Denecimig

Novo Nordisk has presented new long-term clinical data demonstrating the safety and efficacy of its investigational hemophilia A therapy, denecimig (Mim8), during the International Society on Thrombosis and Haemostasis (ISTH) Congress in Paris. The findings, from the ongoing Phase 3 FRONTIER4 extension study, showed sustained bleed protection and a favorable safety profile in children, adolescents and adults with hemophilia A, regardless of inhibitor status or dosing schedule. The interim analysis included 426 participants aged one year and older receiving denecimig prophylaxis through once-weekly, once-every-two-weeks or once-monthly dosing regimens. The study reported low rates of mild and transient injection-site reactions, with no clinical evidence of neutralizing antibodies. Efficacy outcomes remained consistent with previous FRONTIER studies. Estimated annualized bleeding rates were 0.75 among adults and adolescents and 0.37 among children. Approximately 71 percent of adults and adolescents and 89 percent of children experienced no treated bleeding episodes while receiving denecimig. Patient-reported outcomes also indicated sustained improvements in joint pain and reduced treatment burden across all dosing frequencies. Most participants reported that the denecimig pen injector was easy to use and quick to prepare and administer. Additional analyses from the Phase 3 FRONTIER2 and FRONTIER5 studies showed that denecimig restored thrombin generation to normal reference levels in adolescents and adults without triggering excessive clotting activity, further supporting its clinical profile. Novo Nordisk has already submitted a Biologics License Application (BLA) for denecimig to the US Food and Drug Administration, with regulatory review ongoing. The company also presented first-time results from the Phase 3 explorer10 study evaluating concizumab prophylaxis in children under 12 years of age with hemophilia A or B with inhibitors. The study demonstrated an estimated 82 percent reduction in annualized bleeding rates compared with previous on-demand treatment. While adverse events were common, most were mild, and injection-site reactions remained infrequent. Denecimig is an investigational bispecific antibody designed to mimic the function of Factor VIII, offering prophylactic treatment for hemophilia A with or without inhibitors. Concizumab, marketed as Alhemo in several countries for specific patient populations, is being investigated for expanded use in younger children. The new data add to the growing body of evidence supporting innovative prophylactic therapies aimed at improving long-term disease management and reducing treatment burden for people living with hemophilia.

Presented interim FRONTIER4 data evaluate the long-term safety and efficacy of investigational denecimig across once-weekly, once-every-two-weeks, and once-monthly dosing in hemophilia A participants of all ages and disease severities1,2 Denecimig is an investigational subcutaneous FVIIIa-mimetic antibody under review with the US Food and Drug Administration (FDA)1 Separate phase 3 explorer10 data observed that concizumab reduced annualized bleeding rate compared to on-demand treatment in children with hemophilia A or B, with inhibitors3 PLAINSBORO, N.J. and BAGSVÆRD, Denmark, July 11, 2026 /PRNewswire/ -- Novo Nordisk today unveiled new data from the phase 3 FRONTIER4 extension study evaluating the long-term safety and efficacy of investigational denecimig (Mim8) subcutaneous prophylaxis in children, adolescents, and adults with hemophilia A, with or without inhibitors, across a range of dosing frequencies including once-monthly, once-every-two-weeks, and once-weekly administration. These results and other data across Novo Nordisk's hemophilia portfolio were presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in Paris. "The positive safety and efficacy findings from FRONTIER4 reinforce denecimig's potential as a preventive treatment option for children, adolescents, and adults with hemophilia A, regardless of their inhibitor status or the dosing frequency used," said Dr. Martin Holst Lange, chief scientific officer and executive vice president, Research & Development at Novo Nordisk. "The breadth and totality of our data presented at ISTH reflect Novo Nordisk's commitment to advancing treatment innovation to address the diverse needs of people living with hemophilia." Interim analyses from the open-label, phase 3 FRONTIER4 long-term safety and efficacy study included 426 people with hemophilia A aged 1 year and older on denecimig prophylaxis (365 adults and adolescents with a median observation period of 0.50 years; 61 children with a median observation period of 0.33 years). For the primary study endpoint of safety, denecimig was found to be consistent with findings previously shared from the FRONTIER research program. Injection-site reactions (ISR) were reported at low rates in children (2.0% of injections) and in adolescents and adults (1.8% of injections), and all were mild and transient. No clinical evidence of neutralizing antibodies was observed. For the secondary study endpoints of efficacy, estimated mean annualized bleeding rates (ABRs) were consistent with findings from the FRONTIER research program across all dosing regimens and regardless of inhibitor status (ABRs: 0.75; 95% CI 