Switching from Emicizumab to Mim8 Without a Washout Period Is Safe and Well-Tolerated in Hemophilia A Patients

A new global trial shows that patients with hemophilia A can safely switch from Hemlibra (emicizumab) to investigational Mim8 prophylaxis without needing a washout period or loading dose, according to results from the phase 3b FRONTIER5 study presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress.

Mim8 (denecimig) is an investigational therapy being developed by Novo Nordisk as a long-acting, under-the-skin treatment for people with hemophilia A, including those with inhibitors.

Similar to emicizumab, Mim8 mimics the function of clotting Factor VIII (FVIII) protein, which is missing or defective in people with hemophilia A.

The goal is to support blood clotting and prevent spontaneous or injury-related bleeds.

Hemophilia A is a rare inherited bleeding disorder that affects the body’s ability to form blood clots due to a deficiency in FVIII.

It’s the most common form of hemophilia, affecting approximately 1 in 5,000 male births globally.

People with severe hemophilia A are at risk of life-threatening bleeds, and up to 30% develop inhibitors—immune responses that block the effect of replacement therapies, making treatment more complex.

Mim8 offers the potential for once-weekly, every-two-week, or once-monthly prophylactic dosing.

It acts by bridging activated Factor IX and Factor X proteins, which then restore thrombin generation and support the formation of stable blood clots.

The drug is still under investigation and not yet approved by any regulatory agency.

Hemophilia A is a rare inherited bleeding disorder that affects the body’s ability to form blood clots due to a deficiency in FVIII protein.

In the FRONTIER5 trial, 61 participants aged 12 and older who were previously treated with emicizumab transitioned directly to Mim8 without any washout period.

It’s crucial to note, the switch was well tolerated: no thromboembolic events, hypersensitivity reactions, or treatment-emergent adverse events (TEAEs) leading to discontinuation were reported.

Between week 0 and week 26 of treatment, a total of 107 TEAEs were reported among 43 participants (70.5%). Most adverse events (88.6%) were mild or moderate in severity.

It was found that only 24 events in 18 patients (29.5%) were deemed possibly or probably related to Mim8 treatment.

"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," Allison P. Wheeler, M.D., scientific director of the Washington Center for Bleeding Disorders, said in the release. “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 addition to safety outcomes, patient-reported outcomes (PROs) from the trial revealed high satisfaction with the Mim8 pen-injector device.

According to the Hemophilia Device Handling and Preference Assessment (HDHPA), 97% of participants (57 out of 59) preferred the Mim8 pen to their previous emicizumab injection method, and 98% found it easy or very easy to use.

It was also found that 95% said it was easier or much easier to use compared to their prior treatment method. Every participant reported feeling either “very confident” or “extremely confident” using the pen correctly.

"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."

The FRONTIER clinical program includes five phase 3 trials (FRONTIER1 through FRONTIER5) evaluating Mim8 as a prophylaxis treatment for individuals with hemophilia A, regardless of inhibitor status.

Novo Nordisk plans to submit Mim8 for regulatory review in the U.S. and Europe in 2025, with additional data expected from the ongoing program in 2025 and 2026.

If approved, Mim8 could offer people with hemophilia A a flexible and effective alternative to current prophylactic treatments—while maintaining continuous protection and simplifying the injection process.