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

Non-clotting factor therapies for preventing bleeds in people with congenital hemophilia A or B. (PubMed, Cochrane Database Syst Rev) - "Evidence from RCTs shows that prophylaxis using non-clotting factor therapies compared with on-demand treatment may reduce bleeding events, increase the percentage of individuals with zero bleeds, increase the incidence of non-serious adverse events, and improve HRQoL. Comparative assessments with other prophylaxis regimens, assessment of long-term joint outcomes, and assessment of economic outcomes will improve evidence-based decision-making for the use of these therapies in bleed prevention."

Clinical • Journal • Review • Cystic Fibrosis • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Immunology • Oncology • Pain • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Non-joint bleeds in patients with hemophilia A or B with inhibitors: Concizumab explorer7 study (THSNA 2026) - P3 | "Few non-joint bleeds were reported with concizumab prophylaxis in explorer7 at the 32- and 56-week cut-offs. The ABR for muscle bleeding episodes was reduced in patients on concizumab compared with on-demand treatment. Previously presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress, Washington, DC, USA, 21-25 June 2025."

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

Concizumab Efficacy in Patients With Hemophilia A/B Without Inhibitors from the Phase 3 explorer8 Study: A Post-hoc Sensitivity Analysis for the Intra-patient Comparison of Concizumab With Previous Prophylaxis (THSNA 2026) - P3 | "Post-hoc sensitivity analyses using imputed data for the three patients in the explorer8 intra-patient comparison subset who had extreme ABRs showed that the upper limit of the 95% CI of the ABR ratios decreased below the non-inferiority margin of 2.0 when comparing concizumab to previous prophylaxis. This indicates that, for most patients, ABRs during concizumab demonstrated non-inferiority when compared to prior prophylaxis regimens. As with any therapy, there may be variability in individual responses to treatment."

Clinical • P3 data • Retrospective data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Comparative Efficacy and Safety of Non-Clotting Factor Prophylaxis Versus. on-Demand Therapy in Hemophilia: A Meta-Analysis of Randomized Controlled Trials. (PubMed, Clin Appl Thromb Hemost) - "Prophylaxis increased the likelihood of achieving zero treated bleeds [RR = 4.11; 95% CI: (1.48%, 11.45%), I2 = 88.5%, p < 0.0001]. An exploratory network meta-analysis comparing fitusiran, emicizumab, and concizumab reported no statistically significant difference in the ABR for all treated bleeds.ConclusionCompared to on-demand therapy, non-factor prophylactic therapies significantly reduce bleeding episodes, improve quality of life, and increase the likelihood of zero bleeds in patients with hemophilia."

Journal • Retrospective data • Review • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Challenges in Balancing Hemostasis and Thrombosis in Therapy Tailoring for Hemophilia: A Narrative Review. (PubMed, Int J Mol Sci) - "Therapeutic approaches, including innovative NRTs, such as emicizumab, or rebalancing agents (e.g., concizumab, marstacimab, fitusiran), offer promising advancements in bleeding prophylaxis but may increase thrombotic risks. FXI inhibition emerges as a paradigm shift in thrombosis management, offering reduced bleeding risks while preserving vascular health. Finally, this review highlights the need for global laboratory assays to personalize treatments, emphasizing strategies to optimize safety and efficacy, particularly as hemophilia patients live longer with complex comorbidity profiles."

Journal • Review • Acute Coronary Syndrome • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Human Immunodeficiency Virus • Infectious Disease • Rare Diseases • Thrombosis

Investigation of the Suitability of the ROTEM Assay to Measure Coagulation Potential in Blood From Patients on Concizumab Prophylaxis. (PubMed, Haemophilia) - "Due to the poor correlation between ROTEM parameters, concizumab exposure, free TFPI and thrombin generation parameters and the lack of consistent and reliable performance of the modified ROTEM assay, it cannot be recommended for general monitoring of patients on concizumab prophylaxis."

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

Concizumab in hemophilia with inhibitors: Longer-term efficacy and safety results from the phase 3 explorer7 study. (PubMed, Blood Adv) - P3 | "Longer‑term (≥1 year) efficacy and safety results of concizumab prophylaxis for HAwI/HBwI were consistent with the 32-week cut-off results in explorer7. ClinicalTrials.gov; NCT04083781."

