Alhemo (concizumab-mtci) / Novo Nordisk - LARVOL DELTA

Novo Nordisk A/S withdrew its application to extend the use of Alhemo to children below 12 years of age with haemophilia A or haemophilia B, with or without factor VIII or IX inhibitors. (European Medicines Agency) - "The company withdrew the application on 10 September 2026...The company presented partial data from an ongoing study which was to involve at least 127 children below 12 years of age with haemophilia A or B, with or without inhibitors. At the time of submission, data from a group of 42 children, all with inhibitors, were presented...Based on the review of the information, at the time of the withdrawal, the Agency had concerns and its provisional opinion was that, with the information provided at that stage, Alhemo could not have been authorised to prevent bleeding episodes in children below 12 years of age with haemophilia A or haemophilia B, with or without inhibitors....The company submitted efficacy results from a subgroup of 30 children, all with inhibitors, who had completed the study. Key safety and efficacy data were missing, including efficacy data for children without inhibitors and those younger than 2 years of age."

European regulatory • Hemophilia A • Hemophilia B

Transforming Hemophilia Treatment With Novel Rebalancing Agents: Clinical Studies and Practical Perspectives. (PubMed, Clin Appl Thromb Hemost) - "Rebalancing agents, including fitusiran (antithrombin-lowering small interfering ribonucleic acid), concizumab and marstacimab (tissue factor pathway inhibitor antagonists), are novel nonfactor therapies that restore hemostatic balance by targeting natural anticoagulants rather than replacing missing clotting factors. In addition, the use of rebalancing agents in pediatric patients (<12 years old) remains under investigation. While promising, successful implementation depends on individualized treatment approaches, appropriate monitoring protocols, and thorough patient education to improve current care for PwH."

Journal • Review • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Pediatrics • Rare Diseases

Bridging the Gap: A Systematic Review of Modern Hemophilia Therapies and Global Inequities in Clinical Trial Participation. (PubMed, Haemophilia) - "Modern therapies demonstrate strong efficacy and acceptable safety, with several approved agents. However, persistent global inequities in trial participation and access highlight the need for more inclusive research and equitable implementation strategies."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

The Tissue Factor-TFPI Pathway as a Therapeutic Target in Bleeding Disorders of Unknown Cause. (PubMed, J Thromb Haemost) - "These findings identify dysregulation of the TF-TFPI axis as a potential pathophysiological mechanism underlying bleeding in a subset of patients with BDUC and highlight TFPI inhibition and rFVIIa administration as potential therapeutic approaches. However, the absence of abnormalities in all patients supports the concept that BDUC represents a biologically heterogeneous group of disorders with multiple underlying mechanisms."

Journal • Hematological Disorders

New and novel pharmacotherapies for hemophilia A: an update. (PubMed, Expert Opin Pharmacother) - "In replacement therapy, efanesoctocog alfa maintains normal-to-near-normal factor VIII (FVIII) levels weekly by bypassing endogenous von Willebrand factor dependence. In non-replacement therapies, the focus centers on rebalancing agents - the anti-tissue factor pathway inhibitor (TFPI) monoclonal antibodies concizumab and marstacimab, and the antithrombin-targeting small interfering RNA (siRNA) fitusiran - as well as next-generation FVIII-mimetics like denecimig...Rebalancing therapies present potential thromboembolic risks, complex breakthrough bleed protocols, and standard laboratory assay interference (requiring antithrombin monitoring or specialized assays). Critical goals for contemporary hemophilia management include tailoring therapies through multidisciplinary collaboration, monitoring subclinical joint disease via point-of-care ultrasound, and implementing standardized, real-world protocols for emergency hemostasis."

