Novo's denecimig demonstrates tolerability after switch from emicizumab in FRONTIER5 study of people with hemophilia A as published in the Journal of Thrombosis and Haemostasis

• FRONTIER5 data show investigational denecimig was well-tolerated with no unforeseen safety concerns after a direct switch from emicizumab, without the need for a washout period or loading dose, in people with hemophilia A aged 12 and older with or without inhibitors¹
• Most patients reported the denecimig pen injector easy to use compared to their previous emicizumab vial and syringe system, as measured by a device questionnaire¹
• Denecimig increased thrombin generation, a measure of blood clotting function, to levels in the normal range throughout the study period as an exploratory endpoint, without causing any excessive clotting¹ 

PLAINSBORO, N.J. and BAGSVÆRD, Denmark, Sept. 17, 2026 /PRNewswire/ -- Novo Nordisk today announced that phase 3b results from the FRONTIER5 study of investigational denecimig were published in the Journal of Thrombosis and Haemostasis. The 26-week results showed that a direct switch to the subcutaneous denecimig pen injector from the emicizumab vial and syringe injection system, without a washout period or a denecimig loading dose, was well tolerated with no unforeseen safety concerns in adolescents and adults living with hemophilia A (congenital factor VIII deficiency) with or without inhibitors. Compared to their previous emicizumab vial and syringe system, most patients preferred the denecimig pen injector and found it easier to use, as measured by the Hemophilia Device Handling and Preference Assessment (HDHPA) as a supportive secondary endpoint. Additionally, exploratory results showed thrombin peak height increased into the normal range and was sustained over 26 weeks, with no clinical evidence of excessive clotting observed after the switch from emicizumab to denecimig across all dosing frequencies.

"What stands out from the published phase 3b data is the well-tolerated switch to denecimig along with the sustained increase in thrombin generation into the normal range," said Stephanie Seremetis, Chief Medical Officer and CVP for Rare Disease at Novo. "The positive device handling data and majority preference for our injection pen was equally encouraging, and a testament to Novo's intentional design process with the goal of providing this patient population additional options for administration."

In the open-label phase 3b FRONTIER5 safety study, 61 adults and adolescents aged 12 years and older with hemophilia A, with or without inhibitors, were enrolled and completed the 26-week treatment period. The primary safety endpoint of the study found that between Week 0 and Week 26 of treatment, there were 107 treatment-emergent adverse events (TEAEs) observed in 43 patients (70.5%), most of which were mild to moderate (98.1%). There were 24 TEAEs that were possibly/probably related to denecimig. Denecimig safety was found to be consistent with findings previously shared from the FRONTIER research program. No thromboembolic events, hypersensitivity reactions, or TEAEs leading to discontinuation were observed, and there was no clinical evidence of neutralizing anti-denecimig antibodies.¹ 

Hemophilia A is a rare, inherited bleeding disorder where a deficiency in clotting factor VIII hinders thrombin production, impairing the body's ability to make blood clots and stop bleeding.² A Biologics License Application (BLA) is currently under review with the US Food and Drug Administration (FDA) for denecimig as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A, with or without inhibitors, in once-weekly, once-every-two-weeks, or once-monthly dosing frequencies.

"Switching to a new hemophilia treatment typically requires careful spacing between treatments to avoid creating a combined, additive effect on thrombin generation," said Allison P. Wheeler, MD, University of Colorado School of Medicine, Aurora CO. "Additionally, that transition period requires close monitoring and coordination to manage gaps in protection that could increase the risk of breakthrough bleeding. Crucially, patients in the FRONTIER5 study were able to safely switch directly to denecimig without waiting until emicizumab is completely cleared from their system, and without needing an initial loading dose to jump-start their new regimen."

A supportive secondary endpoint studied among 59 of the 61 enrolled patients showed most participants (98.3%) rated the denecimig injection pen as "easy" or "very easy" to use (Hemophilia Device Handling and Preference Assessment, HDHPA). Most patients (94.9%) reported that the denecimig injection pen was easier to use overall than their previous administration method and most patients (96.6%) preferred the denecimig injection pen to the previous administration method. Responses were similar across each dosage frequency. See the table below for additional data.¹

An additional supportive secondary endpoint studied in 55 of the 61 enrolled patients found denecimig reduced treatment burden by an average (standard deviation [SD]) of 4.7 points (9.0) at week 26, from a baseline total score of 10.5 (10.2), based on the Hemophilia Treatment Experience Measure (Hemo-TEM). See the table below for additional data.¹

