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

Concizumab prophylaxis in people with hemophilia A or B without inhibitors: patient-reported outcome results from the phase 3 explorer8 study. (PubMed, Res Pract Thromb Haemost) - P3 | "Estimated treatment difference at week 24 between patients in arms 1 and 2 was -18.0 points (95% CI, -26.4 to -9.5) for Haemophilia Quality of Life Questionnaire for Adults "total score" and -16.8 points (95% CI, -32.2 to -1.4) for "physical health." Hemophilia Treatment Experience Measure and Haemophilia Patient Preference Questionnaire results favored concizumab prophylaxis over no prophylaxis or previous treatment. PRO data from the phase 3 explorer8 study provided additional support for concizumab prophylaxis compared with no prophylaxis as a treatment option for patients with HA/HB."

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

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

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

CDSCO Approves Novo Nordisk Protocol Amendment Proposal For Concizumab Study (Medical Dialogues) - "The Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has approved the protocol amendment proposal presented by Novo Nordisk to study Concizumab in patients with hemophilia A or B with inhibitors...This came after Novo Nordisk presented protocol amendment version 11.0 dated 07 October 2024 protocol no. NN7415-4311 (EXPLORER 7)....After detailed deliberation, the committee recommended the approval of the protocol amendment as presented by the firm."

Clinical protocol • 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=90 | Recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Dec 2024 ➔ Jun 2026

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

High-quality standardised ELISA to manage dose adjustments during concizumab prophylaxis in patients with haemophilia A/B with and without inhibitors in the routine clinical setting: Test access model description (EAHAD 2025) - No abstract available

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

Efficacy and safety of concizumab prophylaxis in patients with haemophilia and inhibitors: Results from the Early Access Program in France (EAHAD 2025) - No abstract available

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Annualised Bleeding Rates in Patients with Haemophilia A or B and Inhibitors with and without Target Joints at Baseline: Results from the Concizumab Phase 3 explorer7 Study (EAHAD 2025) - No abstract available

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

Advances in Development of Drug Treatment for Hemophilia with Inhibitors. (PubMed, ACS Pharmacol Transl Sci) - "More recently, emicizumab, a bispecific antibody that mimics the function of activated clotting factor VIII, has demonstrated favorable efficacy for prophylaxis in patients with hemophilia A and inhibitors, representing a promising new therapeutic strategy...This review summarizes the current understanding of the pathophysiology of inhibitor development in hemophilia, outlines existing treatment options, and discusses advancements in novel therapeutic biologics, including a recombinant activated clotting factor VII variant (marzeptacog alfa), a new bispecific antibody (Mim8), antitissue factor pathway inhibitor antibodies (concizumab and marstacimab), and small interfering RNA targeting antithrombin (fitusiran). All of these agents are administered subcutaneously, with some offering the convenience of less frequent dosing (e.g., weekly or monthly). These potential drug candidates may provide significant benefits for the prophylaxis or treatment of bleeding disorders in..."

Journal • Review • 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

FDA approves Alhemo injection 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 with inhibitors (PRNewswire) - "Novo Nordisk announced today that the U.S. 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 with inhibitors, continuing its more than 35-year commitment to those living with rare bleeding disorders. Alhemo is a tissue factor pathway inhibitor (TFPI) antagonist that is dosed in a prefilled, premixed pen for subcutaneous injection (60 mg/1.5 mL, 150 mg/1.5 mL, or 300 mg/3 mL) via a thin 32 gauge, 4 mm needle, which is provided separately....FDA approval is based on data from the pivotal phase 3 trial (explorer7) establishing the safety and efficacy of Alhemo for daily prevention of bleeds in adults and pediatric patients 12 years of age and older living with hemophilia A or B with inhibitors."

FDA approval • Hemophilia • Hemophilia B

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

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

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

Novo Nordisk to present new data from sickle cell disease and haemophilia trials at the 66th American Society of Hematology (ASH) annual meeting (GlobeNewswire) - "Novo Nordisk today announced the presentation of 13 abstracts, three of which will be presented in oral sessions...which will take place from 7 to 10 December 2024 in San Diego, California....From Novo Nordisk’s haemophilia portfolio, there are two oral presentations of note: first on the efficacy and safety results of an interim analysis from FRONTIER4, a phase 3 open-label, multi-centre extension study of Mim8 in people living with haemophilia A with and without inhibitors (HA/HAwI). Additionally, an oral presentation of data from the phase 3 explorer7 study assessing the efficacy of concizumab in people with haemophilia A or B with inhibitors (HAwI/HBwI), with or without recurring bleeds into the same joint (or target joints) at baseline."