0.60, 0.93 for adults and adolescents; 0.37; 95% CI 0.17, 0.76 for children). Across all doses, approximately 71% of adults and adolescents and 89% of children experienced zero treated bleeds while receiving denecimig.1,2 The interim assessment of exploratory patient-reported outcomes (PROs) from the long-term FRONTIER4 study showed findings from prior FRONTIER trials were maintained long-term in all dosing frequencies studied, including improved joint pain for people aged 12 and older (Joint Pain Rating Scale, JPRS) and reduced treatment burden for those aged one and older (Hemophilia Treatment Experience Measure, Hemo-TEM). Across all age groups and dosing frequencies, 94.1% of 185 participants found the denecimig pen-injector easy or very easy to use, and 89.7% found it quick or very quick to prepare and inject (Hemophilia Device Assessment Tool, HDAT).4 New post hoc analyses of participants aged 12 and older with available thrombin generation data from the phase 3 FRONTIER2 and FRONTIER5 studies found that denecimig prophylaxis increased thrombin generation, a measure of the body's ability to form clots, into the normal reference range in adolescents and adults without excessive response. These findings further support denecimig's data across the clinical program.5 In September 2025, Novo Nordisk submitted denecimig for review to the US Food and Drug Administration (FDA) through a Biologics License Application (BLA). "When managing a chronic condition like hemophilia A, it's important that treatments are evaluated over the long-term and also offer dosing optionality," said Guy Young, MD, Director, Hemostasis and Thrombosis Center at Children's Hospital, Los Angeles. "These data suggest denecimig, which has delivered consistent results across the entire FRONTIER program, has the potential to have a truly meaningful impact for a diverse array of people with hemophilia A." In addition to the latest denecimig data, 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. 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.3 About Hemophilia Hemophilia is a rare inherited bleeding disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding.6 While hemophilia can affect men and women, it's most common in men and is estimated to impact 1,125,000 men worldwide.7 There are different types of hemophilia, which are characterized by the type of clotting factor protein that is defective or missing. Hemophilia A is caused by a missing or defective clotting Factor VIII (FVIII), and hemophilia B is caused by a missing or defective clotting Factor IX (FIX).7 Hemophilia is often treated by replacing the missing clotting factor via intravenous infusions, also known as replacement therapy. However, sometimes the body can produce inhibitors as an immune response to the clotting factor replacement therapy. When this happens, the therapy may not work and can limit treatment options.6 About denecimig Denecimig is an investigational, bispecific antibody Factor VIIIa (FVIIIa) mimetic, designed as a routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults, adolescents, and children with hemophilia A (congenital FVIIIa deficiency), with or without inhibitors.8-12 Intended to be administered under the skin, denecimig bridges Factor IXa and Factor X.13 This action mimics FVIIIa function, which helps restore the body's thrombin generation capacity, helping blood to clot.14 About concizumab Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody designed to block a protein in the body that stops blood from clotting. By blocking TFPI, concizumab leads to downstream production of thrombin, which helps to clot the blood and to prevent or reduce the frequency of bleeding episodes.15 Concizumab is currently approved under the name Alhemo® in India, Brazil, and Switzerland for the treatment of adolescents and adults (12 years or older) with hemophilia A or B with inhibitors.16-18 In the US, Europe, Japan, and Australia, Alhemo® is currently approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adolescents and adults (12 years or older) with hemophilia A or B, with or without inhibitors.15, 19-21 It is not known if Alhemo® is safe and effective in people receiving ongoing immune tolerance induction or in children younger than 12 years of age. The use of concizumab in children below 12 years of age with hemophilia A or B, with or without inhibitors, is investigational, safety and efficacy are not established and concizumab is not approved by regulatory authorities or available anywhere in the world. About FRONTIER4 The FRONTIER clinical program investigates denecimig as a prophylaxis treatment for adults, adolescents, and children with hemophilia A, with or without inhibitors. The program includes FRONTIER1, FRONTIER2, FRONTIER3, FRONTIER4, and FRONTIER5.8-12 FRONTIER4 is the largest ongoing phase 3 trial of the FRONTIER program evaluating denecimig across all dosing frequencies in people of all ages, regardless of inhibitor status.8-12 The open-label trial aims to evaluate the long-term safety and efficacy of denecimig prophylaxis treatment in participants from across all FRONTIER trials who chose to continue on denecimig for the extension study.8 The FRONTIER4 long-term extension study includes 426 patients who decided to continue denecimig treatment after participating in the FRONTIER1, FRONTIER2, FRONTIER3, and