Denecimig (Mim8) Significantly Reduced Annualized Bleeding Rate in People with Hemophilia A, Regardless of Inhibitor Status, in Phase 3 Data Published in NEJM

PLAINSBORO, N.J. and BAGSVÆRD, Denmark — Today, the New England Journal of Medicine (NEJM) published 26-week results from the phase 3 FRONTIER2 trial evaluating the efficacy and safety of once-monthly and once-weekly denecimig (Mim8) in adults and adolescents 12 years of age and older with hemophilia A (congenital Factor VIII (FVIII) deficiency), with or without FVIII inhibitors. Investigational denecimig is a bispecific antibody Factor VIIIa (FVIIIa) mimetic, designed for routine prophylaxis to help the body form blood clots. It is being studied as part of the FRONTIER program across different dosing frequencies, age groups, and severities for people living with hemophilia A, with or without inhibitors.^1-7

“The prevention and reduction of bleeding episodes is the ultimate goal for people living with hemophilia A. These results from the FRONTIER2 study provide important data on the potential of denecimig as a preventive treatment option regardless of hemophilia A severity or inhibitor status,” said Dr. Maria Elisa Mancuso, Senior Consultant in Hematology at the Center for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital in Milan, Italy and lead investigator of the trial. “The publication of the FRONTIER2 study in NEJM demonstrates both the significance of these findings and how denecimig may help people living with hemophilia A.”

FRONTIER2 is a phase 3 clinical trial evaluating the efficacy and safety of denecimig for people with hemophilia A, with or without inhibitors. The study compared 254 adults and adolescents, 12 years and older, receiving once-monthly or once-weekly denecimig injections to those who received prior clotting factor prophylaxis treatment during the run-in phase or on-demand treatment.¹

The FRONTIER2 study measured how many bleeding episodes participants experienced each year that required treatment. People who received denecimig once-monthly had significantly fewer bleeding episodes compared to their previous treatments. Specifically, they experienced nearly 99% fewer bleeds compared to on-demand treatment, and about 43% fewer bleeds than when using their regular preventive clotting factor therapy.¹

Similarly, people who received denecimig once-weekly also had significantly fewer bleeding episodes. They experienced approximately 96% fewer bleeds compared to on-demand treatment, and about 54% fewer bleeds than with their previous preventive therapy.¹

In the four arms of the study, zero treated bleeds were reported in 64-95% of participants receiving denecimig, depending on the arm of the trial. In the comparator arms, zero treated bleeds were reported in 0-37% of participants depending on the arm (0% for the on-demand arm, 33% for pre-study clotting factor prophylaxis arm now on once-weekly denecimig treatment, and 37% for pre-study clotting factor prophylaxis arm now on once-monthly denecimig treatment).¹

“With denecimig recently submitted to the FDA through a Biologics License Application, these NEJM data further underscore its potential as a preventive treatment option that may help address the persistent unmet needs of people living with hemophilia A, with or without inhibitors,” said Anna Windle, PhD, Head of Clinical Development, Medical & Regulatory Affairs at Novo Nordisk US Operations. “The significant reductions in bleeding rates observed with denecimig demonstrate our commitment to developing innovative medicines with strong efficacy profiles and help lower treatment burden.”

In the study, denecimig was generally well-tolerated and no thromboembolic events or clinical evidence of neutralizing anti-denecimig antibodies were reported. Injection-site reactions (ISRs) were reported by 10% of participants, with ISRs observed for 2.6% of injections.¹

 

About Denecimig

Denecimig is an investigational FVIIIa mimetic bispecific antibody designed with the aim to deliver once-monthly, once-every-two-weeks, or once-weekly dosed prophylaxis for people living with hemophilia A, with or without inhibitors.^2-7 Denecimig, which is administered subcutaneously (under the skin), “mimics” the role of Factor VIIIa by bridging Factor IXa and Factor X.⁸ This action replaces FVIIIa function, which helps restore the body’s thrombin generation capacity, helping blood to clot.⁹ The use of denecimig in people living with hemophilia A, with or without inhibitors, is investigational and not approved by any regulatory authorities worldwide.

