Directly switching from Hemlibra to investigational Mim8 well tolerated
Study participants found device for administering therapy easy to use
Directly switching from Hemlibra (emicizumab) to Novo Nordisk‘s investigational Mim8 (denecimig) was well tolerated in adults and adolescents with hemophilia A, regardless of whether they had inhibitors or not.
That’s according to results from the now-completed Phase 3b FRONTIER5 study (NCT05878938), which assessed the safety of switching between the two preventive therapies without a washout period or a Mim8 loading dose in 61 people 12 years and older with hemophilia.
Study participants said the injector pen device used to administer Mim8 subcutaneously, or under the skin, was easy to use, with strong user preference over their previous injection system.
“The FRONTIER5 safety and patient-reported outcomes data support Mim8 as a potential future treatment option for people living with hemophilia A,” Stephanie Seremetis, MD, chief medical officer and corporate vice president for rare disease at Novo Nordisk, said in a company press release. “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.”
Data were reported in a presentation, titled “FRONTIER5 direct switch study: Safety of initiating Mim8 prophylaxis without washout of emicizumab,” at the International Society on Thrombosis and Haemostasis Congress, being held in Washington, D.C.
Mim8 mimics clotting factor’s function
Hemophilia A is caused by a missing or defective clotting factor VIII (FVIII), leading to prolonged bleeding episodes that can be hard to control.
Standard hemophilia A treatment usually includes factor replacement therapies, which provide patients with a functional FVIII to control or prevent bleeding episodes. Still, some patients develop antibodies, or inhibitors, against the lab-made clotting factor, which can limit the treatment’s effectiveness.
Mim8 is an antibody-based therapy designed to mimic the function of FVIII by stimulating the production of thrombin, an enzyme that helps blood to clot. Because it does not involve FVIII directly, Mim8 can be administered to people with inhibitors.
The FRONTIER 1 Phase 2 trial (NCT04204408), which evaluated Mim8 in healthy volunteers and hemophilia A patients, showed early positive results, with most patients given higher doses experiencing no bleeds during treatment.
These findings supported the launch of several Phase 3 trials, including FRONTIER 2 (NCT05053139), which showed Mim8 was better than on-demand or standard preventive treatments at reducing bleeding episodes in hemophilia A patients, regardless of inhibitor status. Mim8 was also well tolerated and provided effective bleed control in children with hemophilia A.
“Continuous [preventive] 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,” Allison P. Wheeler, MD, of the Washington Center for Bleeding Disorders in Seattle, said in the press release.
Therapy yields sustained increase in key enzyme
The open-label Phase 3 FRONTIER5 safety study enrolled 61 adults and adolescents 12 years and older with hemophilia A who had previously received Hemlibra. All participants were switched directly to Mim8 without a washout period or a loading dose.
Mim8 was given using a prefilled pen-injector weekly, every two weeks, or monthly, depending on patient preference and discussions with the investigator, for 26 weeks, or about six months.
Over the study period, switching to Mim8 provided a sustained increase in thrombin into the normal range, without an exaggerated response.
No adverse blood-clotting events, hypersensitivity reactions, or treatment-emergent adverse events (TEAEs) led to treatment discontinuation, and there was no evidence of inhibitors against Mim8. Overall, there were 107 TEAEs reported in 43 patients (70.5%), most of which were mild to moderate (88.6%). Of these, 24 were possibly/probably related to Mim8 reported in 18 patients (29.5%).
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.
In patient-reported outcomes, nearly all patients (97%) preferred the Mim8 pen injection, with almost all of those patients (97%) reporting a “very strong” or “fairly strong” preference over their previous Hemlibra injections.
Of those who completed the Hemophilia Device Handling and Preference Assessment questionnaire, 98% found the Mim8 pen-injector “very easy” or “easy” to use, and 95% found it “much easier” or “easier” compared with their previous treatment method. All participants were “extremely confident” or “very confident” about using the pen-injector correctly.
“These data demonstrate that switching to Mim8 from emicizumab can be done without requiring a washout period,” Wheeler said. “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.”
The company plans to submit an application seeking approval for Mim8 in the U.S. and European Union this year. Data from the ongoing Phase 3 FRONTIER program will be reported at upcoming congresses and publications this year and in 2026, according to Novo Nordisk.
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