Voydeya (danicopan) / AstraZeneca - LARVOL DELTA

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

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

FLOW CYTOMETRY IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: RELEVANCE OF THE MONITORIZATION OF THE ERYTHROID CLONE SIZE IN PATIENTS WITH COMPLEMENT INHIBITORS THERAPY. (EHA 2026) - "Methods We retrospectively analyzed 10 patients (9 adults, 1 pediatric) treated with different Ci (eculizumab, ravulizumab, pegcetacoplan, and danicopan) over a 26-years period. 1.Illingworth, A. J., Marinov, I., & Sutherland, D. R. (2019). International Journal of Laboratory Hematology , 41 , 73-81."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

EARLY ACCESS PROGRAM FOR DANICOPAN (ALXN2040) AS ADD-ON TREATMENT TO ECULIZUMAB OR RAVULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH): THE ITALIAN REAL-WORLD. (EHA 2026) - "To date, the median duration of danicopan+C5i was 13.2 months (range 3-21). Summary/Conclusion Danicopan added to C5i appeared to be a promising combination therapy for patients with PNH and clinically relevant residual EVH."

Clinical • Real-world • Real-world evidence • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Movement Disorders • Musculoskeletal Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

THROMBOEMBOLISM IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA IN THE ERA OF COMPLEMENT INHIBITORS – MULTICENTER ANALYSIS BY THE POLISH ADULT LEUKEMIA GROUP (EHA 2026) - "All patients received at least one dose of CI, with the first anti-complement treatment being eculizumab in 85 (62%) or ravulizumab in 42 (30.7%) patients. In total, 72 patients underwent at least one treatment modification, consisting of either a switch to another inhibitor (including proximal inhibitors) or the addition of danicopan...Summary/Conclusion The incidence of TE in PNH patients is substantial, with nearly 20% of them experiencing a thrombotic event (frequently intraabdominal), which may finally lead to the diagnosis of PNH. CIs significantly reduce the frequency of TEs, however, even in the era of complement inhibition, TE attributable to PNH remains a serious complication and may still result in patients' death."

Clinical • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

DANICOPAN ADD-ON THERAPY IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: UK EXPERIENCE (EHA 2026) - "It is approved for use in the UK as add-on therapy with either C5i ravulizumab or eculizumab, in patients who have clinically significant EVH. Despite dual complement inhibition, BTH rates are higher than those reported in danicopan clinical trial, and infection remains an important consideration as with all complement inhibitors. Danicopan is well tolerated and remains a good treatment option for patients with PNH and clinically significant EVH on C5i."

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

REAL-WORLD PATIENT-REPORTED TREATMENT BURDEN FROM 106 PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: RESULTS FROM THE VOICE CROSS-SECTIONAL QUANTITATIVE SURVEY (EHA 2026) - "Current treatment for most pts was complement inhibitor therapy (86%), most commonly ravulizumab (59%), crovalimab (11%), or iptacopan (10%); 12 pts received danicopan in combination with ravulizumab (n=11) or crovalimab (n=1). Figure. PNH treatment-related burden (N=106)"

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

Efficacy and Safety of Treatments for Paroxysmal Nocturnal Hemoglobinuria: A Systematic Literature Review. (PubMed, J Clin Med) - "The first treatments approved were complement 5 inhibitors (C5is), eculizumab and ravulizumab. Recently approved treatments include pegcetacoplan, iptacopan, danicopan (as an add-on to a C5i), and crovalimab... This SLR is the first to provide an overview of clinical trials assessing the efficacy and safety of all currently approved PNH treatments, which could help inform clinical decisions. Although some head-to-head trials are available, direct comparative evidence remains limited for several comparators, necessitating an indirect treatment comparison (ITC) to assess the efficacy and safety across the treatment landscape."