P3 data • Genetic Disorders • Hemophilia • Hemophilia B

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

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 prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial. (PubMed, Lancet Haematol) - P=N/A, P2, P3 | "Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors."

Clinical • Journal • P3 data • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Hypertension • Infectious Disease • Novel Coronavirus Disease • Rare Diseases • Respiratory Diseases

Non-factor Therapies for Hemophilia: Achievements and Perspectives. (PubMed, Semin Thromb Hemost) - "Factor VIII (FVIII)-mimetic agents, such as emicizumab, have transformed the management of hemophilia A with inhibitors, offering a lower treatment burden and an effective alternative for those without inhibitors as well. Rebalancing agents, including anti-tissular factor pathway inhibitor agents (concizumab and marstacimab) and serpin inhibitors like fitusiran, have shown promising efficacy for patients with hemophilia B with inhibitors and other hemophilia subtypes...Unresolved issues include optimal management strategies for major surgeries and tailored approaches for safe use in older populations. This review highlights the progress and future potential of NFTs in treating persons with hemophilia."

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

In Vitro Correction of Thrombin Generation by Concizumab (Anti-TFPI) for Severe Hemophilia Patients (clinicaltrials.gov) - P=N/A | N=20 | Completed | Sponsor: Centre Hospitalier Universitaire de Saint Etienne | Recruiting ➔ Completed

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

Examining Downstream Effects of Concizumab in Hemophilia A with a Mathematical Modeling Approach. (PubMed, J Thromb Haemost) - "The effectiveness of concizumab is mediated through blockade of TFPI anticoagulant activities in plasma and on multiple physiological surfaces. An important and previously unrecognized function of concizumab was sequestration of plasma TFPIα to the endothelium."

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

CDSCO Panel Grants Novo Nordisk Protocol Amendment Proposal To Study Concizumab (Medical Dialogues) - "Recommending to increase the number of subjects from 15 to 35, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has approved the protocol amendment proposal presented by Novo Nordisk to study the efficacy, safety, and pharmacokinetics of concizumab prophylaxis in children below 12 years with hemophilia A or B with or without inhibitors. This came after the firm presented protocol amendment version 2.0 dated 06 October 2023 protocol no. NN7415-4616 and increased the number of subjects from India. This is an open-label study investigating the efficacy, safety, and pharmacokinetics of concizumab prophylaxis in children below 12 years with hemophilia A or B with or without inhibitors."

Clinical protocol • New trial • Genetic Disorders • Hemophilia • Hemophilia B

Novo Nordisk A/S: Alhemo recommended for European approval as first once-daily subcutaneous prophylactic treatment for people living with haemophilia A or B with inhibitors (GlobeNewswire) - "Novo Nordisk today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending approval of Alhemo (concizumab) as the first once-daily subcutaneous prophylactic treatment for people aged 12 years or older living with haemophilia A or B with inhibitors....The CHMP positive opinion is based on data from the phase 3 explorer7 study..."

CHMP • Genetic Disorders • Hemophilia • Hemophilia B

Antibodies to watch in 2024. (PubMed, MAbs) - "In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi))...These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa)...Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates..."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

explorer7: Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia With Inhibitors (clinicaltrials.gov) - P3 | N=136 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial completion date: Dec 2025 ➔ Feb 2027

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

The Concizumab Pen-Injector is Easy to Use and Preferred by Hemophilia Patients and Caregivers: A Usability Study Assessing Pen-Injector Handling and Preference. (PubMed, Patient Prefer Adherence) - "This preference and handling study was conducted in accordance with authority guidelines for approval of new devices and included adults and adolescents with HA/HB with or without inhibitors and caregivers currently administering factor replacement therapy or factor VIII mimetic (emicizumab) therapy. 88% of participants preferred the pen-injector (n=70; 95% CI 78-94%) over their current injection system, and 9% (n=7) reported "no preference". Participants found the concizumab pen-injector easy to learn and easy to use and preferred it over their current injection systems."

Journal • Hematological Disorders • Hemophilia • Rare Diseases