Mim8 (denecimig) prophylaxis was well-tolerated in FRONTIER5 phase 3 switch trial in people with haemophilia A

• New FRONTIER5 data shows direct switch to Mim8 prophylaxis treatment from emicizumab without need for a washout period was generally well-tolerated in adults and adolescents with haemophilia A, with or without inhibitors¹.
• Patient feedback gathered during the trial showed an overall preference for the Mim8 subcutaneous pen-injector over their previous injection device².
• These results, presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in Washington, add to the overall clinical findings for Mim8 based on the FRONTIER clinical trial programme³.

GATWICK, UK, June 22, 2025 – Novo Nordisk today presented data that showed a direct switch to Mim8 (denecimig) prophylaxis treatment from emicizumab without a need for a washout period was generally well-tolerated in people with haemophilia A with or without inhibitors^1,2.

The results, presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in Washington, D.C., follow the phase 3 FRONTIER5 trial of 61 adults and adolescents aged 12 years and older with haemophilia A.^1,2.

The trial assessed the safety of the investigational treatment, Mim8 prophylaxis, following a direct switch from emicizumab treatment, without a washout period or loading dose. The first Mim8 maintenance dose was administered on the next planned emicizumab dosing day.

Patients were given the option of switching to once-monthly, once every two weeks or once-weekly dosing frequencies of Mim8, regardless of their prior dosing frequency^1,3. The trial also assessed the  pen-injector handling experience and patient preference, alongside other Patient-Reported Outcomes (PROs)^2,3.

The data showed a safety profile consistent with previous findings from FRONTIER phase 3 trials. There was no evidence of antibodies neutralising the effect of Mim8 and the steady-state concentration was observed by Week 16. Emicizumab had been cleared from the body by Week 26¹. No exaggerated thrombin peak height response was observed in switching to Mim8.

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 (88.6%) in patients taking Mim8. There were 24 TEAEs that were possibly/probably related to Mim8 reported in 18 patients (29.5%); there were no serious adverse events related to  Mim8 therapy¹. No thromboembolic events, hypersensitivity reactions, or TEAEs leading to discontinuation were observed¹.  

"Rare diseases such as haemophilia have a profound impact on the lives of those who live with them. This is why we must continue our mission to drive change to defeat them.” said Sebnem Avsar Tuna, UK General Manager, Novo Nordisk. "We believe ongoing research and additional treatment options are important to further support those with haemophilia to live with fewer limitations.”

The patient reported outcome (PRO) data from FRONTIER5 indicated an overall user preference (97%; n=57/59) for the Mim8 pen-injector over their previous injection system. Of the participants who completed the Haemophilia Device Handling and Preference Assessment (HDHPA) questionnaire at week 26, 98% (n=58/59) found the Mim8 subcutaneous pen-injector “very easy” or “easy” to use, and 95% (n=56/59) found it “much easier” or “easier” compared with their previous administration method².

All participants (100%) were “extremely confident” or “very confident” in using the pen-injector correctly, and most participants (83%; n=49/59) found it “very easy” to inject the dose.

Novo Nordisk expects to submit Mim8 for UK regulatory review in 2026.

About haemophilia

Haemophilia is a rare inherited bleeding disorder that impairs the body’s ability to make blood clots, a process needed to stop bleeding⁵. It is estimated to affect approximately 1,125,000 people worldwide⁶. There are different types of haemophilia, which are characterised by the type of clotting factor protein that is defective or missing⁵. Haemophilia A is caused by a missing or defective clotting Factor VIII (FVIII), and haemophilia B is caused by a missing or defective clotting Factor IX⁷. Inhibitors are an immune system response to the clotting factors in replacement therapy. Currently, it is estimated that up to 30% of people living with severe haemophilia A have inhibitors that can cause replacement therapies to stop working⁴.

About Mim8

Mim8 (denecimig) is an investigational FVIIIa mimetic bispecific antibody designed with the aim to deliver sustained hemostasis for once-monthly, once-every-two-weeks, or once-weekly prophylaxis for people living with haemophilia A, with or without inhibitors⁷. Administered under the skin, it bridges Factor IXa and Factor X. This action replaces FVIII function, which restores the body’s thrombin generation capacity, helping blood to clot^7,8. The use of Mim8 in people living with haemophilia A is investigational and not approved by regulatory authorities or available anywhere in the world.

About the FRONTIER5 trial

FRONTIER5 is a single-arm, open-label, 26-week, phase 3b trial evaluating the safety of switching from previous emicizumab prophylaxis treatment directly to Mim8 prophylaxis treatment using the Mim8 pen-injector in adults and adolescents with haemophilia A, with or without inhibitors³.

The FRONTIER clinical programme investigates Mim8 as a prophylaxis treatment for people with haemophilia A, with or without inhibitors. The phase 3 programme includes FRONTIER2⁹, FRONTIER3¹⁰, FRONTIER4¹¹, and FRONTIER5³.

About Novo Nordisk
Novo Nordisk is a leading global healthcare company founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 76,300 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.co.uk.

References

1.         Oldenberg J, Benson G, Chowdaryet P, et al. FRONTIER5 direct switch study: Safety of initiating Mim8 prophylaxis without washout of emicizumab. Oral presentation presented at the Congress of the International Society on Thrombosis and Haemostasis 2025; June 21-25 2025; Walter E. Washington Convention Center, Washington D.C., US. Session code 13686. 

2.         Mahlangu J, Ahuja S, Cockrell E, et al. Evaluating pen-injector handling and PROs in patients switching from emicizumab to Mim8 in FRONTIER5. Oral presentation presented at the Congress of the International Society on Thrombosis and Haemostasis 2025; June 21–25 2025; Walter E. Washington Convention Center, Washington D.C., US. Session code 13786.

3.         ClinicalTrials.gov. A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People With Haemophilia A (FRONTIER5). Available at: https://clinicaltrials.gov/study/NCT05878938 Last accessed: April 2025.

4.         Kim JY, You CW. The prevalence and risk factors of inhibitor development of FVIII in previously treated patients with haemophilia A. Blood Res. 2019;54:204-209. doi: 10.5045/br.2019.54.3.204

5.         MedlinePlus. Haemophilia. Available at: https://medlineplus.gov/genetics/condition/haemophilia. Last accessed: April 2025. .

6.         Iorio A, Stonebraker JS, Chambost H, et al. Establishing the Prevalence and Prevalence at Birth of Haemophilia in Males: A Meta-analytic Approach Using National Registries. Ann Intern Med. 2019;171:540-546. doi: 10.7326/M19-1208

7.         Ostergaard H, Lund J, Greisen PJ, et al. A factor VIIIa-mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in haemophilia A mice. Blood. 2021;138:1258-1268. doi: 10.1182/blood.2020010331

8.         U.S. National Library of Medicine. F8 gene. MedlinePlus Genetics. Available at: https://medlineplus.gov/genetics/gene/f8/ Last accessed: April 2025.

9.         ClinicalTrials.gov. A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors. Available at: https://clinicaltrials.gov/study/NCT05053139 Last accessed: April 2025.

10.       ClinicalTrials.gov. A Research Study Looking at Mim8 in Children With Haemophilia A With or Without Inhibitors. Available at: https://clinicaltrials.gov/study/NCT05306418 Last accessed: April 2025.

11.       ClinicalTrials.gov. A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER4). Available at: https://clinicaltrials.gov/study/NCT05685238 Last accessed: April 2025.