Journal • Review • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Rheumatology

Concizumab prophylaxis in a 2-year-old patient with severe hemophilia B and inhibitor: a case report. (PubMed, Front Pharmacol) - "We highlight an individualized early drug-level-guided dose escalation approach in a very young child, demonstrating that pharmacokinetic monitoring can be utilized proactively to optimize therapeutic response in this age group, leading to effective drug levels and excellent clinical response. This case supports the role of concizumab in potentially reducing treatment burden and improving hemostatic outcomes in young patients with severe hemophilia B and inhibitors."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Pediatrics • Rare Diseases

Thrombin generation of hemophilia B-causing factor IX variants with non-factor therapies (ISTH 2026) - "Methods TG of FIX-variant purified recombinant protein or HB-patient plasma was determined with therapeutic (or likely therapeutic) concentrations of FVIIIa-mimetics (300 nM emicizumab, 34 nM Mim8, 10 nM Inno8) and anti-TFPI antibodies (30 nM concizumab,113 nM mastacimab-SIA). Bars represent mean of ≥2 experiments done in duplicate and error bars are SEM. Page 2 DOI*10.1016/j.rpth.2026.104810"

Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Advances in treatments for hemophilia A/B with inhibitors: current treatment gaps and promising therapies. (PubMed, Expert Rev Hematol) - "A literature search was conducted using PubMed/MEDLINE, Embase, and Google Scholar for publications from January 2000 to March 2026 using combinations of the terms 'hemophilia A,' 'hemophilia B,' 'inhibitors,' 'immune tolerance induction,' 'bypassing agents,' 'emicizumab,' 'concizumab,' 'marstacimab,' 'fitusiran,' and 'gene therapy.' Relevant clinical trials, observational studies, guidelines, and review articles were evaluated. Despite transformative progress, important unmet needs remain, including incomplete hemostatic control, lack of predictive biomarkers, limited laboratory standardization, and inequitable global access. Future advances will depend on biomarker-guided personalized therapy, rational combination strategies, and integration of immune-modulatory and gene-based approaches to achieve durable tolerance and potentially curative outcomes."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Preventive care • Rare Diseases

Descriptive Comparison of Bleeding Outcomes with Emicizumab and Concizumab Prophylaxis in Hemophilia A with Inhibitors: Analysis of HAVEN-1 and EXPLORER-7 PACO Data (ISTH 2026) - "The choice between treatments should consider additional factors such as safety profile, dosing regimen, patient preferences, and availability. Table or Figure Upload (1) Table 1 Page 2 Table or Figure Upload (2) Any DOI*10.1016/j.rpth.2026.104862"

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Association Between Bone Marrow Edema and Joint Pain in Haemophilic Arthropathy: A Retrospective Single-Center Study (ISTH 2026) - "Home therapy was heterogeneous: FVIII standard (48.6%), FVIII EHL (8.6%), FIX EHL (11.4%), Emicizumab (14.3%), Concizumab (2.9%), DDAVP (5%) and other regimens. These findings suggest that BME contributes to symptomatic arthropathy. Prospective studies are needed to clarify the clinical and prognostic significance of BME in persons with hemophilia DOI*10.1016/j.rpth.2026.105934"

Retrospective data • Hematological Disorders • Hemophilia • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rare Diseases • Rheumatology

IN VITRO THROMBIN GENERATION IN CONCIZUMAB COMBINATION THERAPY (ISTH 2026) - "Samples were spiked in vitro with concizumab (400 or 4000 ng/mL) alone or combinationed with emicizumab (10 or 50 μg/mL), efanesoctocog alfa (0.05, 0.5, or-1 IU/mL), rFVIIa (1 µg/mL), or aPCC (0.5 IU/mL). Grey regions indicate normal ranges. DOI*10.1016/j.rpth.2026.104865"

Combination therapy • Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Pediatric hemophilia management: A cross-sectional study at a single tertiary public center in Argentina. (ISTH 2026) - "Since 2019, CwSHA with inhibitors have received emicizumab without immune tolerance induction(ITI)...CwSHB with concizumab showed a marked ABR reduction, from 10 to 0 and 26 to 6, respectively, recovering normal physical activity...A high prevalence of inhibitors was observed in CwSHA, probably linked with early and severe bleeding events. Table or Figure Upload (1) Page 2 Table or Figure Upload (2) DOI*10.1016/j.rpth.2026.104861"