In September 2025, Novo Nordisk submitted denecimig for review to the US Food and Drug Administration (FDA) through a Biologics License Application (BLA), a formal request to evaluate a biologic medicine.

 

About Hemophilia A

Hemophilia is a rare inherited bleeding disorder that impairs the body’s ability to make blood clots, a process needed to stop bleeding.¹⁰ According to the World Federation of Hemophilia, it is estimated to affect approximately 836,000 people worldwide and hemophilia A is estimated to account for 80-85% of all hemophilia cases.¹¹ There are different types of hemophilia, which are characterized by the type of clotting factor protein that is defective or missing.⁵ Hemophilia A is caused by a missing or defective clotting Factor VIII (FVIII).⁸ Some people with hemophilia A may develop inhibitors, an immune system response to the clotting factors used in replacement therapy, which can cause treatment to become ineffective.¹² It has been estimated that approximately 30% of people living with hemophilia A have inhibitors.¹²

 

About the FRONTIER2 trial

FRONTIER2 is a phase 3 clinical trial evaluating the efficacy and safety of denecimig for people with hemophilia A, with or without inhibitors. The study compared 254 adults and adolescents, 12 years of age and older, receiving once-monthly or once-weekly denecimig injections to those who received prior clotting factor prophylaxis treatment during the run-in phase or on-demand treatment, with the primary endpoint being the mean ABR of treated bleeds.¹

Of the 254 patients, 246 patients completed the 26-week main phase. Four (2%) were female, 66 (26%) were adolescents (12-17 years of age), 212 (84%) had severe HA, and 31 (12%) had FVIII inhibitors.¹

The FRONTIER program includes FRONTIER1-5 and investigates denecimig as a preventive bleed treatment across pediatric and adult populations with hemophilia A, with or without inhibitors.^1-7

 

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 68,800 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.

 

Contacts for further information: 

 

References

1. Mancuso ME, Chan AKC, Shanmukhaiah C, et al. N Engl J Med. 2026;394:1696-1709. doi: 10.1056/NEJMoa2517384
2. ClinicalTrials.gov. A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors. Last accessed September 2025. Available at https://clinicaltrials.gov/study/NCT05053139.
3. ClinicalTrials.gov. A Research Study Looking at Mim8 in Children With Haemophilia A With or Without Inhibitors. Last accessed September 2025. Available at https://clinicaltrials.gov/study/NCT05306418.
4. ClinicalTrials.gov. A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER 4). Last accessed September 2025. Available at https://clinicaltrials.gov/study/NCT05685238.
5. Østergaard H, Lund J, Greisen PJ, et al. A factor VIIIa-mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice. Blood. 2021;138(14):1258-1268. doi: 10.1182/blood.2020010331
6. ClinicalTrials.gov. A Research Study Investigating Mim8 in People With Haemophilia A (FRONTIER1). Last accessed September 2025. Available at https://clinicaltrials.gov/study/NCT04204408.
7. 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 September 2025. Available at https://clinicaltrials.gov/study/NCT05878938.
8. 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
9. U.S. National Library of Medicine. F8 gene. MedlinePlus Genetics. Last accessed August 2025. Available at https://medlineplus.gov/genetics/gene/f8/.
10. MedlinePlus. Hemophilia. Last accessed September 2025. Available at https://medlineplus.gov/genetics/condition/hemophilia.
11. World Federation of Hemophilia. World Federation of Hemophilia Report on the Annual Global Survey 2023. Last accessed September 2025. Available at https://wfh.org/research-and-data-collection/annual-global-survey/.
12. Kim JY, You CW. The prevalence and risk factors of inhibitor development of FVIII in previously treated patients with hemophilia A. Blood Res. 2019;54:204-209. doi: 10.5045/br.2019.54.3.204