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

The complement system orchestrates the interaction between fibroblast-like synoviocytes and neutrophils in rheumatoid arthritis (EULAR 2026) - "Similar effects were observed using factor B inhibitor Iptacopan and factor D inhibitor Danicopan. These C3-driven adhesive changes promote neutrophil activation and NET formation, identifying FLS-derived C3 and integrin-mediated adhesion as key amplifiers of local neutrophil activation in RA. Image(s), graphic(s), or table(s)"

Immunology • Inflammation • Inflammatory Arthritis • Osteoarthritis • Rheumatoid Arthritis • Rheumatology • ICAM1 • ITGAM • NECTIN1 • VCAM1

Comment on "Consensus of the hematology society of Taiwan on the management of paroxysmal nocturnal hemoglobinuria (PNH)". (PubMed, J Formos Med Assoc) - No abstract available

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

Direct Switch From Iptacopan to Pegcetacoplan in a Patient With Paroxysmal Nocturnal Hemoglobinuria. (PubMed, EJHaem) - "Currently, patients with suboptimal response to C5 inhibitors may be switched to proximal complement inhibitors, such as pegcetacoplan, danicopan, or iptacopan...We report the first case of a direct switch from iptacopan to pegcetacoplan without re-exposure to C5 inhibitors. Direct switching between proximal complement inhibitors may represent a feasible and safe strategy, although further validation in larger cohorts is required."

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

Danicopan PMS in Korea (clinicaltrials.gov) - P=N/A | N=8 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

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

New Anticomplement Drugs in Nephrology - Mechanism and Indication. (PubMed, Kidney Blood Press Res) - "Anticomplement therapies represent a transformative advance in nephrology, offering targeted interventions that can improve outcomes for patients with complement-mediated kidney diseases. Their strategic use may reduce disease progression, manage inflammation, and mitigate organ damage, highlighting the potential of personalized treatment approaches in complement-driven renal disorders."

Journal • Review • ANCA Vasculitis • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Diabetic Nephropathy • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Nephrology • Renal Disease • Systemic Lupus Erythematosus • Vasculitis

DANICOPAN ADD-ON THERAPY DEMONSTRATES POSITIVE EFFICACY AND SAFETY IN ADVANCED AGE ADULTS WITH PNH AND CLINICALLY SIGNIFICANT EXTRAVASCULAR HEMOLYSIS: PHASE 3 ALPHA TRIAL SUB-ANALYSIS (EBMT 2026) - P3 | "This sub-analysis demonstrates that danicopan add-on to ravulizumab or eculizumab has positive efficacy and safety profile in advanced age patients with PNH and csEVH. During 12 weeks of danicopan therapy, patients reported meaningful improvements in Hb and ARC, maintained transfusion avoidance, and reported low rate of AEs."

Clinical • Metastases • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

DANICOPAN ADD-ON THERAPY DEMONSTRATES POSITIVE EFFICACY AND SAFETY IN ADVANCED AGE ADULTS WITH PNH AND CLINICALLY SIGNIFICANT EXTRAVASCULAR HEMOLYSIS: PHASE 3 ALPHA TRIAL SUB-ANALYSIS (EBMT 2026) - P3 | "This sub-analysis demonstrates that danicopan add-on to ravulizumab or eculizumab has positive efficacy and safety profile in advanced age patients with PNH and csEVH. During 12 weeks of danicopan therapy, patients reported meaningful improvements in Hb and ARC, maintained transfusion avoidance, and reported low rate of AEs."

Clinical • Metastases • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Low Risk for Meningococcal Infections with Systemically Administered Pegcetacoplan, a Complement C3 and C3b Inhibitor (THSNA 2026) - P3 | "Clinical benefits of the initially available C5 inhibitors that block terminal complement activation (eculizumab, ravulizumab, crovalimab) paved the way for the development of proximal inhibitors, including the C3/C3b inhibitor pegcetacoplan, the factor B inhibitor iptacopan, and the add-on (to C5 inhibitors) factor D inhibitor danicopan. Understanding the safety profile of pegcetacoplan and other complement-targeted therapies will help physicians and patients make informed treatment decisions for individuals with complement-mediated conditions. For over 7 years of total systemic pegcetacoplan exposure, no cases of encapsulated N. meningitidis and consistently low rates of infections by other encapsulated bacteria were observed in patients with PNH, C3G, primary IC-MPGN, or other conditions. These findings may reflect effective risk mitigation strategies."

Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Immunology • Infectious Disease • Influenza • Lupus Nephritis • Meningococcal Infections • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Pneumococcal Infections • Pneumonia • Primary Immunodeficiency • Rare Diseases • Respiratory Diseases • Septic Shock

Danicopan PMS in Korea (clinicaltrials.gov) - P=N/A | N=8 | Not yet recruiting | Sponsor: AstraZeneca

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

Population PK-PD Modeling of Danicopan Add-On Therapy in Participants With Paroxysmal Nocturnal Hemoglobinuria Treated With Ravulizumab or Eculizumab. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Overall, the effects of demographics, baseline, and food status variables were not considered clinically significant. These findings support the approved 150 mg and 200 mg tid dosing regimens for danicopan in patients with PNH."

Journal • PK/PD data • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease

Assess Long-Term Safety of Danicopan Add-on Therapy in Participants With Paroxysmal Nocturnal Hemoglobinuria: Analysis of IPIG-Registry Data (clinicaltrials.gov) - P=N/A | N=50 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc.

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

Long-term Safety of Danicopan: IPIG Registry-based Cohort Study (clinicaltrials.gov) - P=N/A | N=50 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc.

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

Understanding Pharmacokinetic-Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2024 to Better Manage the Risk of Drug Interactions With Concomitant Medications: A Review of Clinical Data From New Drug Applications. (PubMed, Curr Ther Res Clin Exp) - "Of these, 7 drugs were substrates of CYP3A, 3 of CYP2C9, one of CYP1A2, and one of CYP2C8, including the sensitive substrates vanzacaftor (CYP3A) and vorasidenib (CYP1A2). As precipitants, 6 drugs (acoramidis, cefepime/enmetazobactam, givinostat, lazertinib, mavorixafor, and resmetirom) were clinical inhibitors of CYP enzymes (2C8, 2C9, 2D6, 2E1, and 3A), with mavorixafor being a CYP2D6 strong inhibitor. Two drugs (elafibranor and tovorafenib) showed weak induction of CYP3A. Regarding transporter data, 3 drugs were substrates of transporters, including seladelpar (BCRP and OAT3), sulopenem (OAT3), and vadadustat (OAT1/3), and 8 drugs (arimoclomol, danicopan, givinostat, lazertinib, mavorixafor, resmetirom, vadadustat, and vazacaftor/tezacaftor/deutivacaftor) were inhibitors of transporters...Several DDIs with an AUC change <2 also had labeling recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index. Mechanistic DDI..."

Clinical data • FDA event • Journal • NDA • PK/PD data • Review • CYP1A2 • CYP2C9

Advancing treatment goals for paroxysmal nocturnal hemoglobinuria to align with quality of life improvements in the era of anti-complement therapy (PubMed, Rinsho Ketsueki) - "Eculizumab, a C5 inhibitor introduced in 2010, directly inhibits intravascular hemolysis, and thus not only resolves hemolysis-related symptoms but also prevents organ damage and improves survival...Various drugs have been developed to address these issues, including long-acting C5 inhibitors (ravulizumab and crovalimab) and proximal complement inhibitors capable of blocking extravascular hemolysis, such as a C3 inhibitor (pegcetacoplan), a factor B inhibitor (iptacopan), and a factor D inhibitor (danicopan). In particular, proximal complement inhibitors further enhance QOL because they inhibit both intravascular and extravascular hemolysis, resulting in greater improvement of hemoglobin levels and transfusion independence, and thereby further enhancing of QOL. Today, it is possible to achieve optimal improvement in QOL by appropriately selecting one of the three C5 inhibitors as first-line therapy or one of the three proximal complement inhibitors as second-line..."

HEOR • Journal • Cardiovascular • Chronic Kidney Disease • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Thrombosis

Systemic medications and their impact on age-related macular degeneration development and progression: a review of current evidence. (PubMed, Curr Opin Ophthalmol) - "Multiple systemic medications have highlighted mixed or stage-dependent benefits on AMD development and progression. Some agents such as metformin and aspirin have shown conflicting findings, having been evaluated in randomized trials and large observational studies. Other medications including GLP-1 agonists, dopamine agonists, statins, fenofibrates, and danicopan show early promise in more limited studies, but require further clinical validation."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Ravulizumab-danicopan combination therapy in PNH management. (PubMed, Clin Adv Hematol Oncol) - No abstract available

Journal