Denecimig Well-Tolerated in Hemophilia A After Switching from Emicizumab

Results from the phase 3b FRONTIER5 trial demonstrate switching to denecimig (Mim8) from emicizumab can be done safely without a washout period or loading dose in patients with hemophilia A.

Announced on June 22, 2025, by parent company Novo Nordisk, the company also highlighted its intention to submit denecimig for US and EU regulatory review later this year. Data from the ongoing phase 3 FRONTIER program – including the studies FRONTIER, FRONTIER2, FRONTIER3, FRONTIER4, and FRONTIER5 – will be presented at upcoming conventions and publications in 2025 and 2026.1

“Continuous prophylactic coverage is critical to avoid breakthrough bleeds in people living with hemophilia; with new non-factor therapeutic options, many people could have hesitations about switching treatment options,” said Allison P. Wheeler, MD, Washington Center for Bleeding Disorders. “These data demonstrate that switching to Mim8 from emicizumab can be done without requiring a washout period. This is critical in ensuring that individuals maintain continuous protection against bleeding events as we seek to help address the ongoing needs of people living with this complex disease.”1

Denecimig, an investigational FVIIIa mimetic bispecific antibody, is designed to deliver once-monthly, once-every-2-weeks, or once-weekly prophylaxis for patients with hemophilia A. Given the defective clotting Factor VIII (FVIII), which causes hemophilia A, denecimig is administered subcutaneously and bridges Factor IXa and Factor X, which replaces FVII function to help restore the body’s thrombin generation capacity, which allows blood to clot.1

The FRONTIER5 study, a 26-week, open-label safety study, enrolled 61 adults and adolescents ≥12 years with hemophilia A. Investigators noted no thromboembolic events, treatment-emergent adverse events (TEAEs), or hypersensitivity reactions leading to discontinuation.2

Investigators also found no evidence of neutralizing anti-denecimig antibodies. Safety information from FRONTIER5 also demonstrated 107 TEAEs in 43 patients (70.5%) between Week 0 and Week 26 of treatment. Most of these were mild to moderate (88.6%), and only 24 were possibly related to denecimig reported in 18 (29.5%) patients.1

Additionally, patient-reported outcome data from FRONTIER5 noted overall (n = 57/59, 97%) patients preferred denecimig pen injections, with 97% reporting “very strong” or “fairly strong” preference in comparison to previous emicizumab injection systems.1

“The FRONTIER5 safety and patient-reported outcomes data support Mim8 as a potential future treatment option for people living with hemophilia A and demonstrate our continued commitment to developing innovative treatment options for the hemophilia community,” said Stephanie Seremetis, chief medical officer and CVP for rare disease at Novo Nordisk. “These results give valuable insights into hemophilia A management, highlight the feasibility of directly switching to Mim8 from emicizumab, and reveal a strong patient preference for the Mim8 pen-injector device.”1

References

1. Novo Nordisk. Mim8 prophylaxis treatment shown to be well-tolerated when switching from emicizumab in people with hemophilia A in new phase 3 data presented at the ISTH 2025 Congress. PR Newswire. June 22, 2025. Accessed June 23, 2025. https://www.prnewswire.com/news-releases/mim8-prophylaxis-treatment-shown-to-be-well-tolerated-when-switching-from-emicizumab-in-people-with-hemophilia-a-in-new-phase-3-data-presented-at-the-isth-2025-congress-302487467.html

2. Novo Nordisk. A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People with Haemophilia A (FRONTIER 5). ClinicalTrials.gov identifier: NCT05878938. Updated November 18, 2024. Accessed June 23, 2025. https://clinicaltrials.gov/study/NCT05878938