Clinical • Observational data • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • Rare Diseases

...Novo Nordisk is also presenting first-time results from the phase 3 open-label concizumab explorer10 trial evaluating the efficacy and safety of concizumab prophylaxis in 24 children below the age of 12 living with hemophilia A or B with inhibitors. (Novo Nordisk Press Release) - "In the trial, the estimated mean ABR on concizumab prophylaxis was 2.08 (95% CI 1.27, 3.41) compared to 11.51 (95% CI 7.75, 17.09) for previous on-demand treatment and the ABR ratio was 0.18 (95% CI 0.11, 0.29), representing an 82% reduction in ABR with concizumab compared to prior on-demand treatment. Eighty-three percent of the participants reported at least one on-treatment adverse event. Most events were mild in severity (152 out of 192 events) and with reported outcome as recovered (178 out of 192 events). Injection site reactions were infrequent, with 0.1 events per patient years of exposure. Twenty-nine percent of the participants reported serious adverse events."

P3 data • Hemophilia A • Hemophilia B

Presentation Theater 5 Everyday Protection with Concizumab (Alhemo®): Redefining Precision and Control in Haemophilia B (ISTH 2026) - "Sponsored by Novo Nordisk Healthcare AG"

Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Novel Therapeutic Approaches in BDUC: Concizumab as a Potential Treatment Option (ISTH 2026) - No abstract available

Cardiovascular • Hematological Disorders • Thrombosis • Women's Health

The impact of TFPI inhibition on procoagulant platelet-dependent thrombin generation in hemophilia A (ISTH 2026) - "The TFPI inhibitor concizumab (1000 ng/mL) was added ex vivo...Given the associated increase in procoagulant activity, careful monitoring for thrombotic risk, particularly in patients with cardiovascular comorbidities, remains essential. DOI*10.1016/j.rpth.2026.104851"

Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Pharmacokinetic Variability and Dosing Strategy Heterogeneity in Anti‑TFPI Therapies: Implications for Plasma Monitoring (ISTH 2026) - "Aims To explore inter-patient PK variability between marstacimab and concizumab in patients WITHOUT inhibitors, evaluate dose adjustment requirements, and assess whether PK variability characteristics support the rationale for plasma monitoring in anti ‑ TFPI therapies. These observations are hypothesis ‑ generating and warrant prospective validation. Table or Figure Upload (1) Table 1 Page 2 Table or Figure Upload (2) Table 2 DOI*10.1016/j.rpth.2026.104814"

Heterogeneity • PK/PD data • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Thrombin Generation Assay as a useful Tool to evaluate Anti-TFPI Therapy in patient with severe Hemophilia B with Inhibitors and Comorbidities (ISTH 2026) - "Methods A 37-year-old patient with sHBwI (inhibitor titer 1–185 BU), obesity (BMI 34 kg/m²), 5 target joints and hypertension received befovacimab (150 mg/week) for 7 months (M) followed by concizumab (0.2 mg/kg/day and 0.15 mg/kg/day) for 19M. M = months Page 2 Table or Figure Upload (2) Table 2: Biological parameters during Befovacimab therapy. M = months Page 3 DOI*10.1016/j.rpth.2026.104883"

Clinical • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia B • Hypertension • Obesity • Osteoarthritis • Rare Diseases

An in vitro study of the effects of concizumab on different coagulation assays (ISTH 2026) - "Page 2 Table or Figure Upload (2) Figure 2: Correlation between concizumab concentration and tLag (panel A) and ETP (panel B) results. Page 3 DOI*10.1016/j.rpth.2026.104895"

Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Immunology • Inflammatory Arthritis • Rare Diseases • PROS1