FRONTIER5 studies. The current interim analysis covers a median observation period of 0.50 years in adults and adolescents and 0.33 years in children across the extension study, after patients have been in the pivotal phase 3 trials for a minimum of 26 to 52 weeks, depending on the FRONTIER trial they transitioned from.1,2,8-12 About FRONTIER2 The 52-week phase 3 FRONTIER2 study compared the efficacy and safety profile of once-monthly and once-weekly denecimig versus on-demand clotting factor treatment and versus prior coagulation factor prophylaxis treatment in people aged 12 and older living with hemophilia A, with or without inhibitors.10 About FRONTIER5 The 26-week phase 3 FRONTIER5 study investigated the safety of switching from emicizumab, an existing hemophilia A treatment, to denecimig without a washout period or loading dose. The safety of transitioning to denecimig was assessed for once-monthly, once-every-two-weeks and once-weekly dosing intervals in 48 participants who were treated with emicizumab prior to entering the study.12 About explorer10 Explorer10 is an ongoing, open-label phase 3 study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of concizumab prophylaxis in children under 12 years of age with hemophilia A or B, with or without inhibitors.3 About Novo Nordisk Novo Nordisk is a leading global healthcare company with a heritage of more than 100 years in diabetes care. Building on this foundation, our purpose is to drive change to defeat serious chronic diseases - from diabetes and obesity to rare blood and endocrine disorders - by pioneering scientific breakthroughs, expanding access to medicines, and working to prevent and ultimately cure disease. We are committed to long-term, responsible business practices that deliver financial, social, and environmental value. Headquartered in Denmark and operating in around 80 countries, Novo Nordisk employs approximately 67,900 people and markets products in roughly 170 countries. In the United States, Novo Nordisk has a 40-year presence, is headquartered in New Jersey, and employs approximately 10,000 people across more than 10 manufacturing, R&D, and corporate locations in seven states plus Washington, D.C. For more information, visit novonordisk.com and novonordisk-us.com, and follow us on Facebook, Instagram, X, LinkedIn, and YouTube. References Fernandez L, Oldenberg J, Mancuso M, et al. Mim8 (denecimig) prophylaxis in adults and adolescents with haemophilia A with or without inhibitors: Interim results from the FRONTIER4 long-term safety and efficacy study. Oral presentation presented at the Congress of the International Society on Thrombosis and Haemostasis 2026. July 11-15, 2026; Paris, France. Chitlur M, Fijnvandraat K, Frandsen I, et al. Mim8 (denecimig) prophylaxis in children with haemophilia A with or without inhibitors: Interim safety and efficacy results from the FRONTIER4 long-term extension study. Oral presentation presented at the Congress of the International Society on Thrombosis and Haemostasis 2026. July 11-15, 2026; Paris, France. Trakymienė S, Bhat R, Chan A, et al. 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. Oral presentation presented at the Congress of the International Society on Thrombosis and Haemostasis 2026. July 11-15, 2026; Paris, France. Ay C, Ahuja S, Chowdary P, et al. Mim8 (denecimig) prophylaxis in adults, adolescents and children with haemophilia A with or without inhibitors: Interim patient-reported outcomes from the long-term extension study (FRONTIER4). Poster presentation presented at the Congress of the International Society on Thrombosis and Haemostasis 2026. July 11-15, 2026; Paris, France. Young G, Peyvandi F, Dargaud Y, et al. Denecimig (Mim8) restores thrombin generation into the normal range in people with haemophilia A: Post hoc analysis of the phase 3 FRONTIER2, FRONTIER4, and FRONTIER5 studies. Poster presentation presented at the Congress of the International Society on Thrombosis and Haemostasis 2026. July 11-15, 2026; Paris, France. MedlinePlus. Hemophilia. Last accessed June 2026. Available at . Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020: 26(Suppl 6): 1-158. Clinicaltrials.gov. A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER 4). Last accessed June 2026. Available at: . ClinicalTrials.gov. A Research Study Investigating Mim8 in People With Haemophilia A (FRONTIER1). Last accessed June 2026. Available at: . ClinicalTrials.gov. A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors. Last accessed June 2026. Available at: . ClinicalTrials.gov. A Research Study Looking at Mim8 in Children With Haemophilia A With or Without Inhibitors. Last accessed June 2026. Available at: . ClinicalTrials.gov. A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People With Haemophilia A (FRONTIER 5). Last accessed June 2026. Available at: . Lentz S, Chowedary P, Gil L, et al. FRONTIER1: a partially randomized phase 2 study assessing the safety, pharmacokinetics, and pharmacodynamics of Mim8, a factor VIIIa mimetic. J Thromb Haemost. 2024;22(4): 990-1000. doi: 10.1016/j.jtha.2023.12.016 U.S. National Library of Medicine. F8 gene. MedlinePlus Genetics. Last accessed June 2026. Available at . Alhemo® (concizumab-mtci): Prescribing Information. 2024. Last accessed June 2026. Available at: . 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