Novo Nordisk presented promising results from its phase 3b FRONTIER5 trial at the International Society on Thrombosis and Haemostasis (ISTH) Congress in Washington, D.C., demonstrating that patients with hemophilia A can safely transition directly from emicizumab to investigational Mim8 (denecimig) prophylaxis treatment without requiring a washout period.
Trial Design and Patient Population
The open-label FRONTIER5 study enrolled 61 adults and adolescents aged 12 years and older with hemophilia A, with or without inhibitors. The 26-week trial evaluated the safety of switching from previous emicizumab prophylaxis treatment directly to Mim8 prophylaxis using the Mim8 pen-injector.
In the study protocol, 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.
Safety Profile and Clinical Outcomes
The trial demonstrated a favorable safety profile with no significant concerns. Between Week 0 and Week 26 of treatment, there were 107 treatment-emergent adverse events (TEAEs) observed in 43 patients (70.5%), with most being mild to moderate (88.6%). Twenty-four TEAEs were possibly or probably related to Mim8, reported in 18 patients (29.5%).
Critically, no thromboembolic events, hypersensitivity reactions, or treatment-emergent adverse events leading to discontinuation were observed. Additionally, there was no clinical evidence of neutralizing anti-Mim8 antibodies.
The pharmacokinetic data showed that steady-state Mim8 concentration was achieved by Week 16, and emicizumab elimination was completed by Week 26. Switching to Mim8 led to a sustained increase in thrombin peak levels without an exaggerated thrombin response, bringing thrombin generation into the normal range without posing thrombotic risk.
Patient-Reported Outcomes and Device Preference
The FRONTIER5 Patient-Reported Outcomes assessment revealed strong patient preference for the Mim8 delivery system. Of patients who completed the Hemophilia Device Handling and Preference Assessment (HDHPA) questionnaire at week 26, 97% (n=57/59) reported a "very strong" or "fairly strong" preference for the Mim8 pen-injector compared to their previous emicizumab injection system.
Device usability metrics were equally impressive: 98% (n=58/59) found the Mim8 pen-injector "very easy" or "easy" to use, and 95% (n=56/59) found it "much easier" or "easier" compared with their previous administration method. All participants (100%) were "extremely confident" or "very confident" in using the pen-injector correctly, and 83% (n=49/59) found it "very easy" to inject the dose.
Clinical Significance and Expert Perspective
"Continuous prophylactic coverage is critical to avoiding 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, from the Washington Center for Bleeding Disorders in Seattle. "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."
About Mim8 and Hemophilia A
Mim8 is an investigational FVIIIa mimetic bispecific antibody designed to deliver flexible dosing intervals up to once-monthly prophylaxis for people living with hemophilia A, with or without inhibitors. Administered subcutaneously, Mim8 bridges Factor IXa and Factor X, replacing FVIII function and helping restore the body's thrombin generation capacity to help blood clot.
Hemophilia A, caused by missing or defective clotting Factor VIII, affects approximately 1,125,000 people worldwide. Up to 30% of people living with severe hemophilia A develop inhibitors that can cause replacement therapies to stop working, representing a significant unmet medical need.
Regulatory Timeline and Future Development
Stephanie Seremetis, Chief Medical Officer and CVP for Rare Disease at Novo Nordisk, stated: "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."
Novo Nordisk plans to submit Mim8 for U.S. and EU regulatory review during 2025. The company expects to disclose additional data from the ongoing phase 3 FRONTIER program at upcoming congresses and in publications throughout 2025 and 2026.
The FRONTIER clinical program investigating Mim8 as prophylaxis treatment includes five studies: FRONTIER1, FRONTIER2, FRONTIER3, FRONTIER4, and FRONTIER5, comprehensively evaluating the therapy across different patient populations and treatment scenarios.
