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

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

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 • Anemia • Cardiovascular • Gynecology • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Musculoskeletal Diseases • Obstetrics • Rare Diseases • Rheumatology

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

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

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

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

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

Alhemo's FDA approval: a new treatment option for Hemophilia A & B. (PubMed, Ann Med Surg (Lond)) - No abstract available

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

Concizumab use in toddlers with haemophilia B and inhibitors real world data from an international collaboration. (PubMed, J Thromb Haemost) - "Concizumab appears safe and effective in young children with severe HB and inhibitors. It offers a promising, factor-free prophylactic strategy."

Journal • Real-world evidence • Allergy • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Concizumab approved to prevent or reduce the frequency of bleeding episodes in people aged 12 years and older with haemophilia A or B with inhibitors (GOV.UK)

MHRA approval • Hemophilia A • Hemophilia B

Explorer10: A Research Study on How Well Concizumab Works for You if You Have Haemophilia A or B With or Without Inhibitors (clinicaltrials.gov) - P3 | N=153 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Sep 2029 ➔ Apr 2026

Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Post-marketing Surveillance (Special Use-results Surveillance) on Treatment With Alhemo (clinicaltrials.gov) - P=N/A | N=30 | Enrolling by invitation | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Enrolling by invitation

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

Explorer10: A Research Study on How Well Concizumab Works for You if You Have Haemophilia A or B With or Without Inhibitors (clinicaltrials.gov) - P3 | N=153 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

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

Curative Therapies for Hemophilias and Hemoglobinopathies in Adults: Immune, Gene, and Stem Cell Approaches in a Global Context. (PubMed, Biomedicines) - "Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide."

Journal • Review • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Sickle Cell Disease • Transplantation

FDA approves Alhemo as once-daily prophylactic treatment to prevent or reduce the frequency of bleeding episodes for adults and children 12 years of age and older with hemophilia A or B (HA/HB) without inhibitors (PRNewswire) - "Novo Nordisk announced today that the US Food and Drug Administration (FDA) approved Alhemo (concizumab-mtci) injection as a once-daily prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or B (HA/HB) without inhibitors, expanding on the December 2024 approval for HA/HB with inhibitors....With this approval, Alhemo now offers a subcutaneous injection treatment option for this population....FDA approval is based on phase 3 trial data (explorer8), which established the safety and efficacy of Alhemo (concizumab-mtci) injection in people 12 years and older with hemophilia A or B (HA/HB) without inhibitors."

FDA approval • Hemophilia A • Hemophilia B

European regulatory authority adopts positive opinion for Novo Nordisk’s Alhemo (concizumab), recommending label expansion to treat haemophilia A and B without inhibitors (The Manila Times) - "Novo Nordisk today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending an update of the Alhemo (concizumab) label to include the treatment of severe haemophilia A and moderate or severe haemophilia B without inhibitors....The positive CHMP opinion is based on the results from the phase 3 explorer8 trial, which met its primary endpoint....Following the positive opinion from the CHMP, Novo Nordisk expects the European Commission (EC) to approve the label update within approximately two months."

CHMP • EMA approval • Hemophilia A • Hemophilia B

Rebalancing agents in hemophilia: knowns, unknowns, and uncertainties. (PubMed, Haematologica) - "Fitusiran is a small interfering RNA agent that reduces antithrombin synthesis in hepatocytes, favoring a procoagulant state. Other promising rebalancing agents are concizumab and marstacimab, which selectively bind to the K2 domain of the tissue factor pathway inhibitor, thus restoring thrombin generation. SerpinPC is a subcutaneous biological inhibitor that blocks the anticoagulant activated protein C pathway, while VGA039 is a monoclonal antibody that targets its cofactor protein S. Although the available clinical data are promising, several important challenges remain. These include the thrombotic risk of rebalancing agents, perioperative and bleeding management, availability in low-income countries, efficacy and FVIII equivalence compared to existing treatments, ideal target populations, and potential application in other hemostatic disorders. The primary aim of this review is to summarize the best available evidence on these novel rebalancing agents, while..."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Rebalancing therapy for congenital hemophilia (PubMed, Rinsho Ketsueki) - "The anti-TFPI agents concizumab and marstacimab are administered subcutaneously and have been approved for use in Japan. The siRNA drug fitusiran is used as an anti-AT agent that reduces the synthesis of AT, and SerpinPC as an anti-APC agent that specifically inhibits APC. This article will outline the concept of rebalancing therapy and the results of clinical trials, as well as precautions and potential issues during treatment."

Journal • Review • Hematological Disorders • Hemophilia • Rare Diseases

Fitusiran (Qfitlia) for hemophilia A and B. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Pharmacokinetic evaluation of concizumab for the treatment of hemophilia. (PubMed, Expert Opin Drug Metab Toxicol) - "While the daily injection may seem demanding, it does not compromise the optimal benefits of concizumab prophylaxis. Moreover, the acceptable safe profile and efficacy of concizumab in bleed prevention in hemophilia A or B with and without inhibitors provide reassurance that it may be a therapeutic option in managing all hemophilia patients."

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

PHYSICIANS OPTIMISTIC ABOUT NEXT EVOLUTION IN HEMOPHILIA PATIENT CARE (EHA 2025) - "Advancements in therapy are moving beyond factor replacement, with novel approaches such as gene therapy and non-factor therapies, including emicizumab, marstacimab, concizumab, fitusiran, and Mim8...The greatest challenges were cited as selecting the best treatment option (30%), patient adherence (28%) and securing insurance coverage (20%) - especially for newer options.45% of hematologists have made changes to the way they manage hemophilia A patients in the past year with more adoption of emicizumab and efanesoctocog alfa, for which they report high satisfaction... Managing hemophilia patients throughout their lifetime is challenging for hematologists as they aim to improve patient quality of life and lifestyle. Newer options are providing better efficacy for different patient types and with favorable administration. As these options are approved and launched, hematologists expect many patients will be candidates and they will quickly begin prescribing these agents as..."

Clinical • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Musculoskeletal Pain • Pain • Rare Diseases

TFPI slows prothombinase assembly when concizumab is bound to its second Kunitz domain (ISTH 2025) - "Concizumab reversed TFPIα inhibition of fully assembled FXa-FV’ prothrombinase. However, the TFPIα-concizumab complex retains some anticoagulant activity towards prothrombinase because the TFPIα C-terminal tail remains available to slow assembly of FXa and FV’ into prothrombinase. Methods Enzyme kinetic studies using 15nM TFPIα, 0.1nM FXa, 16nM FV, 1.4µM prothrombin, phospholipids, 2.5mM calcium and 5-100nM concizumab."

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

The effect of concizumab on thrombin generation in FVII deficient plasma (ISTH 2025) - "Similar data were obtained in normal human plasma where FVII activity was neutralized with antibodies. Table or Figure Upload"

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

Efficacy and convenience of concizumab prophylaxis in two patients affected by severe HAwI (ISTH 2025) - P3 | "Bleeding episodes required a total 351 mg rFVIIa, 100 mg for breakthrough bleedings and 251 mg for 2 surgeries. Table or Figure Upload"

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

Non-joint bleeds in patients with hemophilia A or B with inhibitors: Concizumab explorer7 study (ISTH 2025) - P3 | "At the 56-week cut-off (Table 1), low numbers of non-joint bleeds were maintained with concizumab. Table or Figure Upload"

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