Data from an exploratory objective of FRONTIER5 showed denecimig increased thrombin generation, a measure of blood clotting function, to levels in the normal range after switching from emicizumab. The increase was sustained over the 26-week study period without any clinical evidence of synergistic thrombin peak height effect or excessive clotting across all dosing frequencies. Denecimig also reached steady-state plasma concentrations by week 16 without a loading dose. See the table below for additional data.¹

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.² According to the World Federation of Hemophilia's Annual Global Survey 2024, hemophilia is estimated to affect approximately 836,000 people worldwide and hemophilia A is estimated to account for 80-85% of all hemophilia cases.³ There are different types of hemophilia, which are characterized by the type of clotting factor protein that is defective or missing.⁴ Hemophilia A is caused by a missing or defective clotting Factor VIII (FVIII).⁵ 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.⁶ It has been estimated that approximately 30% of people living with hemophilia A will develop inhibitors.⁶

About investigational 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.^7-11 Intended to be administered under the skin in a single-dose, prefilled disposable pen, denecimig bridges Factor IXa and Factor X.¹² This action mimics FVIIIa function, which helps restore the body's thrombin generation capacity, helping blood to clot.¹³

About the FRONTIER Clinical Program
The FRONTIER clinical program includes FRONTIER1-5 and investigates denecimig as a prophylactic treatment for adults, adolescents, and children with hemophilia A, with or without inhibitors.^7-11

The phase 1/2 FRONTIER1 study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of denecimig for adolescents and adults aged 12 and older living with hemophilia A, with or without inhibitors. FRONTIER2 compared the efficacy and safety of once-monthly and once-weekly denecimig versus on-demand bypassing agent or clotting factor treatment and versus prior prophylactic treatment in people aged 12 and older living with hemophilia A, with or without inhibitors. FRONTIER3 evaluated the safety and efficacy of once-monthly and once-weekly denecimig treatment in children below the age of 12 who were previously untreated or previously treated with prophylaxis, on-demand bypassing agent, or clotting factor treatment for hemophilia A, with or without inhibitors. FRONTIER4 is an ongoing extension study following patients who chose to continue denecimig treatment after participating in prior FRONTIER studies. The ongoing study evaluates the long-term safety and efficacy of denecimig across once-weekly, once-every-two-weeks, and once-monthly dosing in hemophilia A participants of all ages and disease severities, with or without inhibitors. The phase 3b FRONTIER5 study investigated the safety of switching from emicizumab, an existing hemophilia A treatment, to denecimig without a washout period or loading dose in adolescents and adults aged 12 and older living with hemophilia A with or without inhibitors.^1,7-11,14

Novo is the global healthcare company that believes lasting health starts now. For over a century, we've combined leading scientific expertise with a deep understanding of people's lives. We develop treatments and support that help millions of people make progress they can see, feel and sustain now and in the future. Through our partnerships, programs and investments, we're working to prevent disease, expand access to treatments and reduce our environmental impact to help even more people live healthier lives. In the United States, Novo 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.  For more information, visit novonordisk-us.com and follow us on Instagram, LinkedIn, TikTok, Facebook, X and YouTube.

Contacts for further information

References

1. Hermans C, Benson G, Matino D, et al. FRONTIER5: Safety and patient experience of a direct switch from emicizumab to denecimig (Mim8) in patients with haemophilia A with or without inhibitors. J Thromb Haemost. Published online September 11, 2026. doi: 10.1016/j.jtha.2026.09.004.
2. Salen P, Babiker HM. Hemophilia A. 2023. StatPearls Publishing. PMID: 29261993.
3. World Federation of Hemophilia. World Federation of Hemophilia Report on the Annual Global Survey 2024. Last accessed September 2026. Available at https://wfh.org/research-and-data-collection/annual-global-survey/.
4. 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
5. 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
6. 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
7. Clinicaltrials.gov. A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER 4). Last accessed September 2026. Available at: https://clinicaltrials.gov/study/NCT05685238.
8. ClinicalTrials.gov. A Research Study Investigating Mim8 in People With Haemophilia A (FRONTIER1). Last accessed September 2026. Available at: https://clinicaltrials.gov/study/NCT04204408.
9. ClinicalTrials.gov. A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors. Last accessed September 2026. Available at: https://clinicaltrials.gov/study/NCT05053139.
10. ClinicalTrials.gov. A Research Study Looking at Mim8 in Children With Haemophilia A With or Without Inhibitors. Last accessed September 2026. Available at: https://clinicaltrials.gov/study/NCT05306418.
11. 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 2026. Available at: https://clinicaltrials.gov/study/NCT05878938.
12. 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
13. U.S. National Library of Medicine. F8 gene. MedlinePlus Genetics. Last accessed September 2026. Available at https://medlineplus.gov/genetics/gene/f8/.
14. 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.

SOURCE Novo Nordisk