Journal • P3 data • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Concizumab for Hemophilia A and Hemophilia B (ASH 2025) - No abstract available

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

Efficacy, quality of life, and safety of non-clotting factor prophylaxis in Hemophilia A and b: A meta-analysis across inhibitor status (ASH 2025) - "Eligible studies included double-arm randomized controlled trials (RCTs) comparing non-clotting factor prophylaxis (emicizumab, fitusiran, or concizumab) with on-demand treatment in patients with hemophilia A or B, regardless of inhibitor status. Compared to on-demand therapy, non-factor prophylactic therapies significantly reduce bleeding episodes, improve quality of life, and increase the likelihood of zero bleeds in patients with hemophilia. Although associated with a higher rate of adverse events, the therapies themselves did not increase the risk of serious adverse events. While efficacy outcomes were similar across agents, cost differences may influence treatment selection.These findings support the clinical utilization of non-factor prophylaxis in managing hemophilia A and B, regardless of inhibitor status."

HEOR • Retrospective data • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Immunogenicity assessment of concizumab in patients with Hemophilia A and b: Assays developed to measure anti-drug antibodies and integrated results from clinical trials (ASH 2025) - "To date, a favorableimmunogenicity profile has been observed during the concizumab ph2/3 clinical trials with no apparentimpact of ADAs on efficacy, safety or PK/PD using the validated bADA and nAb assays. Based on thepresented integrated analysis of bADAs with PK/PD, the nAb assays may be considered redundant for theinterpretation of overall immunogenicity findings."

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

Concizumab plasma concentration measurements for personalized dose adjustment in patients with Hemophilia A/B with and without inhibitors: Data from the Phase 3 explorer7 and explorer8 studies (ASH 2025) - P3 | "After dose adjustment to 0.15 mg/kg, the mean concizumab plasma concentrationdecreased from 5,525 ng/mL to 766 ng/mL from week 4 to week 12. Mean ABR in the 4,000 ng/mL plasma concizumab, observed mean ABR after dose adjustment was 3.8(SD: 4.8; mean observation period 340 days), similar to the 200–4,000 ng/mL group (3.1; SD: 6.5; meanobservation period 287 days).ConclusionsThese findings support the use of concizumab plasma concentration-guided dose adjustments tooptimize prophylaxis in patients with hemophilia A or B, with or without inhibitors. Exposure-responseanalyses confirmed the validity of the selected lower (200 ng/mL) and upper (4,000 ng/mL) limits ofconcizumab plasma concentration and showed that dose adjustments can effectively personalize therapyto reduce bleeding rates."

Clinical • P3 data • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Real‑world experience with anti‑TFPI agent (Marstacimab) in severe and non‑severe hemophilia: First reported successful use in a female with non-severe hemophilia b (ASH 2025) - "Recent approval of rebalancing agents—includingMarstacimab, a tissue factor pathway inhibitor (TFPI) monoclonal antibody for people with hemophilia Aand B without inhibitors, along with Fitusiran and Concizumab—herald a new era of expanded, andeffective patient-friendly therapeutic options.To date, regulatory approvals and pivotal trials have focused predominantly on severe hemophilia (factorVIII or IX activity <1%), often excluding non-severe (1–5% activity) and female pwh...50% switchedfrom a CFC based prophylaxis while the remaining switched to weekly SQ regimen from on demandtherapy in the moderate cohort whereas 75% of severe Hemophilia A/B patients switched from CFC andremaining from previous Emicizumab prophylaxis... Our findings underscore the critical need to consider bleeding phenotype—not merely factorlevels—when selecting candidates for rebalancing therapies. Women with hemophilia endure recurrent,debilitating bleeds related to menorrhagia or obstetric..."

Clinical • Real-world • Real-world evidence • Cardiovascular • Gynecology • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Musculoskeletal Diseases • Obstetrics • Rare Diseases • Rheumatology

Developing prediction rules to safely decrease unnecessary head CT scans for pediatric patients with hemophilia presenting with head injuries (ASH 2025) - "Among those, 50 of 103 (48.5%) were on non-factor therapy (e.g., emicizumab or concizumab), 10 of 103 (9.7%) were on extended half-life (EHL) factor, and 43 of 103 (41.7%) were on standard half-life (SHL) factor. Risk stratification for ICH or ciTBI in pediatric PwH after head injury remains inadequately addressed. Ourpreliminary data suggest that the PECARN tool is a promising starting point to safely reduce unnecessaryCT scans in this population. Additionally, prophylaxis class and inhibitor status may be important factorsin future risk stratification models."

