LB 01.5 - Efficacy and safety of Mim8 prophylaxis in adults and adolescents with hemophilia A with or without inhibitors: Phase 3, open-label, randomized, controlled FRONTIER2 study

Sunday, June 23, 2024

10:30 – 10:45 ICT

Room: Plenary Hall

Presenting Author(s)

Maria Elisa Mancuso, MD, PhD

Senior Consultant in Haematology
Centre for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital
Milan, Lombardia, Italy

Co-Author(s)

Tadashi Matsushita

Professor
Nagoya University Hospital, Nagoya, Japan
Nagoya, Aichi, Japan
Pratima Chowdary, MD

Professor of Haemophilia, Centre Director
Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital
London, England, United Kingdom
SL

Steven R. Lentz

Professor of Internal Medicine, Henry Hamilton Chair in Hematology
The University of Iowa Carver College of Medicine
Iowa City, Iowa, United States
Johnny Mahlangu, MBBCh, MMed

Head of Department and Principal Haematologist
Department of Molecular Medicine and Haematology, University of the Witwatersrand, National Health Laboratory Service, and Charlotte Maxeke Johannesburg Academic Hospital
Johannesburg, Gauteng, South Africa
CS

Chandrakala Shanmukhaiah

Professor
Department of Clinical Hematology, Seth G.S.M.C and K.E.M. Hospital
Mumbai, Maharashtra, India
IR

Ilgiz Rakhmatullin

Senior International Medical Manager
Novo Nordisk A/S
Bagsværd, Hovedstaden, Denmark
PJ

Pernille Juul Jørgensen

Senior Statistician
Novo Nordisk A/S
Bagsværd, Hovedstaden, Denmark
Johannes Oldenburg, MD

Professor, Chairman and Director
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine
Bonn, Nordrhein-Westfalen, Germany

Background: Mim8 (denecimig) is a factor VIIIa mimetic bispecific antibody in clinical development for subcutaneous prophylaxis in hemophilia A (HA).

Aims: Evaluate the efficacy and safety of Mim8 in males and females (aged ≥12 years) with HA with or without inhibitors.

Methods: FRONTIER2 (NCT05053139) is a phase 3, open-label, randomized, controlled study. Mim8 was administered using tiered dosing (Figure 1). Primary objectives: demonstrate the hemostatic effect of Mim8 once-every-week (QW) and once-every-month (QM) at week 26 versus either on-demand treatment, or versus previous clotting factor concentrate (CFC) prophylaxis during the run-in period. Annualized bleeding rate (ABR) was estimated using a negative binomial regression model. Safety and immunogenicity were evaluated. Study was conducted following informed consent and ethical approval.

Results: Overall, 254 patients were randomized (Table 1). In patients previously treated on-demand, estimated mean ABR [95% CI] for treated bleeds was 0.45 [0.18;1.14] for QW and 0.20 [0.06;0.72] for QM Mim8 prophylaxis, versus 15.75 [10.7;23.2] for continued on-demand treatment (Table 1). Mim8 prophylaxis was superior to on-demand treatment, with ABR reduction of 97.1% (QW) and 98.7% (QM).

In patients on pre-study CFC prophylaxis, estimated mean ABR for treated bleeds was 2.51 [1.42;4.42] for QW and 1.78 [1.17;2.71] for QM Mim8 prophylaxis, versus 4.83 [3.59;6.51] and 3.10 [2.23;4.29], during run-in CFC prophylaxis, respectively (Table 1). Mim8 prophylaxis was superior to run-in CFC prophylaxis, with ABR reduction of 48.0% (QW) and 42.6% (QM).

Zero bleeds were observed in 65.3–95.0% of patients treated with Mim8 (Table 1). Injection-site reactions occurred in 5.0–12.2% of patients. There were no safety concerns and no clinical evidence of neutralizing anti-Mim8 antibodies.

Conclusion(s): FRONTIER2 demonstrated superiority of Mim8 prophylaxis once-every-week and once-every-month in reducing ABR for treated bleeds compared with either on-demand treatment or clotting factor concentrate prophylaxis. Mim8 was well tolerated, and no safety concerns were observed.

Funded by Novo Nordisk.