Marstacimab versus Concizumab in Hemophilia A/B Without Inhibitors: A Descriptive Comparison of Pivotal Trials (ISTH 2026) - "With comparable final ABR despite heterogeneous trial designs, treatment choice between anti-TFPI agents should prioritize patient-specific thrombotic risk, dosing preference, and monitoring capacity rather than cross-trial efficacy contrasts. Active thrombotic surveillance remains essential for both therapies Table or Figure Upload (1) Page 2 Table or Figure Upload (2) Page 3 DOI*10.1016/j.rpth.2026.104872"

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Association of Concizumab with Tissue Factor Pathway Inhibitor (TFPI) within Platelets and the Extracellular Matrix (ECM) (ISTH 2026) - "Further, concizumab diffuses within extravascular spaces where it binds to TFPIα within ECM surrounding blood vessels. The binding of concizumab to TFPI at sites within and outside the vasculature likely contribute to its efficacy as a prophylactic treatment for hemophilia A and B. DOI*10.1016/j.rpth.2026.104824"

Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Mechanism-based functional monitoring of concizumab focusing on coagulation initiation: from comprehensive global assays to TFPI-oriented assessment (ISTH 2026) - "In contrast, SMAT-TFPI provides sensitive, mechanism-aligned functional assessment of concizumab, particularly within clinically critical low-nanomolar ranges. Table or Figure Upload (1) Page 2 DOI*10.1016/j.rpth.2026.104300"

Clinical • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • Thrombosis

Concizumab prophylaxis in paediatric participants with haemophilia A/B with inhibitors in the phase 3 explorer10 study: Efficacy, safety and PK/PD results from the 32-week cut-off (ISTH 2026) - P3 | "The safety profile is consistent with previous observations. Table or Figure Upload (1) Table or Figure Upload (2) Page 3 DOI*10.1016/j.rpth.2026.103469"

Clinical • P3 data • PK/PD data • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • Rare Diseases

Anti-TFPI Single-Domain Antibodies: Novel Rebalancing Therapies for Hemophilia and Other Rare Bleeding Disorders. (PubMed, Thromb Haemost) - "As such, anti-TFPI monoclonal antibodies such as concizumab have been developed to treat hemophilia A (HA) and B (HB).The objective of this study is to generate single-domain antibodies (sdAbs) as a novel class of pharmacological agents blocking TFPI and increasing thrombin generation in the plasma of patients with severe HA, HB, and FXI deficiency.A large synthetic library of sdAbs was generated and selected by phage-display on recombinant human TFPIα (rhTFPIα)...Both sdAbs impaired the ability of rhTFPIα to inhibit FXa and TF/FVIIa, in the absence and presence of their physiological modulators (protein S and FXa, respectively). These sdAbs efficiently increased thrombin generation in HB and FXI-deficient plasmas.Our large synthetic library could be used for readily generating diverse and functionally relevant anti-TFPI sdAbs that may be therapeutically attractive."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • PROS1

Novo Nordisk to showcase new data across its haemophilia portfolio at the ISTH Congress 2026, featuring investigational denecimig (Novo Nordisk Press Release) - "The broad range of oral and poster presentations spans the Novo Nordisk haemophilia portfolio and is highlighted by multiple analyses of the phase 3 FRONTIER4 study evaluating the long-term efficacy and safety of investigational denecimig (Mim8) across a range of age groups and dosing frequencies, including once-monthly, once-every-two-weeks, and once-weekly prophylaxis. Additional insights from the portfolio will span clinical and real-world treatment data as well as patient-reported outcomes....Additionally, data from the open-label phase 3 explorer10 study will be presented for the first time, evaluating the efficacy and safety of concizumab in children up to 11 years of age living with haemophilia A or B (HA/HB), with inhibitors."

Clinical data • P3 data • Patient reported outcomes • Preclinical • Hemophilia A • Hemophilia B