Clinical • Brain Cancer • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases • Solid Tumor • Vascular Neurology

Factor v inhibits factor x activation by the tissue factor-factor VIIa complex (ASH 2025) - "In someexperiments, concizumab (4 µg/mL, NovoNordisk) was added to the plasma to block TFPIα or antibodiesagainst FV's light and heavy chains (Prolytix, AHV-5101, AHV-5146)... These data support a new anticoagulant role of FV wherein it inhibits FX activation byTF:FVIIa during the initiation of coagulation, independent of TFPIα. FV reduces the rate and extent ofthrombin generation, an effect that is attenuated at normal FVIII levels, suggesting complementary FXactivation by intrinsic tenase (FVIIIa:FIXa). Coagulation initiated by the contact pathway via kaolin does notshow the same trends."

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

Concizumab efficacy in patients with Hemophilia A/B without inhibitors from the Phase 3 explorer8 study: A post-hoc sensitivity analysis for the intra-patient comparison of concizumab with previous prophylaxis (ASH 2025) - P3 | "As with any therapy, there may be some variability inindividual responses to treatment. Overall, the phase 3 explorer8 study showed that once-daily,subcutaneous concizumab prophylaxis was efficacious and well-tolerated."

Clinical • P3 data • Retrospective data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

fss25-110: Advancing Hemophilia Care—Uniting Expert Insights and Community Voices to Shape the Future of Non-Factor Replacement Therapy (ASH 2025) - "This dynamic event combines expert panel discussions, real-world case challenges, and insights from patients and community HCPs to explore the latest data on novel therapies including fitusiran, concizumab, marstacimab, and Mim8. Through interactive polling and audience Q&A, attendees will gain practical guidance on integrating these therapies into personalized care strategies for patients with moderate to severe hemophilia A and B. Discover how to navigate evolving safety profiles, improve joint health outcomes, and tailor treatment based on patient needs and preferences. This symposium offers a comprehensive view of current challenges, cutting-edge solutions, and future directions in hemophilia management, equipping you with actionable insights to improve clinical practice."

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

Gene Therapy and Hemophilia A: What Is the Future of Curative Therapy in the Age of Emicizumab? (ASH 2024) - "Additionally, the beneficial results seen in hemophilia A gene therapy clinical trials have occurred with meaningful challenges. This talk will review the risks and benefits of gene therapy for hemophilia A and consider them within the context of therapies (emicizumab and Fc-VWF-XTEN fusion protein-eht) that have shown consistent benefit compared with previously available factor VIII products as well as other promising therapies (Mim8, fitusiran, concizumab, and marstacimab) in late-stage clinical trials."

Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Patient and Clinical Experience on Concizumab Clinical Trial: A Case Study (ASH 2024) - P=N/A, P3 | "The maintenance dose was initiated on week 4 based on a concizumab exposure of 97.9 ng/mL.Prior to explorer8, the patient was intensely treated with daily BeneFIX® and Rebinyn® prophylaxis during explorer6, but both FIX standard and extended half-life treatment failed to prevent bleeding episodes.Key Clinical Question : What factors should be considered when determining whether a patient should be withdrawn from a clinical trial?Clinical Approach : Throughout the clinical trial, the investigator discussed withdrawal from the study because of an increase in the number of bleeding episodes; however, the patient remained in the clinical trial as the patient and their family preferred concizumab over previous prophylaxis regimens. This case demonstrates that we may have more to learn from our patients on why they choose to participate and/or stay on clinical trials.Disclaimer : Novo Nordisk had no influence on the content of the ABSTRACT . The studies..."

