrillation • Cardiovascular • Complement-mediated Rare Disorders • Diabetes • Hematological Disorders • Hematological Malignancies • Metabolic Disorders • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • Type 2 Diabetes Mellitus

Current Real-World Treatment Landscape for Patients with Paroxysmal Nocturnal Hemoglobinuria in the United States (ASH 2024) - "CI therapies included eculizumab, ravulizumab, pegcetacoplan, iptacopan, danicopan, and crovalimab. Following its approval, uptake of iptacopan among patients with PNH has been rapid in US real-world clinical practice, with 14% of CI-treated patients currently receiving iptacopan as their most recent therapy. Nonetheless, the majority of included patients with PNH did not have a claim for a CI therapy during the study period, despite the availability of six approved CI therapies."

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

Optimizing Complement Inhibitor Monitoring in PNH and Beyond (ASH 2024) - "Results : In vitro addition of C5 inhibitors (eculizumab, ravulizumab, crovalimab) to healthy control serum demonstrated a dose-dependent increase of complement blockade in GVB++ buffer. In isolated AP buffer, we observed dose-dependent inhibition with increasing concentrations of eculizumab, danicopan (factor D inhibitor), iptacopan (factor B inhibitor), and pegcetacoplan (C3 inhibitor)...Interestingly, in the baseline and 1-week serum, either danicopan or sutimlimab completely inhibited AP activity...Using this assay, EVH can be more precisely defined as full blockade of complement activity with persistent evidence of hemolysis. Furthermore, the assay has applications for not only PNH but also other diseases in which complement inhibitors are indicated, such as atypical hemolytic uremic syndrome."

Anemia • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • CD46 • CD55 • CD59