Mim8 Prophylaxis Tolerable for Children with Hemophilia A in Phase 3 Analysis

Johnny Mahlangu, BSc, MBBCh, MMed

Credit: ResearchGate

Interim analysis of the Phase 3 FRONTIERS3 trial reported the tolerability and efficacy of once-weekly Mim8 for children aged 1–11 years old living with hemophilia A with and without inhibitors.¹

Announced by Novo Nordisk, on February 7, 2025, these data, presented at the 18th Annual Congress of the European Association for Hemophilia and Allied Disorders (EAHAD), showed nearly three-quarters (74.3%) of children experienced zero treated bleeds with Mim8 prophylaxis.

“The FRONTIER3 interim analysis data are encouraging for families with young children and indicate that Mim8 could offer an efficacious, convenient, flexible dosing option for children, helping to reduce the treatment burden so families can live more normal lives,” said Johnny Mahlangu, BSc, MBBCh, MMed, director of the hemophilia comprehensive care center at Charlotte Maxeke Johannesburg Hospital at University of the Witwatersrand.¹

A rare inherited bleeding disorder impeding the body’s ability to make blood clots, hemophilia A is caused by a missing or defective clotting Factor VIII (FVIII). Estimates indicate more than 1 million people worldwide are affected by some form of hemophilia.² Mim8 is an investigational FVIIIa mimetic bispecific antibody designed to deliver sustained hemostasis once weekly, every 2 weeks, or monthly prophylaxis for people living with hemophilia A with and without inhibitors.

With subcutaneous administration, Mim8 is designed to bridge Factor IXa and Factor X, replacing FVIII and restoring thrombin generation capacity in the body. Comprised of two parts, FRONTIER3 assessed the efficacy and safety of Mim8 prophylaxis among 70 children with hemophilia A with inhibitors (n = 14) and without inhibitors (n = 56).¹

The first part of the trial assessed once-weekly subcutaneous Mim8 prophylaxis in all participants for 26 weeks. In the second part, participants could switch to Mim8 prophylaxis once-monthly or continue to receive once-weekly treatment, for the remaining 26 weeks.

This interim analysis from Novo Nordisk focused on results following part 1 of FRONTIERS3, with preliminary data shared from the trial’s ongoing part 2. Upon analysis, the estimated mean annualized bleeding rate (ABR) for treated bleeds was 0.53. The median ABR was zero with 74.3% experiencing zero treated bleeds.

All 14 children with hemophilia A with inhibitors reported zero treated bleeds. After the initial 26 weeks of study, 45% of participants moved to once-monthly Mim8, while the rest (55%) remained on the weekly dose. Participants and caregiver-reported outcomes data were also presented at the conference, suggesting Mim8 could reduce treatment burden and improve quality of life in children with hemophilia A with or without inhibitors.

At 26 weeks, nearly all (98%) caregivers preferred Mim8 to prior treatment, with 73% ‘very strongly’ preferring Mim8 more than other treatments. In the same period, improvement trends were identified in the mean physical function and quality of life scores, compared with baseline, in children with hemophilia A with or without inhibitors.

“Managing hemophilia A in young children can be a complex balancing act of delivering ongoing care, minimizing time out of school, and ensuring their physical, emotional and social wellbeing is optimized,” Mahlangu added.¹

Safety data from FRONTIERS3 showed no major safety concerns with Mim8, including death, thromboembolic events, severe treatment-emergent adverse events, or evidence of neutralizing anti-drug antibodies (ADAs). Injection site reactions were observed in ≤1% of all injections.

Novo Nordisk expects to submit Mim8 to regulatory authorities in 2025, with further plans to release data from the ongoing Phase 3 FRONTIER program at upcoming medical meetings.

“The FRONTIER3 data represent another step forward in our ambition to provide treatment options that place equal focus on safety and efficacy without requiring a compromise on treatment administration and quality of life,” said Ludovic Helfgott, executive vice president for Rare Disease at Novo Nordisk.¹ “Mim8 is designed with the aim to offer treatment flexibility based on individual lifestyles, so it is encouraging to see that patients and caregivers in these analyses prefer Mim8 over their previous treatment.”

References

1. _{Novo Nordisk A/S: Once-weekly Mim8 is well-tolerated and efficacious in children living with haemophilia A with and without inhibitors. Novo Nordisk. February 7, 2025. Accessed February 7, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915260.}
2. _{Mehta P, Reddivari AKR. Hemophilia. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551607/}