Case study • Clinical • Hematological Disorders • Hemophilia • Hemophilia B • Infectious Disease • Novel Coronavirus Disease • Rare Diseases

Efficacy and Safety of Concizumab Prophylaxis in Patients with Hemophilia A or B without Inhibitors: 56-Week Cut-Off Results of the Phase 3 explorer8 Study (ASH 2023) - P3 | "Conclusions Concizumab prophylaxis showed longer-term (≥1 year) efficacy in adult and adolescent patients with HA/HB at the 56-week cut-off, which was consistent with the results observed at CACO. Concizumab prophylaxis was considered safe and well tolerated in patients with HA/HB."

Clinical • P3 data • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Immunology • Rare Diseases

The Effect of Concizumab Prophylaxis on Target Joints, Resolution and Joint Bleeds in Patients With Hemophilia A or B With or Without Inhibitors in Phase 3 Clinical Trials (ASH 2023) - P3 | "Once-daily, subcutaneous concizumab prophylaxis resolved 86.3% of target joints in patients with HA or HB, and 91.8% of target joints in patients with HAwI or HBwI, most patients within 12.0 months. The median ABRs for treated spontaneous and traumatic target joint bleeding episodes at 56 weeks for both patients with HA or HB and HAwI or HBwI were 0.0."

Clinical • P3 data • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • Rheumatology

Surgical Procedures and Hemostatic Outcome in Patients with Hemophilia Receiving Concizumab Prophylaxis during the Phase 3 explorer7 and explorer8 Trials (ASH 2023) - P3 | "Most minor surgeries that took place were dental procedures and the majority of surgical-related bleeding episodes were mild or moderate. Overall, minor surgeries could be performed on patients with hemophilia under concizumab prophylaxis."

Clinical • P3 data • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Musculoskeletal Diseases • Orthopedics • Rare Diseases • Rheumatology

Comparison of Drugs Used for Prophylaxis in Hemophilia a or B with Inhibitors: A Systematic Review and Frequentist Network Meta-Analysis of Randomized Clinical Trials (ASH 2024) - "NMA was registered on PROSPERO CRD42024532136.Results : In 6 RCTs (N=457), 38 patients were treated with fitusiran prophylaxis, 114 patients with concizumab prophylaxis, 147 patients with emicizumab prophylaxis, 17 patients with FEIBA NF prophylaxis, 26 patients with AICC prophylaxis, and 115 patients were only treated on demand without prophylaxis. Emicizumab and fitusiran had higher efficacy as compared to other prophylactic agents in hemophilia. More large-scale randomized head-to-head comparisons are needed to confirm these results."

Retrospective data • Review • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Concizumab As a Possible Treatment for Bleeding Disordersof Unknown Cause (ASH 2024) - "There are few studies on the management of bleeding in BDUC and most relate to the use of tranexamic acid (Baker et al, J Thromb Haemost. In these cases, concizumab at concentrations similar to the trough plasma levels observed in haemophilia clinical trials (350-550 ng/ml, Matsushita T et al, N Engl J Med. 2023 Aug 31; 389(9) : 783-794) and rFVIIa emerge as potential therapeutic alternatives for these patients."

Hematological Disorders • Hemophilia • Rare Diseases

Low Normal Levels of Factor V Enhance Thrombin Generation in Hemophilia a in a Tissue Factor Pathway Inhibitor Independent Manner (ASH 2024) - "In some experiments, concizumab (4 µg/mL, NovoNordisk) and/or anti-A2 and anti-C2 FVIII function blocking antibodies (GMA-8015, GMA-8006, Green Mountain Antibodies) were added to the plasma...Results from FXa initiated thrombin generation suggest this effect occurs upstream of the common pathway. FVa does inhibit activation of FX by TF : FVIIa (Al Dieri, JTH, 2013), thus lower FV may result in reduced inhibition of the initiation of coagulation, a phenomenon that appears to become more prominent in hemophilia A plasma."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Annualized Bleeding Rates in Patients with Hemophilia a or B and Inhibitors with and without Target Joints at Baseline: Results from the Concizumab Phase 3 Explorer7 Study (ASH 2024) - P3 | "Overall safety data showed no new findings. Conclusion In the explorer7 study, once-daily, subcutaneous concizumab prophylaxis effectively reduced ABR irrespective of the presence of target joints at baseline at the 32-week cut-off, and low ABRs were maintained at the 56-week cut-off."

Clinical • P3 data • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • Rheumatology